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What Big Pharma

doesnt want you

to know
Part one:
Dangerous drugs
Over-the-counter drugs
2 OTC drugs: medicines dark side
7 Death by aspirin

Drugs for depression

11 The great depression myth
15 The great Prozac conspiracy
19 SSRIs: bad prescribing habits
21 SSRIs: discontinuation syndrome

Drugs for children

23 Kiddie killers
28 Puffers get blown out
29 The kiddie upper takes tumble

31 Life after antibiotics
35 Antibiotics: definitely not kids stuff
A Drug-induced disease

Medicine and the elderly
The damaged brain: how drugs cause dementia
Anticholinergic drugs: the stupid pills
Diabetes: epidemic by prescription
51 HRT: the latest cancer risk
52 The big cure-all unmasked

Over-the-counter drugs

OTC drugs: medicines dark side

Over-the-counter OTC sleeping pills, to which he had
remedies are thought become addicted.
Tragically, many hundreds of
to be safe because they thousands of people suffer the same
can be easily purchased fate as Heath Ledger every year as a
from pharmacies and direct result of an OTC drugbut their
deaths are never recorded as such
stores, but its an
because there is no monitoring system
unregulatedand in place.
boomingmarket of Researchers at the Eastern Virginia
medications that can be Medical School reckon that OTC pain-
killers that contain aspirin are, on their
every bit as dangerous own, responsible for 20,000 deaths and
as prescription drugs 100,000 hospitalizations every year in
the US. Yet, not only are these drugs
TC, or over-the-counter, never suspected of being the cause, but

O drugsremedies that you

can buy in pharmacies
and stores without a
prescriptionare the dark side of
medicine. Many of the active agents in
most patients who need hospital care
dont even bother to mention that they
were taking such drugs as aspirinso
harmless are OTC drugs thought to be.
As the lead researcher and gastro-
active ingredients, such as codeine,
that have never been subjected to any
rigorous safety tests. In the UK, a
regulatory framework for OTC drugs
came into existence only in 1971
the OTC drugs that are sold every day enterologist of the above report, Dr and, in the US, in 1962so any active
have never passed any safety trials, so David Johnson, has said: This reflects compound that was introduced before
no one knows what happens to a common misperception that these those dates has never been tested. This
consumers once they walk out of medications are insignificant or benign means that agents such as aspirin,
the store with their medications. when actually their chronic use, codeine, dextromethorphan (DXM),
There are more than 100,000 particularly among the elderly and in paracetamol (acetaminophen in the
different OTC remedies available for those with conditions such as arthritis, US) and diphenhydramine have never
us to self-medicate a range of common is linked to serious and potentially passed any proper safety trials, and yet
ailmentsincluding migraine head- fatal GI [gastrointestinal] injury and they are found in many popular
aches, insomnia, stomach pain and bleeding (Proceedings of the Annual Scien- household OTC brands such as Alka-
indigestion problems, arthritis, general tific Meeting of the American College of Gastro- Seltzer, Calpol, Tylenol and Vicks.
aches and pains, and coughs and enterology, October 15, 2007, Philadelphia, PA).
coldsas well as products to help us In fact, millions of people may well Double trouble
lose weight and stop smoking. be addicted to OTC drugs, especially The OTC market has been earmarked
Because we can walk into any high- those that contain codeine, which is a as the next major happy-hunting
street pharmacy or chemist and buy controlled substance derived from ground of pharmaceutical companies.
them with a minimum of fuss and opium. However, its a major social Over the next few years, we are likely
questions asked, we believe they are problem that remains invisible, as the to see many more powerful drugs
safe for us to take. And because we UK governments All-Party Parliamen- that up to now, have only been available
think they are safe, we are much more tary Group on Drug Misuse is from the doctor and only with a
likely to take several OTC drugs in discovering. Dr Brian Iddon, the cross- prescriptionput on the shelves for
combination, even though they may party group chairman, said: Our everyone to buy.
well share some of the same active inquiry has only scratched the surface Thousands of prescription-only
agents, thereby increasing the amount of this problem. Yet, it isnt clear how drugs have already made the transition
of each agent we are taking every time. his enquiry can ever go deeper, as there to OTCa process known as Rx to
Indeed, the US Centers for Disease are no records of who is buying these OTC in the US and as OTC switching
Control and Prevention (CDC) has also drugs and how often, although one in the UKand many more are
reckoned that around half of all child- place that the enquiry could start is expected to follow suit as patents
ren under the age of three years are with a self-help group of 4000 people expire on a host of blockbuster
regularly given an OTC preparation, registered on a website because of prescription drugs. One example from
such as Tylenol or Calpol. their addiction to Solpadeine, an OTC last year was the switching of Novartis
Their potential dangers appear to concoction of codeine and parace- Prevacid 24HR, a heartburn remedy
become the subject of public concern tamol (BMJ, 2007; 334: 9178). and the first proton-pump inhibitor to
only when they affect a celebrity, such Very few people who are regularly obtain OTC approval in America since
as Hollywood film actor Heath Ledger, self-medicating realize that the drugs 2003. As a prescription drug, it was
who died in 2008 after overdosing on they are taking invariably contain among the top five best-sellers in the

2 WDDTY Dangerous drugs

US, with annual sales of $3.37bn in
Think twice about these OTC drugs 2008and yet, it has now become an
OTC remedy that is being marketed
Theyre household names and they may well be in your medicine cabinet right directly to the approximately 50
now. Yet, despite their popularity, you may want to think twice before you start million Americans who suffer from
popping any of these products. frequent heartburn (
u Advil or Motrin (ibuprofen): These are painkillers that can also reduce fever, article/idUSLE40551720090514).
but they can also cause stomach pain and dizziness. Their prolonged use As a result of this refocusing, the
can lead to ulcers, raised blood pressure, kidney and liver damage, and even OTC marketalready worth around
stroke and heart attack. $7.8bn in the US this year, and consis-
u Aleve (naproxen): A painkiller that also reduces inflammation, this can tently growing by 8 per cent annually
cause stomach pain, and its prolonged use can bring about the same since the early 1990sis set to double
adverse effects as Advil (see above). by 2023, according to the World OTC
u Aspirin (acetylsalicylic acid): One of the first non-steroidal anti- Pharmaceutical Market Analysis &
inflammatory drug (NSAID) painkillers, its preeminent position has been Forecasts, 20082023 (
challenged by newer, and supposedly safer, agents such as ibuprofen and publications/otc/world_otc_pharmaceutical_
paracetamol (acetaminophen in the US). However, it is still considered a first- market_analysis_forecasts_20082023.html).
choice remedy for migraine and as a preventative for heart disease. Yet, it Although the prescription drugs
causes gastrointestinal bleeding, Reyes syndrome in children and can be a market is far more lucrative, the
major cause of stroke in the elderly (see box, page 4). pharmaceutical industry is being
u Benadryl, Tylenol (diphenhydramine): These drugs are primarily intended forced to change its strategy. The
to ease gastrointestinal problems, although older patients also use them industry is reaching a significant
as sleep aids. They are increasingly being linked with cognitive impairment, watershed as scores of big-selling
causing confusion, agitation, memory loss and incoherent speech. proprietary drugs are soon to lose their
u Contac (pseudoephedrine): This decongestant causes dizziness, patents, which would allow a wash of
nervousness and sleeping problems. It should be avoided if you have high cheaper me-too generic drugs from
blood pressure, diabetes, prostate problems, thyroid disease or a heart competitors onto the market. To
condition. counter such an event, a drug company
u Nurofen (codeine, methylmorphine): This painkiller contains codeine, a often adopts a double-pincer move by,
controlled substance that can become addictive in chronic users. Codeine is on the one hand, supercharging the
found in many OTC remedies and, depending on the formula, can cause prescription drugsuch as by
nausea, euphoria and rash. Codeine is an opiod, a family of agents that can increasing its potency or making a
lead to fatal respiratory depression. Codeine metabolizes into morphine, and minor change to the formulation
this can be passed through a mothers breast milk in lethal amounts. which would then allow it to extend
u Nytol (diphenhydramine): This is a sleep aid and, like most OTC remedies its protective patent while, on the
for insomnia, its an antihistamine, which promotes drowsiness. Common other hand, making the original drug
side-effects, which especially affect older patients, include dizziness and available in the OTC marketplace.
forgetfulness, constipation and blurred vision. However, these remedies can The types of drugs that are expected
be fatal if you become a chronic user and you regularly overdose, as to make the switch include gastro-
happened to Hollywood film actor Heath Ledger. Overdosing is common intestinal remedies, cholesterol-
as the body becomes adjusted to the recommended dose. lowering agents, osteoporosis treat-
u Solpadeine (paracetamol, codeine): This is one of the most popular OTC ments and contraceptives. Also, the
painkillers in the UK. Although it is supposed to be taken for no more than pharmaceutical industry is fiercely
three days, many people become addicted to it. The combination can cause lobbying drugs regulators such as the
drowsiness, and serious liver and kidney damage, especially if taken US Food and Drug Administration
together with another OTC remedy that contains paracetamol. Other side- (FDA) to extend the categories of
effects include constipation, rash and nausea. agents that can be sold as OTC. Its a
u Sudafed (phenylephrine): See Contac (above). battle theyre expecting to win, and
u Tylenol (acetaminophen): This was promoted as a safer alternative to new categories are likely to be
aspirin, but it can cause kidney failure, and several prescription drugs that included in the OTC arena, says
contain this agent are now being closely monitored. Tylenol also contains industry analyst group Kalorama
codeine, a controlled substance in most countries. Its reckoned that (
acetaminophen is responsible for 100 deaths and 56,000 emergency-ward recession-could-pump-mkt-over-counter-
visits every year in the US alone. drugs/2009-04-20).
u Vicks, Robitussin (dextromethorphan): These cough-and-cold remedies However, the battle is already all
contain DXM, a chemical that is similar to morphine; indeed, some teenagers but over in the UK, which is known to
deliberately overdose on them to get a high. The US Drug Enforcement operate one of the most liberal drug-
Administration (DEA) has classified DXM as a drug of concern, but has licensing regimes in the world, where
done nothing to restrict its sales in stores. cholesterol-lowering statin drugs were
allowed to be sold without a pres-
cription as early as 2004.

WDDTY Dangerous drugs 3

Over-the-counter drugs

Whos at risk?
As with most drugs, the young, the elderly and those who are OTC appetite suppressant was found to increase stroke risk
pregnant are most at risk from the side-effects of by more than 16 times, while women who had taken an OTC
OTC remedies, although any userespecially any chronic cough or cold remedy that contained phenylpropanolamine
usercan suffer an adverse reaction. were more than three times more likely to suffer a stroke (N
Around 71,000 preteenagers are rushed to an emergency Engl J Med, 2000; 343: 182632).
ward in the US every year after being poisoned by an OTC Nursing mothers should also avoid any OTC remedy that
drug, such as cough syrup (Am J Prev Med, 2009; 37: 1817), while contains codeine. As this agent metabolizes into morphine, it
many teenagers are deliberately overdosing with DXM, which can pass from the breast milk to the babyat levels that can
is found in cough medicines, to experience a high. From be fatal to the infant.
1999 to 2004, there was a 15-fold increase in cases of DXM However, the elderly are perhaps at the greatest risk of
poisoning and over-doses among young Americans aged suffering an adverse reaction to an OTC drug, partly because
nine to 17 years (Arch Pediatr Adolesc Med, 2006; 160: 121722). they are generally taking more of them and their immune
The under-12s who take aspirin are also at greater risk of systems are less able to cope, but also because it is usually
developing Reyes syndrome, a rare and often fatal multiorgan part of a drugs cocktail that includes prescription medications,
disorder (BMJ, 2002; 325: 988). Yet, ironically, acetaminophen is too. Also, aspirin is often part of the health regimen in the
promoted as safe for children. However, the drugs regulators elderly, who take it is a preventative against heart disease and
are now beginning to realize that its even more dangerous stroke.
than aspirin, and can cause life-threatening liver problems But a study from Oxford University suggests that the drug
(JAMA, 2009; 301: 23156). has a paradoxical effect among the over-75sand
Pregnant women who take an NSAID (non-steroidal anti- is, in fact, a cause of stroke resulting in either disability or
inflammatory drug) like aspirin increase their risk of death.
miscarriage by 80 per cent. The risk is even higher when the The researchers have discovered that aspirin had caused
drug is taken at around the time of conception or a sevenfold increase in stroke in the elderly patients who
for more than one week. These drugs are thought to suppress participated in their study. As research team leader Professor
the production of prostaglandins, fatty acids that help to Peter Rothwell said: There are elderly people who take
ensure that an embryo is successfully implanted in the womb aspirin as a lifestyle choice, and, in that situation, the trials
(BMJ, 2003; 327: 368). have shown theres no benefit. And what our study suggests
Women who take any drug that lowers their folic-acid is that, particularly in the very elderly, the risks of aspirin
levelsincluding OTC preparations such as NSAIDsrun a outweigh the benefits (Lancet Neurology, 2007; 6: 48793).
far greater risk of giving birth to a child with a birth defect. Also, In addition, OTC sleep aids are a significant cause of falls
the risk of cardiovascular defects increases in elderly people. Falls and complications after falls are the fifth
by 240 per cent and that of oral clefts, by 160 per cent most common cause of death in the developed world.
(N Engl J Med, 2000; 343: 160814). Researchers from the University of British Columbia in
OTC cough remedies that contain DXM are another cause Canada reviewed 22 studies, involving more than 79,000
of birth defects. One studyalbeit in animals, so it may not elderly participants who had falls, and found that prescription
apply to humansfound that DXM is so powerful that just one and OTC sedatives and anti-depressants were mainly
dose can result in a birth defect, and can affect the embryo responsible for the accidents (Arch Intern Med, 2009; 169:
even before the pregnancy is known. So, all women who are 195260).
pregnant, or who are planning to become so, are advised not However, both the elderly and the young are at special risk
to take any OTC cough medicine that contains DXM (Pediatr from OTC sleep aids that contain antihistaminesand
Res, 1998; 43: 17). diphenhydramine in particular. While the drugs can cause
Women in general who use an OTC slimming aid that abnormal muscle spasms and blurred vision in the general
contains phenylpropanolamine will dramatically increase their population, they also cause nervousness and, paradoxically,
risk of stroke. In one study of 702 women who had suffered a insomnia in the very young and in older adults
stroke and who were compared with 1376 healthy controls, an (Pharmacotherapy, 1994; 12: 4926).

The British drugs regulators were worldwide ( therapeutic areas for OTC switching.
undeterred by the dubious safety 1481178.stm; This explosion in OTC sales is also
record of statins, which lists heart s/2916979.stm). fuelled by consumer demand. More
failure, liver and kidney damage, and a As a spokesman for the pharma- and more people are looking to self-
potentially fatal muscle-wasting dis- ceutical market research company medicate, which they consider to be
order known as rhabdomyolysis Piribo states: The worldwide OTC inexpensive, convenient and safe,
among their side-effects. In 2001, one market will see a remarkable period of compared with a visit to the doctor,
statin, Baycol, was withdrawn from the dynamic change. Ageing populations which might involve a more careful
market after 31 people died because and rising incidence of lifestyle review of the problem. Consumer
of rhabdomyolysis in the US and after diseases, as well as the need to reduce demand for the heartburn remedy
being linked to around 100 deaths healthcare costs, will open up new Prilosec became so great in 2004 that

4 WDDTY Dangerous drugs

pharmacies were out of stock for most
of the year. Although manufacturer The history of OTC drugs
Proctor & Gamble increased its
production, it wasnt until 2005 that Regulators on both sides of the Atlantic have been slow to regulate OTC
shelves were replenished (Berenson A. drugs, as well as the active agents they contain. In the US, alcohol, cocaine,
Where Has All the Prilosec Gone? The New York
marijuana and opium were regularly included in therapeutic concoctions
Times, March 3, 2005).
without the need for any special licence, and that only changed with the
To make the switch from pres- passing of the US Federal Food, Drug, and Cosmetic Act (FFDCA) of 1938.
cription to OTC, the drug manufac- Yet, even then, this piece of legislation failed to distinguish between
turer will often reduce the dose level drugs that were available only by prescription and those that were sold in
or change the formulation to produce stores. The situation was clarified only slightly in 1951 with an amendment
a weakened version for the mass to the act that defined prescription drugs as those that were habit-forming,
market. Nevertheless, these smaller toxic, unsafe or used only under a doctors supervision. In other words, a
dosages can still be lethal, and is drug could be sold over the counter if it was none of the above although,
certainly addictive, as the few statistics even today, many OTC drugs are, in fact, habit-forming and toxic, and
that are available demonstrate. possibly unsafe.
Indeed, our drugs watchdogs are at The laws only began to tighten up in 1962 with the thalidomide scandal
pains to point out that there is no such in the UK and yet another amendment to the FFDCA of 1938 in the US. The
thing as a safe drug, and they urge latter then required that OTC drugs should be both effective and safe, an
consumers to read the label before amendment that has been little more than window dressing, as no reporting
taking any medication. But as OTC system was created to confirm either of these qualifiers.
regulations are far less rigorous than In the UK, the College of General Practitioners set up a Register of
they are for prescription remedies, the Unexpected Toxicity in the wake of the thalidomide scandal, which caused
demands and guidelines for the 5000 appalling deformities in newborn babies in the UK, and around 10,000
manufacturer regarding the inclusion cases worldwide. One year later, the British did what the British do best:
of patients information are hardly they set up a committee which, in 1963, suggested that the problem of
onerous. For example, the safety sheet drugs monitoring and regulating could best be served by the creation of a
that comes with the prescription-only new committeethe Committee on Safety of Drugs (CSD)which, in turn,
version of Motrin, a painkiller that comprised four subcommittees.
contains ibuprofen, includes possible However, despite all these committees, the OTC market was still not
side-effects such as oedema, blurred covered and was not regulated until 1971, when the Medicines
vision, nausea, heartburn, diarrhoea, Commissionthe main statutory advisory body set up under the UK
gastric ulcer with bleeding and/or Medicines Act of 1968began its work to monitor all drugs.
perforation, dizziness, nervousness,
rash and tinnitus. In contrast, the label
on the OTC version of Motrin merely The committee argued that the non-autistic controls, the children who
mentions that ibuprofen may cause chances of overdose and severe liver were given an aceta-minophen-
stomach bleeding, and the list of side- injury were high, and that the risks far containing remedy were six times more
effects has been omitted. outweighed any benefits that such likely to develop autism after the
drugswhich include Vicodin and vaccine, and nearly four times more
Hidden interactions Percocetoffered. likely to suffer regression in
The OTC drug manufacturer also Also, the report stated that aceta- their development, compared with the
doesnt have to make any mention of minophen, which is commonly used to controls. The children who had been
the fact that the remedy can interact reduce fever, had been linked to 56,000 given ibuprofen to treat fever after the
with other drugs or remedies, emergency room visits, 26,000 hos- MMR vaccine had no autism (Autism,
including vitamins. Paracetamol pitalizations and 458 deaths during 2009; 13: 1234).
(acetaminophen) is a common pain- the 1990s in the US. Yet, no one Most cough medicines include
killing agent found in hundreds of recommended that any OTC drug dextromethorphan (DXM) and, yet, the
OTC remedies and, yet, none of them containing acetaminophen be taken off warningif there is one at allis
mentions that it can increase bleeding, the market (http:// woefully inadequate. Although one
possibly to a dangerous level, if taken 2009/06/30/fda-panel-urges-ban-vicodin- OTC preparation, Robitussin, men-
in conjunction with the blood-thinning percocet/). tions that it shouldnt be taken with
drug Coumadin (warfarin). Acetaminophen is even suspected any prescription antidepressant known
The FDA is also becoming increas- of being a cause of autism. Its found in as an MAOI (monoamine-oxidase
ingly concerned about prescription the childrens OTC remedy Calpol, inhibitor), it doesnt state that the
drugs that contain acetaminophen, which is regularly used by parents to interaction is, in fact, life-threatening.
and one of their advisory committees reduce fever, which also commonly DXM also interacts with other anti-
last year went so far as to recommend occurs after receiving the MMR depressants such as Prozac, Paxil and
that all drugs that combined this agent (measlesmumpsrubella) vac-cine. In Zoloft (all of which are SSRIs, or
with narcotics should be immediately one study of 83 children with autism selective serotonin-reuptake inhibi-
removed from the market. who were compared with 80 healthy, tors), to produce a serious condition

WDDTY Dangerous drugs 5

Over-the-counter drugs
known as serotonin syndrome, which Association (GPhA) recognizes the controls prescription drugs. While it
can trigger symptoms such as muscle double standards that now apply to is forgivable that the consumer might
twitches, fever, nausea, dizziness, prescription and OTC drugs, and is believe OTC drugs are safer, its not
confusion, shock and coma. DXM side- calling for the same approval acceptable that our drugs regulators
effects, even when not mixed with process for all drugs, irrespective of should also share the same view.
another drug, include impaired the way in which they reach the In fact, the regulators know that
judgement, loss of coordination, marketplace and consumers. OTC drugs are every bit as dangerous
dizziness, nausea, hot flashes, hallucin- While FDA-approved prescrip- as their prescription counterparts,
ations, brain damage, seizure and tion drugs are subjected to a rigid even though they may be acting
death. Again, virtually no OTC drug application-based approval process otherwise. Why else do OTC drugs
that contains DXM mentions these . . . other products are marketed not have to list all of their possible
possible adverse effects. either under a minimally regulated adverse effects, or any of their
Drug manufacturer Merck, which system or no regulatory system at possible interactions with other drugs
also publishes The Merck Manual of all. Specifically, numerous OTC and medications.
Medical Information, says: Often, the drugs have been on the market for But worse than that is the fact
labels of OTC drugs do not list the full years and some predate the laws that the OTC market is completely
range of possible side effects. As a that require proof of safety and invisible. Nobody knows who is buying
result, many people assume that these effectiveness before marketing . . . these drugs or what happens to them
drugs have few, if any, side effects. For [so] the unregulated OTC drug afterwards. This is because theres
example, the package insert for one market continues to fall between little incentiveand almost no
analgesic (not named) cautions people the cracks, an association fundingto investigate the dangers
not to take the drug for more than spokesman says ( of OTC drugs. However, the little that
10 days for pain. However, the possible media/press-releases/2009/02/12/fda- has been done uncovers a worrying
serious side effects that can occur with standards-and-foreign-inspections). picture, with aspirin alone causing
long-term use (such as life-threatening around 100,000 deaths worldwide
bleeding from the digestive tract) are Double blind every year.
not mentionednot on the box, With the OTC market becoming the The OTC market is truly
bottle, or package insert (www.merck. new focus of Big Pharma, it is medicines dark side, but its time
com/mmhe/print/sec02/ch018/ch018a.html). imperative that it is protected by the that light be shed upon it.
Americas Generic Pharmaceutical same regulatory framework that Bryan Hubbard

6 WDDTY Dangerous drugs

Death by aspirin
Aspirin may be a major killer, and one that none of us even suspects
spirin is the ultimate lifestyle may soon overtake hypertension (high

A drug, and is seen as one of

our great allies in warding off
heart disease. With the
encouragement of health guardians
around the world, we pop 100 billion
blood pressure) as the major cause of

What studies now tell us

In the first of the new studies,
pills of this just-in-case drug every researchers reckoned that the drug is
year, and 37 per cent of them are taken killing 20,000 Americansand
by healthy people as part of their daily sending another 100,000 to hospital
health regime. every year just because
Its the inexpensive and readily of GI problems. Astonishingly, each of
available magic bullet that can protect these deaths and reactions is slipping
us against cardiovascular disease, under the radar, and is not being
mankinds greatest killer. The humble associated with aspirin at all.
aspirin can, according to its
proponents, reduce blood pressure and
help thin the blood, so lowering the The story of aspirin
risk of stroke and heart attacktwo
functions that today dwarf its original
Aspirin holds an unusual place in trademark law. As Aspirin with a
purpose as a painkiller, an anti-
capital A, it is a protected brand, owned by Bayer, the German
inflammatory and antipyretic (fever-
pharmaceutical giant.
As aspirin, it is a generic drug that can be used in countries where
Best of all, it appears to be a
Aspirin is not trademark-protected. Around 50 other over-the-counter
relatively benign drug. The American
preparations contain aspirin, using either the name or ASA, an
Association of Poison Control Centers
abbreviation that stands for Aspirins generic name, acetylsalicylic acid.
receives reports of just 59 aspirin
Aspirin was the very first drug in the family of NSAIDs (non-steroidal,
deaths in the US each year, while
anti-inflammatory drugs) when Bayer began marketing it in 1899, along
researchers put the mortal-
with another of the companys discoveries, heroin. Its principal
ity rate for all painkilling, non-
ingredient is salicylic acid, derived from the bark of the willow tree and
steroidal, anti-inflammatory drugs
from the herb meadowsweet. It was recognized by Hippocrates as a
(NSAIDs) such as aspirin, ibuprofen
pain-reliever and an antipyretic (fever-reducer) as long ago as in the 5th
and naproxen at around 7600 deaths a
century BC .
year (Scand J Rheum Suppl, 1992; 92: 214).
Chemists at Bayer were successful in synthesizing salicylic acid with
Either way, doctors argue that these
the common chemical acetic anhydride, so giving Aspirin its generic
figures represent an entirely
acceptable risk compared with the
Despite its widespread use and popularity, no one understood how
many thousands more who might
the drug worked until 1971, when the British pharmacologist John Vane
otherwise have died because of heart
found that aspirin suppresses the production of prostaglandins and
thromboxanes, hormones that regulate many physiological functions.
But scientists are now discovering
Today, we globally consume around 35,000 tons of aspirin every
that we have all been dramatically
yearamounting to around 100 billion tabletsa figure that is increasing
and catastrophically misled by the
annually by 15 per cent. Aspirin continues to be viewed as a benign
assurances of the medical community.
painkiller, which has helped to fuel its growing use at
Far from being benign, aspirin may be
a time when bad news and scares have hounded some of the other
a major killer in our society, and one
NSAIDs and COX-2 drugs.
that is never suspected.
Most recently, the COX-2 painkiller Vioxx was withdrawn from the
The new claim centres on the drugs
market after it was found to cause heart problemssome fatal. It was the
well-documented side-effect of causing
subject of the largest civil lawsuit in history until its manufacturer Merck
seriousand, in some cases, fatal
settled with a $4.85bn payout.
gastrointestinal (GI) bleeding. But
Aspirin has been dogged by its own fair share of side-effects. The most
researchers in a separate study have
common are stomach bleeding and other GI problems, but added to that
discovered a new, and worrying, side-
are stroke, anaemia, ulcers, liver damage, hives, wheezing, tinnitus,
effect of aspirinit may be a major
chronic catarrh, headache, confusion and hypotension (low blood
cause of stroke among the elderly.
pressure) followed by collapse. Asthmatics have also died from a severe
Because of its widespread use,
attack after having taken aspirin.
researchers warn that these little pills

WDDTY Dangerous drugs 7

Over-the-counter drugs

Researchers at the Eastern Virginia

Medical School made their alarming Is it truly a heart helper?
discovery when they interviewed
patients at a clinic that specializes in Aspirins popularity today is more to do with its ability to protect us from
GI problems. They found that one in cardiovascular disease (CVD) than as a painkiller, for which it has been
five patients was taking aspirin or some superseded by newer kids on the block such as ibuprofen.
other painkilling NSAID, but the fact Around 37 per cent of the 100 billion aspirin pills swallowed every year are
wasnt being reported to the medical taken as a preventative against heart disease and stroke, while 23 per cent of
staff because it wasnt regarded as users are arthritis sufferers who take it for its anti-inflammatory qualities. Only 14
significant. per cent of users take it to relieve
This reflects a common mis- a headache.
perception that these medications are Its principal role as an anti-inflammatory and antipyretic began to change
insignificant or benign when actually when Dr L.L. Craven, a GP working in California, discovered that it was providing
their chronic use, particularly among benefit to his heart patients (Mississippi Valley Med J, 1953; 75: 3844).
the elderly and those with conditions More recent trials have confirmed its role as a preventative agent, and
such as arthritis, is linked to serious particularly for heart patients. In 1998, the US drugs regulator, the Food and Drug
and potentially fatal GI injury and Administration (FDA), widened the scope of aspirin to encompass its
bleeding, said Dr David Johnson, one new role, especially among those who had had a heart attack, stroke, angina, or
of the Virginia researchers. bypass surgery or angioplasty.
If the researchers death and injury Since then, two meta-analyses have concluded that aspirin can reduce the
rates for the US is correct, this could risk of cardiovascular disease by 13 per cent (Arch Intern Med, 2000; 160: 31237),
mean that the worldwide aspirin and and heart attack by as much as 32 per cent (Heart, 2001; 85: 26571).
other NSAID death toll is 100,000 Despite these glowing recommendations, however, many groups remain
individuals every year. Whats more, a cautious and recommend that healthy people not use aspirin as a prophylactic
further 500,000 of us will need hospital just-in-case. The US Preventive Service Task Force is still not convinced and,
care to treat a serious reaction to the despite the meta-analyses, says the data are insufficient to make any categorical
drug, such as the result of a GI reaction pronouncement (Ann Intern Med, 2002; 136: 15760). The European Society of
(Proceedings of the Annual Scientific Meeting of Cardiology suggests that those at high risk of heart disease should take aspirin
the American College of Gastroenterology, 15 only at a low daily dose of 75 mg.
October 2007).Currently, none of these Similar cautious voices have been raised concerning aspirins ability to
deaths is even recorded as an aspirin prevent stroke, despite the seemingly impressive research. The Antiplatelet
fatality. Trialists Collaboration (ATC) prepared a series of landmark trials that appeared
Equally worrying is the drugs effect to establish aspirin as an important agent for treating stroke.
among the over-75s. Far from Yet, within a year, its findings were being questioned. The Thrombosis
protecting them against stroke, it Research Institute analyzed the third arm of the ATC trial, which focused on the
appears to be causing just such an efficacy of aspirin in reducing venous thrombosis and pulmonary embolism after
attack that is either fatal or results in surgery. The Institute declared that some of the ATCs conclusions were not
disability. Researchers at Oxford justified, and that several of the studies included in the meta-analyses werent of
University have discovered that a high-enough standard (BMJ, 1994; 308: 12137).
the drug has caused a sevenfold Worse, the ATC researchers had also played down the issue of side-effects
increase in intracerebral haemor- such as internal bleeding. Without them, said the Institute, the true riskbenefit
rhagic strokebleeding within the ratios couldnt be worked out.
brainduring the past 25 years among In the face of these criticisms, the ATC researchers moved away from their
groups of elderly patients who earlier effusive position and instead suggested that aspirin was not the complete
participated in their trial. solution, but should be seen as part of a range of measures.
Research-team leader Professor The ATC studies were an interesting object lesson in how the myth of the
Peter Rothwell says that aspirin may healing powers of aspirin always manages to outpace the actual studies on
soon replace high blood pressure as the which it has been founded. Nevertheless, despite the legend, there is only a
leading cause of intracerebral handful of research to support the theory that aspirin can prevent heart disease
haemorrhagic stroke, especially among and stroke. Even used as a preventative by heart patients, the evidence is thin on
the over-75s. the ground.
There are elderly people who take The editorial team of a prestigious peer-reviewed journal once stated that
aspirin as a lifestyle choice, he says, aspirin seems as effective as any other single agent or combination of agents
and, in that situation, the trials have (BMJ, 1994; 308: 712), which is saying far less than aspirins advocates believe
shown theres no benefit. And what our
study suggests is that, particularly in
the very elderly, the risks of aspirin out- between 2002 and 2006. While the same, mainly because there had been
weigh the benefits. overall rate of stroke caused by high an increase in the number of strokes
In Rothwells study, researchers blood pressure had dropped by 65 per among patients taking blood-thinners
assessed the records of stroke victims cent between those two periods, the such as aspirin.
between 1981 and 1985, and again rate among the over-75s remained the The team discovered that the

8 WDDTY Dangerous drugs

use of these drugs had increased examined patients records from coated, which allows the tablet to
dramatically and especially among databases in the UK and Spain found transit through the stomach to the
healthy people who were taking that 60 per cent of those small intestine before releasing the
the drugs as a preventative. From 1981 who suffered a GI reaction from an medicine, or buffered, where the
to 1985, only 4 per cent of patients NSAID were aged over 60, 13 per cent standard pill is coated with a sub-
were taking a blood-thinner, but this were using several NSAIDs in stance that neutralizes stomach acid.
had risen to 40 per cent between 2002 combination, and 6 per cent had a But again, far from reducing the GI
and 2006 (Lancet Neurology, 2007; 6: recent history of peptic ulcers, even risk, these coatings appear to increase
48793). though patients with pre-existing GI it. Researchers from the Boston
In fact, the true dangers of aspirin problems should not be taking any sort University School of Medicine
have been known for some time, of NSAID in the first place (BMC interviewed 550 hospital patients who
although no one has been prepared to Medicine, 2006; 4: 22). had major upper gastrointestinal
do anything about it. Scientists from But perhaps the most lethal drug bleeding about their aspirin use. To
the West Midlands Regional Health combination is an NSAID with their surprise, they found that those
Authority in Birmingham were among an SSRI (selective serotonin reuptake who had regularly taken buffered
the first to raise the warning flag 12 inhibitor) type of antidepressant such aspirin were at a slightly greater risk of
years ago, when they did an as Prozac, Zoloft or Paxil. In fact, this is developing GI problems than were
investigation into the reasons why a common drug cocktail, especially those taking regular aspirin tablets. At
people were in hospital for treatment among arthritis sufferers, who are doses greater than 325 mg, patients
of bleeding peptic ulcer. often given an NSAID to ease their joint taking the buffered tablets were seven
At that time, they discovered that pain and inflammation, and an SSRI to times more likely to develop GI
12.8 per cent of the 1121 patients ease their mild depression. problems whereas the risk was
being investigated were regular users When these two drugs are taken increased nearly sixfold with the
of aspirin, which they defined as five concomitantly, the risk of upper standard pills (Lancet, 1996; 348: 14136).
days a week for at least a month. When GI haemorrhage increases by 6.3
they compared these patients against times. Translated into everyday usage, Aspirin: still a wonder drug?
other patients with the same prob-lem, a patient has to take the combination Extraordinarily, the popular use of
but who were not regularly taking just 82 times before suffering a serious aspirin seems to be immune to
aspirin, it was evident that taking the gastrointestinal adverse reaction. Such any bad news. This may be because
NSAID had increased the risk of an event would occur less than three aspirin is still perceived as being a
hospitalization for bleeding peptic months into the treatment, assuming wonder drug. Every year, its
ulcer by 2.3 times at a low dose of just the combination is taken daily. estimated that around 3500 studies
75 mg, and by up to 3.9 times at the Researchers from the University of are carried out on the drug, and
more standard dose of 300 mg (BMJ, East Anglia made this discovery when researchers seem to consistently come
1995; 310: 82730). The 300-mg dose is they carried out a meta-analysis of four up with new health problems that they
the recommended level for just-in-case, trials involving a total of 153,000 believe it can solve. Its been claimed to
or prophylactic, use against heart patients who were taking either an fight cataracts (Arch Ophthalmol, 1992; 110:
disease. SSRI or an NSAID, or a combination of 33942), and cancers of the prostate,
These researchers didnt track the the two types of drug. Patients who colon, pancreas, upper GI tract, and
progress of patients after identifying took just the SSRI increased their risk lungclaims that usually no one
their cause of hospitalization, but one of a GI reaction 2.4 times, and those is able to replicate and so are,
group of scientists didand came up taking just an NSAID had a 3.2-times eventually, forgotten.
with a horrifying picture. Of those who greater risk (Aliment Pharmacol Ther, 5 This is, of course, in addition to its
were being treated in hospital for October 2007; doi: 10.1111/j.1365- more traditional, and accepted, uses as
serious upper gastrointestinal bleeding 2036.2007.03541). an antipyretic to reduce fever in cases
or perforation, 10 per cent had died. Lead researcher Dr Yoon K. Loke of rheumatic fever, as an anti-
commented: Before I did this study, I inflammatory in cases of rheumatoid
Who are most at risk? didnt worry at all when I saw patients arthritis and osteoarthritis, and as a
This alarming scenario was derived who were on combinations of SSRIs painkiller for minor aches and pains
from an analysis of 12 studies and NSAIDs. Now that I have seen the such as headache.
published between 1980 and 2000. fairly substantial excess risk, physicians But if the risks of regularly taking
Those who were especially at risk were should review the patients chartsdo aspirin outweigh its benefits among
older individuals, and there were they need to be on these drugs at all, or healthy over-75s, as suggested by
around twice as many men as women are there safer alternatives? Oxfords Professor Rothwell, then
who ended up in hospital Gastrointestinal problems with should healthy individuals of any age be
(J Clin Epidemiol, 2002; 55: 105763). aspirin have been known for a long taking it?
So, as well as age and gender, people timeeven if the actual severity and Not according to Charles H.
who take several NSAIDs in extent have only recently been Hennekens, former chief of preventive
combination also increase their risk of revealedand manufacturers have medicine at Brigham and Womens
having a serious GI reaction. In a tried to reduce the risks by either Hospital in Boston, and one of aspirins
separate study, researchers who producing a version that is enteric- main advocates. Yet, even he believes it

WDDTY Dangerous drugs 9

Over-the-counter drugs

is wrong for any healthy individual to patient taken a daily aspirin. It points
take aspirin as a preventative as the to research that suggests that aspirin
risks are simply too high. can help to prolong the lives of people
A 30-year-old womans risk of a who have suffered a stroke or heart
heart attack is typically very small, and attack, or recurring blockages
remains so even over the next 30 years. following heart bypass surgery or
Aspirin would give her no benefit and it angioplasty to clear obstructed
could cause gastro-intestinal effects or arteries.
dangerous bleeding, he says in a Food But these positive claims have to be
and Drug Administration (FDA) report. countered with the more recent
Children aged under 12 should also findings that the drug could be killing
no longer be given aspirin because of 20,000 Americans every year because
the very real danger of Reyes of GI complications alone, a figure that
syndrome, a rare, often fatal, disorder may well increase if stroke victims are
primarily seen in children recovering also included.
from a viral illness and associated with But no drug is a substitute for
aspirin use (BMJ, 2002; 325: 988). a sensible lifestyle. A healthy diet that
If the healthy should not be taking is rich in vegetables and fruit,
aspirin, this suggests that nearly 40 per moderate exercise, and stress- and
cent of daily aspirin use is cigarette-free living can do more for He says: If you are healthy and have a
inappropriate, and may even be the healthy individual and the low risk of heart disease or stroke, the
endangering thousands of lives without recovering patient alike. increased risk from side-effects of
any realistic benefits. As the FDAs Debra Bowen says: aspirin are likely to outweigh the
Nevertheless, it should be part Physicians really need to look at benefits of preventing stroke.
of the daily health regime of anyone aspirin in the context of complete care, Aspirin is as close as medicine has
who has a heart problem, says the as part of a whole treatment plan for ever come to producing a magic
American Heart Foundation. It people at risk of heart attack or bulletand one that appears to be
estimates that between 5000 to 10,000 stroke. Teflon-coated, too. Neverthe-less, given
of the 900,000 lives lost each year to Its a view shared by Dr Peter these latest discoveries, its an ideal
cardiovascular disease in the US alone Coleman, deputy director of res-earch that is apparently as far away as ever.
could have been prevented had the for the Stroke Association in the UK. Bryan Hubbard

10 WDDTY Dangerous drugs

Drugs for depression

The great depression myth

SSRI drugs sell on the basis of the false chemical imbalance theory
very year around the world,

E we take $13bn (6.6bn)-

worth of antidepressants,
and more than 80 per cent
of those is an SSRI (serotonin
selective reuptake inhibitors) such as
Prozac, Paxil and Zoloft.
SSRIs are among the best-selling
drugs in medicine, and their enor-
mous success is based on the
chemical imbalance theory, which
proposes that people are depressed
because they are low in serotonin, a
brain chemical and neurotransmitter
that acts on the nervous system.
An SSRI redresses such a chemical
imbalance by helping to promote
serotonin, and can treat not only
depression, the manufacturers claim,
but also other psychiatric problems
such as social anxiety disorder and
obsessivecompulsive disorder. as well as the general publicthat
The SSRI signalled a revolution in severe depression is the result of a psychiatry, 1996; 29: 211). Similarly,
mental care. Suddenly, clinical and chemical imbalance nd, especially, depressed people who were given
severe depression wasnt something low levels of the neurotransmitter huge increases of serotonin failed to
that the sufferer just had to endure serotonin in particular. Joseph witness any improvements in their
or learn to get over. Instead, heres a Schildkraut was one of the pioneers condition (Arch Gen Psychiatry, 1975; 32:
simple remedy to hand: a chemical of the general theory that chemical 2230).
to treat a chemical. As a result, weve imbalances cause depression and, in Not only has neuroscience been
become a Prozac Nation, as Eliza- 1965, he postulated that depression unable to prove the theory in
beth Wurtzels best-selling book says. was associated with low levels of a independent studies, it has found
The pharmaceutical industry has neurotransmitter. These imbalances plenty of evidence to suggest that
been the major promoter of the caused mood swings, and the prob- depression and other mental
depressionserotonin theoryfor lem could be corrected by drugs, he disorders are the result of far more
obvious reasons. Yet, astonishingly, believed. Two years later, researchers complex factors than a simple
the concept has never been actually zoned in on serotonin as the neuro- neurotransmitter deficiency.
proven since it was first postulated in transmitter responsible (Br J Psychiatry, The lack of substantiating evi-
1967and not because there havent 1967; 13: 123764). dence isnt helped by the fact that
been many attempts to do so. But this acceptance has far more no one knows what an ideal serotonin
Given that the theory remains to do with aggressive marketing by level is supposed to look like, let
unproven, its not surprising that the the drug companies, who sell their alone the profile of a pathological
SSRI antidepressant is far less SSRIs on the basis of the theory, than imbalance.
effective than the drug companies research from neuroscientists, who There is not a single peer-
are claiming. In a meta-analysis of have triedunsuccessfullyfor 40 reviewed article that can be
both published and unpublished years to come up with conclusive evi- accurately cited to directly support
trials so far, researchers found that dence to support the theory. claims of serotonin deficiency in any
the trials, usually funded by the drug Researchers who analyzed the mental disorder, says Jeffrey
manufacturer itself, either put an cerebrospinal fluid of clinically Lacasse, a PhD candidate from
unwarranted positive spin on the depressed and suicidal patients Florida State University and co-
results or were suppressed if the couldnt find any differences in their author (with neuroanatomy professor
results were not positive (N Engl J Med, serotonin levels compared with Dr Jonathan Leo of Lake Erie College
2008; 358: 25260). healthy controls. Even participants of Osteopathic Medicine) of the essay
in medical trials whose levels of Serotonin and Depression: A
Whats the idea? serotonin were deliberately lowered Disconnect Between the Advertise-
Its generally accepted by doctors failed to become depressed (Pharmaco- ments and the Scientific Literature

WDDTY Dangerous drugs 11

Drugs for depression

(PLoS Med, 2005; 12: 12116).

The psychiatric bible, The Diag- What can cause depression?
nostic and Statistical Manual of
Mental Disorders (DSM-IV; published Depression is a chronic and debilitating condition that goes far beyond feeling
by the American Psychiatric Associa- down or having the blues. While doctors recognize that it can take various
tion), lists the definitions of all psy- formssuch as moderate or severe, or clinicalthey dont know precisely
chiatric diagnoses, and does not list why some people become depressed, other than accepting that it can be
serotonin as a cause of any mental due to a complex mix of causes. However, the one thing that is known with
disorder. However, the Textbook of certainty is that the oft-repeated theory of a chemical imbalance is simplistic and
Clinical Psychiatry, 4th edn (Hales not supported by any scientific evidence.
RE, Yudofsky SC, eds. Washington, While patients help groups often point to obvious causes of depression such
DC: American Psychiatric Publish- as death in the family, job loss or chronic illness, WDDTYs scouring through the
ing, 2003) does describe serotonin literature has uncovered many other, often unsuspected, causes.
deficiency as an unconfirmed u Hypothyroidism. Around one in five cases of chronic depression are
hypothesis, adding: Additional believed to be due to the body producing too little thyroid hormone. One
experience has not confirmed the study found that women with even just mildly decreased thyroid function had
monoamine depletion hypothesis. three times the rate of depression compared with the average (Ann Rev Med,
1995; 30: 3746). To check if your thyroid gland is underperforming, place a
The SSRI explosion thermometer under your armpit for 10 minutes immediately upon waking in
Nevertheless, and despite the lack of the morning. Any temperature below the normal range of 97.898.2 degrees
evidence, SSRI drug sales increased F (36.637 degrees C) may be indicative of an underactive thyroid.
by 353 per cent between 1981 and u Low blood sugar. This conditionwhich has the medical name of reactive
2000 (Ann Pharmacother, 2002; 36: 1375 hypoglycaemiais a recognized cause of depression. It can occur after
9). Indeed, its even anticipated that compulsive snacking on sweet or starchy foods and, once these foods and
SSRI sales will peak in 2010 with carbohydrates are removed from your diet, the depression may well lift.
global revenues of $14.6bn, and u Irritable bowel disease. Gastrointestinal problems are a major cause of
Japan is expected to be a major irritability and depression. One-third of all sufferers of Crohns disease
market for growth over the next complain of headache, eye problems and depression (South Med J, 1997; 90:
couple of years, with sales there 60610).
anticipated to increase by 52 per u Coeliac disease. Depression is associated with this gastrointestinal
cent (Datamonitor; at www.marketresearch. condition, where the inner lining of the small intestine is damaged by eating
com/search/results.asp?sid=92042647- wheat, rye, oats and barley.
406931770-490552493&query=ssri+future+ u Allergies. One study found that a third of all depressed people also suffer
use+Japan&vendorid=72&publisher=Datam from some sort of allergy such as to certain foods, or hayfever or bronchial
onitor&cmdSubmitLt=Go). asthma (J Affect Disord, 1981; 3: 2916).
The first blockbuster SSRI, Prozac
(fluoxetine hydrochloride), was
launched in 1986, and is the most Pfizers TV advertising for Zoloft has since 1997. In fact, the Irish Medical
widely prescribed antidepressant claimed that depression may be due Board has banned GlaxoSmithKline
medication in history, according to to a chemical imbalance, and that from claiming in its patient
its manufacturer, Eli Lilly. Another Zoloft works to correct this information that Paxil corrects a
SSRI, Pfizers Zoloft (sertraline), was imbalance. In the support literature chemical imbalance. Nevertheless,
the 10th best-selling drug in the for its SSRI, Pfizer states that the company continues to make the
world in 2003, with sales of $3.4bn. scientists believe that it (depress- claim on its website and in other
Before the SSRIs were developed, ion) could be linked with an im- countries.
only 100 people per one million balance of a chemical in the brain However, despite these occasional
population were diagnosed as being called serotonin. slaps across the wrist, manufacturers
depressed; today, this figure now SmithKline Beecham, the manu- are generally allowed to continue
stands at 100,000 people per million facturer in the US of the SSRI Paxil promoting the hypothesis.
population (Healy D. Let Them Eat Prozac. (paroxetine), has this to say on its
New York: NYU Press, 2006). website: Scientific evidence sug- The SSRIs dont work
The depressionserotonin hypoth- gests that depression and certain Not surprisingly for drugs based on a
esis has been actively promoted by anxiety disorders may be caused by false hypothesis, they arent effective.
drug companies in advertisements a chemical imbalance in the brain. In a recent meta-analysis of 74 trials
to both doctors and the general Paxil helps balance your brains involving 12 antidepressants that
public, and in seminars to health chemistry. had been logged with the FDA,
professionalsand so successfully The idea is repeated constantly by researchers from the Oregon Health
that it has been widely accepted as SSRI manufacturers, even though the and Science University discovered
a physiological fact. In the US, where US drugs regulatory body, the Food that the manufacturers either tried
drug companies are permitted to and Drug Administration (FDA), has to hide the fact or put a positive spin
market directly to consumers, sent out 10 warning letters to them on any results that suggested that

12 WDDTY Dangerous drugs

their drug was not helpful.
As for 22 studies that had negative Treating depression without drugs
results, the researchers found that
none of them had been published, There is a range of strategies that can be adopted to help to overcome
while a further 11 reported positive depression, depending on its severity, and they dont involve the use of
conclusions that were not backed toxicor dubiousdrugs such as the SSRIs.
up by the research findings. Of the u St Johns wort (Hypericum perforatum). This herb, dubbed Natures
published trials, 94 per cent were Prozac, is a proven remedy for mild-to-moderate depression, although it
positive, suggesting that the drug has also proved effective in more severe cases. In Germany, it has become
was considerably better than a the standard treatment for depression, and is even preferred over
placebo in treating depression. Yet, antidepressant drugs. Numerous studies have shown that the herb works.
the FDAs analyses of the same trials One found that 300 mg three times a day cured 75 per cent of depressed
concluded that only 51 per cent people (J Geriat Psychol Neurol, 1994; 71: 124). Doctors in the UK and Ireland
presented positive findings (N Engl J have been opposed to the herb only because it can interfere with
Med, 2008; 358: 25260). prescription drugs.
In a separate analysis of clinical u Diet. Oily fish can ease depression. Tryptophan-rich foods, such as turkey,
trials involving SSRIs submitted to salmon and dairy, may also help, as may foods rich in vitamin B6, including
the FDA, researchers discovered that soy-beans, lentils, meat, poultry, fish, fruit and brown rice. Make sure that
a placebo, or sugar pill, replicated up you consume plenty of mono- or poly-unsaturated fats, and cut out caffeine
to 80 per cent of the benefits of the and refined sugar, and eat only dark chocolate.
so-called active agent, and that 57 u Nutrition. The B-complex vitamins, including B12 and folic acid, can help
per cent of all trials, published and with depression, as can calcium, zinc and the omega-3 essential fatty
unpublished, failed to demonstrate acids.
any statistically significant u Thought Field Therapy. The TFT technique involves finger tapping on
differences between the drug and a specific acupuncture points around the body at the same time that the
placebo (Prev Treat, 2002; 5: article 23; patient is generating a negative thought or emotion. The tapping is
online at supposed to release the trapped emotion. However dubious it may sound,
pre/5/1/23). the therapy has been tested in several trials, and the early results are
Other drugs and remedies for promising.
depression appear to work just as u Cognitive behavioural therapy. This form of talking therapy, which is
well asif not better thanan SSRI based on the idea that how we think, act and feel all interact with each
drug, which serves to further other, is one of the most successful ways to treat mild-to-moderate
challenge the depressionserotonin depression. Its as effective as SSRI drugs, but without the dangerous side-
hypothesis. A Cochrane review of effects (BMJ, 2006; 332: 10302).
various antidepressants found that u Exercise. Exercise can be surprisingly effective in combating depression.
there was no major difference in Even moderate exercise, which involves just walking briskly or jogging for
effectiveness between SSRIs and 40 minutes, three or four times a week, can help. Those who already
tricyclics, an older class of anti- exercise regularly are less likely to become depressed. One study found
depressants that was developed in that moderate exercise was as effective as the powerful SSRI sertraline
the 1950s (Cochrane Database Syst Rev, (Zoloft) (Arch Intern Med,
2000; 3: CD002791).
In randomized trials, bupropion
(Wellbutrin; Zyban), an antidep- effective a remedy against depression The risk was thought to be
ressant that is more commonly used when pitted against Zoloft in a greatest among adolescents and
today as a stop-smoking drug, and randomized trial of older patients teenagers, but the FDA has admitted
reboxetine (Edronax; Norebox) were with severe depression (Arch Intern Med, that anyone who takes an SSRI is at
found to be equally as effective as 1999; 159: 234956). greater risk of committing suicide.
SSRIs for treating depression and, At an FDA drugs advisory com-
yet, neither interferes with serotonin SSRI dangers mittee meeting held in December,
levels (J Clin Psychiatry, 1997; 58: 5327; J The FDA has issued more public 2006, psychiatrist Dr David Healy
Clin Psychiatry, 2000; 61 [Suppl 10]: 318). warnings and black-box notices told the members: The idea that you
The herbal remedy St Johns wort prominent announcements in the would have a risk in one age group
(Hypericum perforatum) was more drugs literature and patient infor- but not in another is just wrong.
effective than an SSRI in one trial mation sheetsregarding the Another psychiatrist, Dr Peter
involving patients with moderate-to- dangers of SSRIs than for almost Breggin, also testified, and said:
severe depression (BMJ, 2005; 330: 503), any other family of drugs. Although Americas drug watchdog needs to
and the SSRI sertraline was even the drugs come with a vast array of come clean because its been approv-
bested by a placebo in another trial adverse reactions, drugs regulators ing depressants as antidepressants.
involving patients who were severely are especially concerned over the The primary data on suicidality has
depressed (JAMA, 2002; 287: 180714). SSRI potential to increase the risk been generated in short-term
Indeed, exercise was just as of suicide. controlled clinical trials planned by

WDDTY Dangerous drugs 13

Drugs for depression
drug companies, carried out by drug Every SSRI manufacturer has Over the years, SSRIs have been
company hacks, and evaluated by active lawsuits pending. Forest Lab- prescribed for pain, insomnia,
drug company employees at cor- oratories, which makes Lexapro shyness, menstrual discomfort,
porate headquarters. If that kind of (escitalopram oxalate) and Celexa dementia and restless leg syndrome,
carefully cultivated evaluation bears (citalopram), has been involved in at and to every age group, including
such bad fruit, imagine what the real least 25 lawsuits recently, says US law young children, and even to preg-
data must show. firm Pogust & Braslow, and most of nant women, despite evidence that
Despite these very real dangers, these involve cases of unexplained these drugs are harmful to an
doctors continue to prescribe SSRIs suicide or attempted suicide. expectant mother as well as to her
to children. In one study, researchers fetus (N Engl J Med, 1996; 335: 10105).
discovered that children as young as Off-label prescribing While its not illegal for a doctor
six years of age were being prescribed One major cause of the enormous to prescribe a drug off-label, it is not
an SSRI, and they were 52 per cent success of the SSRIs has been off- allowed for drug companies to
more likely to commit suicide within label prescribing by doctorswhere promote a drug for such unapproved
the following two months. Overall, a they prescribe drugs either to people, uses, although it is known to be a
child on an SSRI was 15 times more such as the very young or very old, widespread practice and one that has
likely to kill himself than one not for whom no safety trials have ever been the subject of a US House
taking such a drug (Arch Gen Psychiatry, been undertaken, or for problems for Committee hearing.
2006; 63: 86572). which the drug has never been
In addition to the suicide risk, intended. Mind over matter
SSRIs have been linked to a wide Although the SSRIs are labelled as The SSRIs are some of the most
range of other adverse reactions. antidepressants, the FDA has allowed dangerous drugs ever developed and,
Prozac alone has 242 different side- their use as remedies for eight other yet, they are probably the least
effects listed, including 34 problems psychiatric disorders, including effective. Based on an hypothesis
of the genitourinary tract. In one social anxiety disorder, obsessive that stubbornly remains unproven,
review of drug reactions, it was found compulsive disorder (OCD) and pre- these agents usually fare little better
that during a 10-year period, Prozac menstrual dysphoric disorder (a than placebo, which suggests that
was associated with more hospital- severe form of PMS). any benefit while taking them is very
izations, deaths or other serious Despite such a loose definition of likely being generated by the patient
adverse effects reported to the FDA an antidepressant, one study found himself.
than any other drug in America that 75 per cent of all prescriptions Depression can be debilitating,
(Moore T. Prescription for Disaster. New York: for SSRIs were off-label, as treat- but it can be resolved without the use
Dell Publishing, 1998). ments for conditions for which the of these powerful, yet ineffect-ive,
The most common problems seen drugs have not been approved drugs. It may be that the most
with SSRIs are neurological (22 per (J Clin Psychiatry, 2006; 67: 97282). Lead important contribution of SSRIs has
cent), psychiatric (19.5 per cent), author Dr Hua Chen, from the been to our understanding of the
gastrointestinal (18 per cent) and University of Houston, said that the power and importance of our own
dermatological (11.4 per cent) (Drug findings reveal a significant gap in minds in bringing about health.
Safety, 1999; 20: 27787). the US drugs-safety system. Bryan Hubbard

14 WDDTY Dangerous drugs

The great Prozac conspiracy
After 20 years of these so-called miracle antidepressants,
psychiatrists are shocked to discover that drug
companies withheld information about the risks of this
class of drugsand with the tacit approval of the drug
t all started so promisingly, when by allowing the transmitting cell to

I drugs like Prozac first came on

the market in the 1980s. Here at
last, we were told, was a new class
of antidepressants that would
transform the world of psychiatry.
reabsorb them from the synapse (a
process that is called reuptake). So, if
a way can be found to stop (or inhibit)
this reuptake, the synapse would
remain constantly bathed in neuro-
Out would go the old dirty transmitters. But only one neurotrans-
psychiatric drugs of the 1950s, and in mitterserotoninis involved in
would come a set of drugs honed by depression, which means that only
science to target the biochemical core serotonin needs to be selectively
of depression in the brain. isolated from the rest of the neuro- quickly withdrawn from the market
These new drugs had a very transmitter cocktail. when patients developed Guillain
scientific-sounding nameselective So, in the mid-1970s, the pharma- Barr syndrome (a serious auto-
serotonin reuptake inhibitorswhich ceutical companies set themselves the immune condition involving damage
neatly morphed into the catchy task of finding a drug that would select to the peripheral nerves). Soon after-
acronym SSRIs. They are among the out serotonin, and inhibit its wards, a second SSRI, a French drug
most successfully marketed drugs in reabsorption by the transmitting called indalpine, was also stopped after
history, so much so that the brand neurones. Ten years later, the family of it was found to damage blood cells.
leader Prozac is almost a synonym for SSRIs was created. These straws in the wind didnt
antidepressants, just like Hoover is for The first SSRI appeared in the mid- deter other drug companies, however
vacuum cleaners. 1980s from the Swedish pharma although the SSRIs hoped-for lack
But now, some two decades later, company Astra. The drugs chemical of side-effects had been intended to
the world of psychiatry has finally name was zimelidine, but it was be a major part of their sales pitch.
discovered it has been largely taken for
a ride with SSRIs, by both drug
companies and lax regulators. Safety and side-effects
Miracle science
In the brain, messages are passed In addition to suicide risk, SSRI side- when they yawn, often progressing
between brain cells (neurones) across effects include: to orgasm)
a tiny gap called a synapse. This gap Insomnia (up to 35 per cent of patients Akathisia, described by an SSRI
is filled with chemicals, which have need sleeping pills) spokesman as overwhelming dis-
the job of controlling the communica- Sexual dysfunction (anorgasmia in up tress and unbearable discomfort,
tion between brain cells, transmitting to 83 per cent of men; this may making patients feel like death is
information from one neurone to the be permanent, even after the drug a welcome result. It can some-
other. Hence, these chemicals are is withdrawn. In bizarre contrast, times be mistaken for worsening
called neurotransmitters. When one SSRIs can also cause yawning- depression, prompting some doc-
neurone communicates with its excitement syndrome, where pa- tors to increase the dosage (J
neighbour, it floods the synapse with tients experience sexual arousal Psychopharmacol, 1998; 12: 192214).
a cocktail of neurotransmitters, one
of which is serotonin. Other effects
By the 1970s, it had been dis-
covered that some prescription drugs Nausea Weight gain Mania
can cause depression as a side-effect, a Vomiting Lethargy Dizziness
problem traced to low brain levels of Diarrhoea Fatigue Problems in
serotonin. It was then argued that, if a Gastrointestinal bleeding Sweating urinating
way could be found to increase Headache Anorexia Trembling or shaking
serotonin in the brain, it would reduce Agitation Forgetfulness Dry mouth
depression. Nervousness Seizures Hostility
Its already known that the brain Rash Anxiety Aggression
naturally conserves neurotransmitters

WDDTY Dangerous drugs 15

Drugs for depression

The first SSRI to come to market

was fluvoxamine (see box, right), Patently profitable
but its manufacturer Solvay Pharma-
ceutical, based in Georgia, lacked
Generic (trade) names Manufacturer Patent expiry date
marketing clout, making its launch a
bit of a damp squib. citalopram Lundbeck 2002
It took the marketing power (Celexa, Cipramil, Emocal,
wielded by the giant US (and Sepram)
international) drug company Eli Lilly fluoxetine Eli Lilly 2000
to collar most of the SSRI public (Prozac, Fontex, Seromex,
relations when it launched fluoxetine Seronil, Sarafem, Fluctin)
in 1987, under the memorable trade- fluvoxamine maleate Solvay 1996
name Prozac. Newspapers were quick (Luvox, Faverin)
to swallow the companys sales pitch, paroxetine GlaxoSmithKline 2006
(Paxil, Seroxat, Aropax,
with headlines describing Prozac as a
happiness pill. Even normally cynical
sertraline Pfizer 2005
journalists described Prozac as a (Zoloft, Lustral, Serlain)
valuable, quick, emotional fix, and a
panacea for the stresses of the 20th
century. witness Dr David Healy, of Bangor every antidepressant licensed since
But the marketing dream soon University in North Wales, told the 1987 [showed] an excess of suicides.
turned into a PR nightmare as patients court he had uncovered early Smith- The companies, he said, had
began to complain of unpleasant side- Kline Beecham documents which obscured the suicide evidence by
effects such as nausea, sexual dys- acknowledged that serious symptoms fudging the data, a practice
function, insomnia and gastrointes- of agitation could occur after taking euphemistically referred to as
tinal bleeding. Worse, Prozac some- the drug for just a few days. recoding.
times caused violent, irrational When Healy challenged Pfizer
behaviour. In one infamous case, a Whistleblower (which makes sertraline, marketed as
middle-aged factory worker became Dr Healy, now a professor of psychia- Zoloft) and GSK with his bombshell
homicidal while taking Prozac, killing try at the North Wales Department of discovery, they didnt deny that
five people and wounding 12 others at Psychological Medicine, has recently recoding had occurred, but noted that
his workplace. been in the news again, after the FDA [Food and Drug Adminis-
In another example of horrific publishing an article in the scientific tration, the US watchdog regulatory
behaviour as a result of taking this literature accusing drug companies body] has neither criticised these data
drug, a female patient attacked her and their official regulators of dirty or the report as inappropriate, nor
mother by biting her so viciously that tricks (BMJ, 2006; 333: 925). required additional analyses.
she managed to rip away 20 chunks of The target of his concern was the However, documents obtained
her mothers flesh. Eli Lilly was fact that the drugs cause some people under the Freedom of Information Act
ordered to pay substantial damages. to commit suicide: indeed, these reveal that FDA regulators were fully
After SmithKline Beecham (now highly sophisticated drugs apparently aware of the recoding but, says Healy,
GlaxoSmithKline or GSK) weighed in can precipitate the fatal behaviour told the pharma industry that they did
with their own SSRI, Seroxat (parox- that psychiatrists spend their lives not see the SSRIsuicide connection
etine), similar side-effects were seen trying to prevent. as a real issue, but rather as a public
with their drug, too. Even doctors The first warnings of this effect relations problem.
began to express some concerns. were sounded as early as 1991, when And yet, no fewer than four clinical
Physicians are seeing long-term side- researchers looked at the placebo- studies published between 1990 and
effects from SSRIs far in excess of controlled clinical evidence for 2000 have shown SSRIs to cause an
what was expected from the clinical fluoxetine, and discovered a spike of increased risk of suicidality,
trial data, Dr Norman Sussman, a suicides (BMJ, 1991; 303: 68592). culminating in a British report
psychiatrist at New York University Drug companies glossed over such entitled Deliberate Self-Harm and
Medical Hospital, told the press in findings, and even complained that Antidepressant Drugs. This was a
1998 (Clin Psychiatr News, 1998; 26: 1). placebo-controlled trials were survey of the Accident & Emergency
Within a few years, Seroxat was unethical, as SSRIs were self-evidently case notes from one UK hospital area
following Prozac into the courts. In both effective and safe. However, as that revealed a five-and-a-half times
June 2001, GSK was ordered to pay Professor Healy revealed in his British extra risk of suicides among people
$6.4m to the family of Donald Schell, Medical Journal article, he obtained taking SSRIs (Br J Psychiatry, 2000; 177:
who, after just two days on Seroxat, access to some of the original drug- 5516).
killed his wife, daughter, grand- company data, which gave the lie to
daughter, and finally himself. Although their official PR line. He was able to Slow-acting regulator
GSK tried to claim that the drug confirm that, in the evidence Healy showed that there has been
wasnt to blame, the British expert presented to the licensing authorities, collusion between the authorities and

16 WDDTY Dangerous drugs

the drug companies in putting as good the suicide problem. His own analysis aged two to 19 tripled in just the 10
a gloss on the data as possible. shows that the latest data for years from 1988 to 1998from 40
For example, the FDA had a back- paroxetine indicates as much as a million prescriptions to 120 million
door agreement with Pfizer that the fivefold increase in suicide risk, a after the introduction of fluoxetine
sertraline suicide data should be statistic consistent with previous (Pediatrics, 2002; 109: 7217).
analysed as if it were a constant findings. Equally surprisingly, very few SSRIs
hazard, even though they knew the Another area of concern is children. have actually been formally licensed
evidence clearly shows that suicides Astonishingly, SSRIs have been given for use by children, so all of this
peak in the first few weeks of use. to kids as young as two years old, and prescribing to them has been off-
This averaging-out is outright the figure is rising exponentially for label. This term is used to describe
manipulation of data, says Healy, older children, too. For example, when doctors prescribe drugs that
because it disguises the true extent of sertraline prescriptions for youngsters have been officially approved for one
purpose to treat other, unauthorized
In fact, few drugs are ever tested
What to do instead on children. The reasoning behind this
practice is that children are simply
Allergies, food intolerance and nutritional deficiency all cause depression. So, first little adults, so the hazard profile of
ensure that you are receiving the nutrients you need by taking the following a drug may safely be applied to them
nutritional supplements: so long as the appropriate reductions
u good vitamin B-complex, one which contains 50 mcg of B12 and biotin, 400 in dosage have been made to
mcg of folic acid and 50 mg of all other B vitamins accomodate their smaller size.
u Vitamin C, 500 mg twice a day But this is not necessarily true. For
u Calcium, 500 mg/day and magnesium, 200 mg/day (both necessary for nerve example, Ritalinthe infamous hyper-
function). One recent study showed rapid recovery (less than seven days) activity drugappears to act as a
from major depression with magnesium supplements (Med Hypotheses, 2006; 67: depressant in children, but is a
36270) stimulant when taken by adults.
u 5-HTP (plant-based tryptophan), 200 mg/day. When compared with So we know that children can react
fluvoxamine, for example, 5-HTP is at least 10 per cent better at reducing totally differently from adults, partic-
depression, anxiety, insomnia and physical symptomsand works faster, too ularly when mood-altering drugs are
(Psychopathology, 1991; 24: 5381) concerned.
u Zinc, 15 mg/day Indeed, in the case of SSRIs, it was
u Omega-3 essential fatty acids (EFAs; for example, cod liver oil)) 2 g/day, or largely childrens violently self-
EPA (eicosapentaenoic acid) 1 g/day. In one study, taking EFAs for just 12 harming reactions to the drugs that
weeks reduced depression by half in patients for whom all conventional drugs alerted psychiatrists to the suicide
had failed (Arch Gen Psychiatry, 2002; 59: 9139) problem in the first place.
u St Johns wort, 300 mg three times a day. A meta-analysis of 23 studies In 1991, Yale University doctors
showed this herb to work in mild-to-moderate depression, and to be just as reported the case notes of six children,
effective as the standard drug treatments, but with fewer adverse side-effects aged 10 to 17, who developed intense
(BMJ, 1996; 313: 2538). Check that the tablets contain a standardized content self-injurious ideation or behaviour
of 0.3 per cent hypericin (the major active ingredient in St Johns wort), as well while taking Prozac. For example, after
as 5 per cent hyperforin, recently discovered to be another key natural three weeks on the drug, one 14-year-
ingredient (Pharmacopsychiatry, 1998; 31 Suppl 1: 549). Choose solid tablets as old girl, who had never been suicidal
they have a much longer shelf-life than capsules. before, began cutting and otherwise
Other alternative treatments include: injuring herself. She told hospital staff,
u Exercise. Get your body moving. A German study showed that 30 minutes Im just waiting for the opportunity
of treadmill exercise a day helped reduce major depressive episodes in to kill myself, and chanted, Kill, kill,
100 per cent of patients, of whom more than half experienced substantial kill; die, die die; pain, pain, pain (J Am
improvement. The benefit was particularly marked in people for whom Acad Child Adolesc Psychiatry, 1991; 30:
antidepressant drugs had failed (Br J Sports Med, 2001; 35: 1147) 17986).
u Acupuncture. A recent Chinese study compared acupuncture head-to-head Another study carried out 10 years
with Prozac. Acupuncture was found to be superior as it worked much faster, later again found that SSRIs increased
and the only side-effect was mild fatigue (J Tradit Chin Med, 2005; 25: 2436) suicidal behaviour in children (J Am Acad
u Thought Field Therapy (fingertapping on acupuncture points). TFT has been Child Adolesc Psychiatry, 2001; 40: 13645).
found to cut symptoms of emotional distress by 50 per cent (Traumatology, 1999; And yet, it wasnt until 2003 that
5: 1, article 4) the British Medicines and Healthcare
u Light therapy. Choose a light box with an output of at least 10,000 lux, and use Products Regulatory Agency (MHRA)
it for 30 minutes between 7am and 9am. A recent clinical trial pitted light finally recommended that SSRIs not
therapy against Prozac, and found that the drug worked no better be given to childrenand this only
(Am J Psychiatry, 2006; 163: 80512). after being shamed into action by
media reports of teen suicides caused

WDDTY Dangerous drugs 17

Drugs for depression

by Seroxat. facturers. evidence that they dont work:

Why did they take so long? But those claims have since turned We learned that pharmaceutical
According to Healy, there were two out to be highly optimistic. Study after companies selectively released data
main reasons: a lack of statistical study has shown that SSRIs are that reflected positively on their
expertise on the part of the MHRA actually little better than the TCAs. products, and that combining sup-
(and the FDA, too); and a mindset Recently, researchers have pulled pressed and published data suggested
which overstates the benefits and together 15 to 20 years worth of that most of these medications had
underestimates the risk of drugs. statistics, including previously sup- questionable efficacy (J Clin Psychol,
As a result, both the British and pressed data amassed by the drug 2006; 62: 23541).
the American regulatory bodies, he companies themselves, as a sort of Any residual confidence in the
says, insist on such cast-iron statistical final overall verdict on the SSRI SSRIs is now likely to be permanently
proof of harmful effects that they experience. eroded. However, most of the large
demand an all but unreachable These huge clinical meta-analyses pharmaceutical companies that
threshold. have looked at SSRI use by a variety of produced the SSRIs will not receive
The crowning irony of this official patient groups. Here, for example, are any negative fallout on their share
intransigence came in May of this year, direct quotes from what researchers prices. After all, most of the SSRI
when GlaxoSmithKline themselves have found in three different types of patents have now expired (see box,
sent a letter to doctors, warning them patients: page 16). So, it would seem that the
that paroxetine could cause a sixfold u people with mild depression: . . . drug giants have already made
increase in the risk of suicidesa no differences between TCAs and whatever money they can and can now
figure that neither the FDA nor the SSRIs (Cochrane Database Syst Rev, do a runnera kind of smash-and-
MHRA has so far acknowledged. 2000; 4: CD001130) grab raid on the world of psychiatry.
Many people expect drug com- u depression in general: There are Nevertheless, their future share in
panies to be slow to concede that a no clinically significant differences this lucrative market may be
drug causes hazards, commented in effectiveness between SSRIs and damaged. Pharma-industry analysts
Healy dryly, but we do not expect TCAs (Cochrane Database Syst Rev, warn that the world antidepressants
our regulators to be even slower. 2000; 2: CD001851) market is in serious trouble, with
u The elderly: . . . SSRIs and TCAs revenues of only $7 billion a year
Major side-effects are of the same efficacy (Cochrane 50 per cent down from their peak (The
Excess suicides are just the beginning. Database Syst Rev, 2006; 1: CD003491). World Market for Antidepressants, 2006).
There are also major issues of side- So the truth is finally revealed: SSRIs They also predict that the world
effects and efficacy. After 20 years of have never worked any better than the market will crash, mainly because
experience with SSRIs, it now turns drugs they were intended to replace. there are not enough new anti-
out that these super-sophisticated The anger in response to this depressants in the pipeline.
drugs that were once hoped to be revelation among the psychiatric That may indeed be so, but the
relatively free of side-effects are, in profession is now palpable. Even market may also crash for at least
fact, potentially more dangerous than normally conservative medical jour- three other reasons, too. The trust
the crude tricyclic antidepressants nals have spoken out against the that may have existed between
(TCAs) of the 1950s they were meant drugs. An article in a major psychiatric psychiatrists and their patients and
to surpass (see box, page 15). journal recently concluded that drug- the pharmaceutical companies is
But the SSRI scandal stretches even company-sponsored research is no likely to be permanently tarnished.
beyond that. The only reason SSRIs longer reliable: Caution is needed in With this whole sorry episode, the
were allowed onto the market in the interpreting drug company sponsored biochemical model of depression
first place was that the drug com- trials given the evidence of selective and biochemical manipulation as a
panies claimed they were far superior reporting and publication bias (Curr solutionis now in question. The
to the existing TCAs. In the heady days Opin Psychiatry, 2005; 18: 215). result is that patients may be more
of the 1980s, figures of 80 per cent Similarly, another peer-reviewed willing to turn to the many safe,
effectiveness were confidently bandied journal revealed that, if the true data natural antidepressants that are
aboutthis was three times better for these drugs had not been available to them.
than with TCAs, said SSRI manu- suppressed, it would have served as Tony Edwards

18 WDDTY Dangerous drugs

SSRIs: bad prescribing habits
ust when it seemed as if it in that first week (Arch

Gen Psychiatry,
couldnt get any worse for 2006; 63: 121723).
manufacturers of antidep- This result jibes with the new
ressants like Prozac, new neuroscience about the brain, which
evidence reveals that they havent been has found that the longer depressive
correctly prescribed since their release thoughts remain unchanged in the
on the market. brain, the more likely they are to
Thousands of patients are being put become hardwired in and the less
at risk of life-threatening side-effects, likely is the person to respond to
including an increased risk of acts of conventional treatment.
self-harm such as suicide, because they So worrying is this new finding that
are being given the drug beyond the the US drugs watchdog, the Food and
point where it will do any good. Drug Administration (FDA), has now
New evidence shows that, if the issued a blanket mandate, instructing
drugs are going to have any benefit all manufacturers of SSRIs to update
at all, it will happen within the first their black-box warnings. The new
two weeks of taking the drug. Conse- labelling must now include the warn-
quently, many patients are being put ing that young adults aged from 18
at risk of lethal side-effects because to 24 taking these drugs may increase
the drug companies and doctors are the years the SSRIs have been on the their risk of suicidal thinking and
recommending that the drugs be taken market. behaviour, even during initial treat-
for at least six weeks, if not longer. However, after many years, the mentthe first month or two. Manu-
The conventional wisdom about the science has begun to challenge this facturers of all SSRIs are being given
new antidepressants holds that it takes basic assumption. A 2005 review of just 30 days to submit revised product
a little time for them to work. 76 double-blind, placebo-controlled labels and medication guides to the
According to recent guidelines issued studies of antidepressants discovered FDA for review.
by Britains National Institute for that nearly two-thirds of the improve- The new labelling follows quickly
Health and Clinical Excellence (NICE), ment seen in patients took place within on the heels of the 2005 black-box
. . . patients started on antidepress- the first two weeks. Half of all patients warnings issued by the FDA, which
ants should be informed about the who responded to the drug within a warned of the increased risk of suicide
delay in onset of effect. six-week period did so during the first among children and adolescents. At
This was certainly the clinical and fortnight (Am J Psychiatry, 2000; 157:1423- that point, the FDA asked that
laboratory experience with the older 8). manufacturers include in the warning
tricyclic antidepressants. The drug Then, a review of the major placebo- that all children and teenagers be
companies and scientists believed that controlled studies of SSRIs cast even closely observed and monitored while
this early generation of drugs worked more light on the timing of therapeu- taking the drugs. Furthermore, SSRI
quickly until the research proved tic benefit. This meta-analysis showed drug companies were asked to develop
otherwise. Animal models showed that that the greatest period of therapeutic medication guidesFDA-approved in-
the drugs only worked once the ani- response occurs within the first week formation packs for patients and their
mals (and, it was assumed, human and that benefit declines with every families to be handed out with each
patients) had developed an insensitivity week thereafter. In fact, one-third of new prescription or refill. These guides
in certain brain receptors. the full effect of treatment is apparent were designed to be user-friendly and
A review of all of the studies in the
scientific literature also confirmed a
delay in the time it took the drugs to
Signs of SSRI-induced suicidal impulses
start kicking in (Arch Gen Psychiatry, 1984;
41: 7826). In addition, many of the The following symptoms have all been reported by both adult and paediatric
sophisticated theories concerning how patients taking antidepressants. Although a causal link between these side-
selective serotonin reuptake inhibitors effects and suicidal impulses has not yet been established, the FDA is
(SSRIs) worked all stressed this delay concerned that they may be precursors to a drug-induced desire to kill
in onset. oneself.
Then, when the SSRIs were first v Anxiety v Aggressiveness
launched, psychiatrists and researchers v Agitation v Impulsivity
simply assumed the same delay would v Panic attacks v Akathisia
occur. The assumption of a lengthy v Insomnia (psychomotor restlessness)
time between the start of treatment v Irritability v Hypomania
and any actual effect underpinned the v Hostility v Mania.
prescribing habits of doctors for all

WDDTY Dangerous drugs 19

Drugs for depression
easily comprehensible by non-medical 14 additional cases of suicidal impulses risk of drug-induced self-inflicted
people, and to improve monitoring of per 1000 in those under 18. The death.
symptoms. FDAs Psychopharmacologic Drugs The FDA is quick to add that the
However, after this latest bombshell, Advisory Committee concluded that scientific data to date does not show
the FDA itself decided to examine new labelling changes were necessary an increased risk of suicide among
whether adults also faced any similar to inform healthcare professionals that those aged over 24. Indeed, it appears
risks. The agency began its own review young adults, as well as teenagers and that adults over 65 taking antidepress-
of nearly 3000 antidepressant studies, children, also face suicide risk with ants decrease their risk of suicidea
which included more than 77,000 these antidepressants. benefit that will be highlighted in the
adults taking SSRIs. At the end of last This new information about SSRIs new black-box warnings.
year, the evidence was in. The studies calls for a drastic revision of the use One can only guess whether this last
showed that there were five additional of SSRIs. Patients should only be given bit of received wisdom will also be
suicides or suicidal impulses for every these drugs for, at most, two weeks. undermined by evidence unearthed at
1000 young adults studied. An earlier Thereafter, doctors are needlessly a later date.
study showed that the drug causes exposing their patients to an increased Lynne McTaggart

20 WDDTY Dangerous drugs

SSRIs: Its not addiction,
its discontinuation syndrome
Call it what you will, but these drugs can still lead to
dependence and withdrawal symptoms

ollywood celeb Lindsay docs/en/d/Js4896e/ 9.html). In other

H Lohans admission to
a Los Angeles court
last month that shes
addicted to antidepressants reopens
a controversy that the drugs industry
words, give the problem a different
name, and it will throw everyone off
the scent.

The depressing reality

has tried to keep under wraps for 30 Call it what you like, the reality
years. remains the same: SSRIs are highly
After the hearing, Lohans father addictive. The independent Uppsala
Michael told journalists: These Monitoring Centre database lists three
drugs are killing my daughter and SSRIsfluoxetine, paroxetine and
killing millions of kids in America, sertralineamong the 30 highest-
and someone has to stop it. ranking drugs for dependency (www.
But, so far, no one has succeeded. Of
Not even a US Senate hearing in these, paroxetine is cited as the most
2007 could force an admission from addictive of them all (
SSRI makers that their drugs are uk/2/hi/health/1382551.stm). and short-lived, the packaged inserts
addictive. Claims of paroxetines addictive admit that withdrawal reactions can be
The drugs industry has played a qualities have dogged its manufacturer intolerable, with symptoms such as
damage-limitation game ever since GlaxoSmithKline (GSK) from the time dizziness, electric-shock effects, sweat-
Eli Lillys first SSRI, Prozac of its launch in 1992. GSK has always ing, nausea, insomnia, tremor, confu-
(fluoxetine), was approved in 1977. It maintained that its SSRI is not habit- sion, nightmares and vertigo (BMJ, 2005;
heralded a new family of drugs based forming and that, at worst, around 2 331: 824). Sexual dysfunction, such as
on the idea that depressed people are per cent of patients might suffer from loss of libido and impotence, is also
low in sero-tonin, a brain chemical discontinuation syndrome. However, common (J Sex Med, 2008; 5: 22733).
that acts on the nervous systema secret company papers from 1997 But all this downplaying, aided and
theory that has never been proven showed that 62 per cent of patients abetted by psychiatrists, keeps drug
(see box, page 22). were addicted to the drug (Ann Neurol, sales high, with global revenues in
2008; 64: A79). 2008 of $11 billion. Wyeths Effexor
Whats in a name? The US drugs monitoring agency, (venlaxafine) leads the field with a 36-
The first indications that SSRIs were the Food and Drug Administration per-cent share of the total market and
addictive appeared in 1992 for (FDA), issued a warning about the annual sales worth $3.93 billion (www.
fluvox-amine (Br J Psychiatry, 1992; 160: drug in 2002 and, that same year, the
2834), and opened the floodgates to International Federation of Pharma- Market).
similar reports for paroxetine a year ceutical Manufacturers Association A major driver of salesat least in
later and, for sertraline, in 1994. accused GSK of misleading the public the USis direct-to-consumer (DTC)
In a move to deflect concerns and of breaching two codes of practice. advertising. There, drug companies can
about the SRRIs addictive qualities, Since 1992, around 5000 Americans advertise prescription drugs directly to
Eli Lilly coined the term have sued GSK for downplaying the the public. Also, as depression is often
discontinuation syndrome in 1996, drugs serious side-effects, while law- subjective, many people can be con-
a euphemism that started appearing suits citing similar issues have been vinced that they have it. As a result,
on packaged inserts in 2001. issued in the UK. In 2004, GSK settled $120 million of the $900 million spend
The World Health Organization charges of consumer fraud by paying on DTC in 2005 was dedicated to anti-
(WHO) was not impressed. SSRIs out $2.5 million. Legal discovery depressants. In 2001 in the month
are an example of how a conceptual uncovered a deliberate and systematic after the 9/11 attack on the World
confusion over terminology can suppression of unfavourable studies Trade Center, GSK doubled its DTC
affect proper reporting, inter- (Angell M. The Truth About the Drug Companies. advertising spend on paroxetine (CNS
pretation and communication of Random House: London, 2005). Drugs, 2009; 23: 10320).
adverse drug reactions related to Although drug companies maintain Depression was once a serious
dependence ( that discontinuation syndrome is mild clinical condition suffered by a small

WDDTY Dangerous drugs 21

Drugs for depression

minority, but its now a lifestyle disease

that many of us have from time to The drugs dont work
time, and SSRIs such as Prozac have
become our chemical friends. If the theory of chemical imbalance is false, it follows that SSRIs wont ease
Behind this is the assumption that depression, at least not beyond the placebo effect.
the drugs are safe and non-addictive. In fact, an analysis of 74 SSRI studies bears this out. Researchers found
Not so, says Dr David Healy, a leading that one-third of such studies were never published because the results
expert on antidepressants. He believes were so poor. Around 94 per cent of the papers that were published had a
that more than half of paroxetine users positive result. Yet, when researchers from the US Food and Drug
are physically dependent on the drug Administration (FDA) re-analyzed the findings, they found that the SSRI was
( effective in only half of the studies. These studies had been paid for by the
stm). manufacturer of the drug being tested (N Engl J Med, 2008; 358: 25260).
Safety is also an issue. GSK paid out Drug companies have an overly simplistic view of depression, which
$6.4 million after a man murdered explains the overall ineffectiveness of SSRIs, say researchers from the
three members of his family before Northwestern University Feinberg School of Medicine. Eva Redei, a
killing himself after taking paroxetine professor of psychiatry at Northwestern, says that antidepressants are
for just two days. In Australia, a judge based on two false claims: that a stressful life causes depression; and that
ruled that sertraline had caused a man depression is caused by a chemical imbalance.
to murder his wife and then attempt Redei believes that depression is in some way associated with the
his own suicide. Healy believes that one development and functioning of neurons, and only when this is properly
in 1000 people taking paroxetine could understood can an effective antidepressant be developed (Presentation at the
suffer from such suicidal thoughts. 39th Annual Society For Neuroscience Conference, October 1721, 2009, Chicago, IL).
Bryan Hubbard

22 WDDTY Dangerous drugs

Drugs for children

Kiddie killers
Many of the mainstays of modern medicine can damage children

n 12 October 2007, three of and narcotics being the main offenders.

O the worlds leading drug

companies voluntarily
withdrew a clutch of cold
and cough remedies for infants. This
announcement was made immediately
Ironically, to combat the ADRs, 73 per
cent of cases were treated with even
more drugs, according to the hospital
records (Drug Saf, 2004; 27: 81929).
Earlier this year, pharmaceutical
after a bombshell US Food and Drug chemists at the University of British
Administration (FDA) report showed Columbia, in Canada, audited toxic
that everyday childrens medications reactions to drugs among their nations
had caused over 120 deaths over the children. Their four-year survey revealed
last 37 years in the US alone. Most of that 61 per cent of ADRs in children
the victims were infants under the age were serious, with as many as 41
of two. In its defence, the drug industry (out of 1193) children actually dying
partly blamed parents for not reading as a result of drug side-effects. The
labels, thus inadvertently overdosing main culprits were isotretinoin (an
their children. anti-acne preparation), paroxetine (an
At another extreme, parents have antidepressant), methylphenidate (Rit-
not only been blamed, but sent to jail alin, the hyperactivity drug), amoxy-
because of drug side-effects (see box). cillin (an antibiotic) and valproic acid
These two extremes are merely the (an anticonvulsant used in epilepsy)
twin peaks of a huge iceberg. Doctors
have been warning us for years that
there are major problems concerning Whos the criminal?
childrens medications in general, a
situation that both the drugs industry u In November 1997, two-month-old Alan Yurko, born in a weakened state
and regulators have largely ignored. after a difficult pregnancy, suddenly stopped breathing. His father rushed

ADRs in children
the infant to a Florida hospital, where he died two days later. The hospital
accused the father of causing shaken baby syndrome (SBS); he was
In the last few years, a slew of medical subsequently convicted and sentenced to life imprisonment.
reports has revealed the damaging Appeals court lawyers asked Dr Al-Bayati to investigate, who says, The
effects of prescription drugs on hospital was at fault on two main counts: it failed to review the childs
children. Paediatricians across the medical notes, which showed a history of infections, and to take account of
globe have become aware that children the side-effects of the vaccines the baby had already received from the
are at particularly high risk of so-called family physician. Furthermore, the child was given high doses of sodium
adverse drug reactions (ADRs) from bicarbonate and heparin by the hospital itself, and it was those drugs which
relatively common medications. caused the cardiac arrest and internal bleeding. I was able to establish that
Among the first whistleblowers were these symptoms, which are similar to those of SBS, did not develop until
British researchers from Nottingham after the baby was admitted to hospital (Medical Veritas, 2004; 1: 20131).
University who, six years ago, complet- u In August 2005, two-month-old Averial was rushed to hospital by her
ed a major audit of the reasons given mother, and diagnosed as suffering from acute bronchopneumonia and
for childrens hospital admissions. They respiratory distress syndrome. Blood analysis suggested major infection.
found that a staggering one in 50 hos- Chest x-ray showed pneumonitis, and physical examination and body
pital admissions was because of ADRs, scans revealed no evidence of physical injury. The hospital gave her
and nearly 40 per cent of these were epinephrine (adrenaline), sodium bicarbonate, antibiotics and other drugs.
life-threatening reactions. As ADRs It was only then that skull and rib fractures were seen on the scans. The
are often worse in children than in baby died 11 days after admission. The post mortem found evidence of
adults, they constitute a significant bleeding both inside and outside the skull which, taken with the rib
public health issue (Br J Clin Pharmacol, fractures, was consistent with physical trauma. The girls 27-year-old father
2001; 52: 7783).
was accused of shaking his daughter to death and is currently awaiting trial.
Its a similar story in other countries, Dr Al-Bayati was called in. My investigation reveals that the infants
too. Three years ago, doctors did a six- bleeding, brain oedema and necrosis, and skull and rib fractures occurred
year audit of paediatric admissions in after she had been brought to A&E. These injuries were caused by the
Ohio hospitals. Again, a significant original infection and the medications she received in hospital (Medical
percentage was found to be due to Veritas, 2007; 4: 145269).
ADRs, with antibiotics, anticonvulsants

WDDTY Dangerous drugs 23

Drugs for children

(Can J Clin Pharmacol, 2007; 14: e45e57).

A considerably longer, 15-year sur- The main culprits
vey found that, in Swedish children,
the most frequent causes of adverse u Decongestants
reactions were vaccines and antibiotics. v Anything with codeine, dextromethorphan, carbinoxamine, ephedrine,
Again, children died808 out of pseudoephedrine, phenylephrine or brompheniramine (CDC MMWR Surveill
5771as a direct result of medication Summ, 2007; 56: 14)
(Pharmacoepidemiol Drug Saf, 2005; 14: 4939). v Cough suppressants containing hydrocodone can lead to serious illness,
This survey came hard on the heels injury, or death, says the FDA, which has issued a formal ban on most
of a more intensive Swedish study that (over 200) of these products (
tried to measure the reliability of drug- NEWS/2007/NEW01713.html)
reaction reporting in general. The v Withdrawn drugs: Dimetapp Decongestant Infant Drops, Robitussin Infant
researchers found that both doctors Cough DM Drops, Little Colds Decongestant Plus Cough, Pediacare Infant
and the reporting system were Drops Decongestant, Tylenol Concentrated Infant Drops Plus Cold and
particularly lax in recording serious Cough, Triaminic Infant & Toddler Thin Strips Decongestant.
drug side-effects. An intensive analysis u Antihistamines
of 1349 patient records from five v Anything with diphenhydramine, brompheniramine or chlorpheniramine
Swedish hospitals revealed an under- (Nonprescription Drug Advisory Committee Meeting, 2007-4323b1-02-FDA 10-01-2007).
reporting rate of as much as 86 per u Asthma drugs
cent. Of 107 patients whose symptoms v Inhaled corticosteroids can stunt growth, and may cause osteoporosis
had probably been caused by drugs, (J Allergy Clin Immunol, 2003; 112 [3 Suppl]: S140).
only 15 had ever been recorded as an u NSAIDs
ADR; the other 92 cases of drug toxic- v Ibuprofen, aspirin and paracetamol (acetaminophen) are a significant
ity had been totally ignoredand this cause of morbidity in children (Br J Clin Pharmacol, 2005; 59: 71823).
in spite of the efficient, state-run u Antibiotics
Swedish medical system (Pharmacoepi- v More than half of all antibiotics cause ADRs (Biomedica, 2007; 27: 6675)
demiol Drug Saf, 2004; 13: 4837). v These drugs are one of the leading causes of fatal ADRs in children (Arch
This suggests that the already Dis Child, 2002; 87: 4626)
substantial official rate of annual child- v Amoxycillin is one of the most common causes of ADRs (Can J Clin
hood ADRs is very likely far below Pharmacol, 2007; 14: e4557).
the true figures. Indeed, last year, u Behavioural drugs
researchers from the Drug Safety Unit v Ritalin causes headache, insomnia, anorexia and tachycardia (Curr Opin
at Southampton University completed Pediatr, 2002; 14: 21923).
a huge survey of ADRs across 12 u Vaccines
countries, and found that ADRs were v The most recent CDC report records 11.4 ADRs per 100,000 doses,
underreported by an average of an primarily in children under six, and 14.2 per cent of all reports were
incredible 94 per cent (Drug Saf, 2006; seriousincluding life-threatening illness, hospitalization, permanent
29: 38596). disability and death (MMWR Surveill Summ, 2003; 52: 124).
This means that, to get a real picture
of the situation, any official ADR
statistics should be multiplied by 20. tested and for patients in whom it doctors of potential off-label uses.
Yet, behind all these figures lies a hasnt been studied. Not surprisingly, some doctors are
stark and rather disturbing fact: most The drug industry uses two relatively feeling increasingly uneasy about the
prescription drugs have never been innocuous terms to describe this impact this is having on children.
tested to see if they are safe for children situation: off-label and unlicensed. There have been numerous studies to
or, indeed, if they actually work for The former refers to the use of drugs show that many of the medicines used
them. Less than 25 per cent of drugs for conditions not indicated in the in children are used off-label or are
can be advertised as safe and effective products license, including dosage, unlicensed for use in children, says
[for children], say the British Colum- type of medical condition and age of Professor Ian Wong, of the School of
bia pharmacologists. patient. Unlicensed refers to prescrib- Pharmacy, University of London. Some
How can the authoritiesor doc- ing a drug for types of patients, such people may see these children as
tors, for that matterallow children as children or the elderly, for whom it unknowing participants in informal and
to be given drugs that lack safety or has not been authorized. uncontrolled experiments (Drug Saf,
efficacy data for such patients? It Astonishingly, both uses are legal. In 2003; 26: 52937).
appears that as long as a drug has been the UK and rest of Europe, they are For decades, the pharmaceutical
approved by the regulatory authorities permitted under the Medicines Act of industry has argued that children
for at least one medical condition, it 1968 and EU Pharmaceutical Directive should be excluded from experimental
can be used for any other medical 89/341/EEC. In the US, the Food and premarketing clinical trials to protect
purpose. Doctors have carte blanche Drug Modernization Act of 1997 them from possible harm. However,
to prescribe any approved drug for confirms the longstanding practice, another motive may well be financial.
conditions for which it hasnt been even allowing drug makers to inform Clinical trials involving children are

24 WDDTY Dangerous drugs

both expensive and difficult to carry every three ADRs (Pharmacoepidemiol Drug vulnerable to ADRs in hospital. In fact,
out and, yet, the market for childrens Saf, 2004; 13: 14752). according to the Nottingham University
drugs is much smaller than that for The fact that GPs use drugs off-label researchers, as many as one in 10
adults. The end result is that children is somewhat understandable, given that children suffers ADRs as a direct result
given even ordinary drugs like pain- they are generally not in the vanguard of drug treatment received at the hands
killers are likely to be exposed to of research. However, Italian research- of hospital doctors (Br J Clin Pharmacol,
substances with no objective evidence ers found that hospitals, rather than 2001; 52: 7783).
of safety or efficacy, or riskbenefit GPs, are the chief offenders. After a
analysis. worldwide data search going back to Voices in the wilderness
One Swedish survey of its doctors 1985, they found that up to 80 per None of this will come as a surprise to
prescribing habits found that, on cent of hospital drug prescriptions Dr Mohammed Al-Bayati, a toxicologist
average, more than 40 per cent of the for children were either off-label or and pathologist, who fled Saddam
drugs prescribed to children were off- unlicensed. The drugs most commonly Husseins Iraq 30 years ago and settled
label and that these were more likely used were paracetamol (acetamino- in California. When he arrived in the
to cause serious ADRs than approved phen), cisapride, chloral hydrate and US, he was shocked to find an almost
drugs. In this case, anti-asthmatics salbutamol (Eur J Pediatr, 2005; 164: 5528). equally repressive regime in the guise of
were the most frequent category of Small wonder, therefore, that Western medicine. He was confronted
problem drug, causing almost one in children have been shown to be most with case after case of parents being

Non-drug treatments for childhood problems

Many children suffer adverse reactions when given drugs for u Sore throat
problems that can be treated with safer alternatives. But, do v Throat spray containing 15-per-cent sage (Salvia
consult a qualified practitioner before taking this route. officinalis) extract (Eur J Med Res, 2006; 11: 206); a similar
product is Echinacea Throat Spray, made by A. Vogel,
INFECTIONS Switzerland
u Bacterial and fungal v Slippery elm, as a pre-drug therapy
v Colloidal silver. Take care not to overdose: 100 v Do nothing, rather than use drugs like penicillin (BMJ,
mcg/day is safe for a child weighing 20 kg (Curr Probl 2003; 327: 13247).
Dermatol, 2006; 33: 1734) PAIN
v Tea tree oil. As effective as standard antibiotics for skin u Headache
infections, including MRSA (J Antimicrob Chemother, 2003; v Peppermint oil applied to the forehead and temples
51: 2416), although it may cause skin reactions. (Nervenarzt, 1996; 67: 67281)
u Colds v Acupressure (Digital Dissertation Abstracts, 1990; DAI-B 50/
v Echinacea (Lancet Infect Dis, 2007; 7: 47380) and vitamin C 12: 5890)
(Cochrane Database Syst Rev, 2007; 3: CD000980) v Self-hypnosis (Pediatrics, 1987; 79: 5937)
v Saltwater nose drops v Check for food allergy (J Pediatr, 1989; 114: 518)
v Inhaling steam from water containing Friars Balsam, a v Feverfew may work (Lancet, 1988: ii: 18992), although a
600-year-old herbal remedy. recent survey casts some doubt (Curr Opin Neurol, 2005;
u Coughs 18: 28992)
v EPs 7630, a herbal medicine from geranium (Pelar- v Homeopathy (although there are no clinical trials).
gonium sidoides) roots (Phytomedicine, 2007; 14 [Suppl 6]: u Toothache
6973), made by Schwabe Pharmaceuticals, Karlsruhe, v Oil of cloves
Germany; v Activated charcoal compress
v CORSHE-E, an Ayurvedic herbal linctus (J Herb v Tincture of Plantago major (plantain)
Pharmacother, 2004; 4: 112). A similar product is Olbas v Purple passion flower (Passiflora incarnata) for hyper-
Cough Syrup. sensitive teeth
u Urinary and bladder v Prickly ash (Zanthoxylum americanum) bark tincture
v Cranberry or blueberry juice (N Engl J Med, 1991; 324: to numb teeth and gums.
1599). u Colic
u Diarrhoea v See Q&A, page 19, for treatment alternatives.
v Individualized homeopathic medicine (Pediatr Infect Dis J, BAD BEHAVIOUR
2003; 22: 22934). v Remove additives from the childs diet (Lancet, 2007;
u Inner ear epub ahead of print; DOI:10.1016/S0140-6736(07)61306-3)
v Naturopathic herbal ear drops containing tea tree oil, v Check for food allergy in general (J Pediatr, 1989; 114: 518)
garlic and other herbs (Cochrane Database Syst Rev, 2006; v Pycnogenol, the extract from the bark of the French
3: CD005657) maritime pine tree (Eur Child Adolesc Psychiatry, 2006; 15:
v Individualized homeopathic medicine (Pediatr Infect Dis J, 32935)
2001; 20: 17783) v Omega-3 and -6 supplements (Pediatrics, 2005; 115:
v Homeopathic Pulsatilla (J Am Inst Homeop, 1986; 79: 34). 13606).

WDDTY Dangerous drugs 25

Drugs for children

prosecuted for killing their children, anaemia. for extended patents have been for
with some parents in jail and others But what about the rib factures? cardiovascular and other drugs that
even facing the death penalty. Looking How could they be explained? The are rarely prescribed in the paediatric
at these cases, one thing stood out child had a chronic cough, says Al- population, but for which an extra six
clearly to Al-Bayati: doctors, hospitals, Bayati. The child was already deficient months of exclusivity is very lucrative
prescription drugs and vaccinations in protein and vitamin K, which would in adults, wryly observe Dutch paedia-
were almost always involved in the cause weakening of the bones, and so tricians at the Erasmus University
childrens deaths. He soon found the childs ribs would be vulnerable to Medical Centre in Rotterdam (Eur Respir
himself defending parents as an expert any violent coughing (Medical Veritas, J, 2004; 23: 3103).
witness in the courts, sometimes the 2006; 3: 101940).
appeals courts (see box, page 23). Twenty years ago, Dr Al-Bayati was a Changes: too little too late
To date, Dr Al-Bayati has successfully lone voice in the wilderness but, today, Another major problem is that ADRs
defended over 20 cases in the US and theres now a huge groundswell of occur not just with prescription drugs,
Canada. His success has relied on concern within the medical profession but with everyday over-the-counter
exhaustive detective work, forensically itself. Its begun to realize that few (OTC) medicines, too, most marketed
drilling down into fine medical detail. drugs have ever been tested for for relatively trivial conditions.
One of his latest cases was that of use in childrenmainly because the On 1 October, the FDA issued a
Patrick, a three-month-old baby boy. In official drug-approval process only 356-page report on OTC decongestants
November 2005, he became severely requires evidence of safety and efficacy (cough and cold medicines) which
ill, and his parents took him to hos- in adults. Many doctors are now included the revelation that, between
pital. The hospital ran a battery of tests, clamouring for major reforms. 1969 and 2006, 54 children died after
and reported that the child had sub- The current situation regarding taking these medicines, and 69 died
dural and subretinal bleeding, seven rib the licensing of medicines for children after taking antihistamines. The report
fractures in various stages of healing, is a profoundly unsatisfactory state of admits that, since ADRs are under-
severe anaemia, thrombocytosis, low affairs both for children and their reported, those figures are likely to be
blood creatinine levels, hyperglycaemia, doctors, says Professor Peter Hill, of significant underestimates (Nonprescrip-
and elevated neutrophils and monocyte the Great Ormond Street Hospital for tion Drug Advisory Committee Meeting, 2007-
counts. The hospital doctors decided Children (Arch Dis Child, 2005; 90: i178). 4323b1-02-FDA 10-01-2007).
the child was suffering from shaken The practice of giving children drugs As we go to press, the FDA is
baby syndrome, and accused the meant for adults is being roundly reviewing whether the roughly 800
parents of having violently abused their condemned as unscientific guesswork. decongestants on the market are either
child. Says Professor Andrew Bush, of safe or effective for children. It has
The parents lawyers called in Dr Al- Londons National Heart and Lung already banned one group of cough
Bayati, who soon saw the gaping holes Institute: . . . the differences between medicines. Running for cover, manu-
in the indictment. The underlying adults and children, and at different facturers have now voluntarily with-
problem was that Patrick had always stages of childhood development, drawn another set marketed to infants
been a sick childborn prematurely, mandate strategies to improve this (see box, page 24). In September, the
and prone to vomiting and feeding situation rather than continually Consumer Healthcare Products Asso-
problems, leaving him malnourished. relying on extrapolation from adult ciation (CHPA), the OTC trade associa-
Two weeks before the hospital emer- studies . . . Disease phenotypes may be tion in the US, relabelled childrens
gency, the child had developed a severe completely different in children . . . decongestants, advising against their
cough, for which he was prescribed wheeze in infants is not miniature adult use in the under-twosalmost certainly
Tylenol. Five days later, the boy had asthma(Paediatr Drugs, 2006; 8: 2717). in response to a damning report seven
gastrointestinal reflux, for which he According to Professor Laura months earlier from the US Centers
was given Zantac, the antiulcer drug. Cuzzolin, of the University of Verona, for Disease Control and Prevention
Italy, there is a need to take immediate (CDC), which warned: Caregivers and
The underlying culprit action for a more rational use of drugs clinicians should be aware of the risk
For Al-Bayati, that was the root of the in paediatrics, to avoid exposing child- for serious illness or fatal overdose from
problem. Patrick was treated with ren and infants to unnecessary risks administration of cough and cold
Tylenol, he says, which contains (Fundam Clin Pharmacol, 2003; 17: 12531). medications to children aged under
acetaminophen, at a dose of 200 mg Regulatory authorities have finally 2 years (CDC MMWR Surveill Summ, 2007;
a daya high dose for such a young begun to act. In 2001, the US Food and 56: 14).
childand one that could cause liver Drug Administration (FDA) asked the But all this activity masks the
toxicity. The child was then treated with drug industry to provide specific underlying problem. With no safety or
Zantac (ranitidine), despite the fact paediatric safety and efficacy data for efficacy data, childrens medications
that ranitidine is known to potentiate any drugs prescribed to children, in as a whole are in chaos, and yet,
the toxic effects of acetaminophen. return for which the FDA offered six authorities appear to be paralyzed. In
Thus, liver poisoning partly explains extra months of drug-patent exclusivity. Europe in 2002, the EU published
the subdural and subretinal bleeding, Although the industry appeared to Better Medicines for Children as a
which was exacerbated by the childs have embraced this enthusiastically, prelude to new regulations for
inherent vitamin K deficiency and so far, virtually all the applications childrens medications, but has gone

26 WDDTY Dangerous drugs

no further. In the US, the FDA is only the authorities to act are almost
shutting the proverbial stable door, anguishedundesirable situation,
and then only to address a tiny part requires action and irrational are
of the problem. just a few of the comments. Doctors
This climate of regulatory dithering have rarely been so united against an
is deeply frustrating to many paedia- industry they so often perceive as their
tricians. WDDTY has collated a dossier lifes blood.
of over 30 medical reports about Meanwhile, thousands of children
childrens drugs written over the past are being injured by side-effects and,
decade. The pleas from doctors for in some of them, fatally.
Tony Edwards

WDDTY Dangerous drugs 27

Drugs for children

Puffers get blown out

The onetwo punch of steroids plus puffers for childhood asthma has
just been knocked out by new findings

ong-acting beta-agonists (or of seven reviews of LABAs as the

L LABAs), the standard-bearer

of treatment for childhood
asthma, have been found to be
not only useless as a chaser drug, but
also responsible for increasing the
primary or add-on therapyincluding
four reviews of the therapy in
childrenfound that inhaled ster-oids
plus LABAs led to a significantly higher
risk of adverse events vs steroids plus a
Salmeterol Multicenter
Research Trial (SMART), which
examined the safety of adding

incidence of serious asthma attacks in placebo. Although the two-stage salmeterol to a patients usual steroid-
children. therapy improved the need for rescue based asthma regime. Those taking the
So weighty is the evidence against medicine, nighttime awakenings and salmeterol suffered a significant
the drugs in this categoryincluding pulmonary function (as measured by increase in asthma-related deathfour
Glaxos Advair and Serevent, Astra- the blow test), the researchers times that of those taking a placebo.
Zenecas Symbicort and Novartis concluded, There is no clear benefit to This works out to one additional death
Foradilthat the US Food and Drug LABA in preventing asthma for every thousand patients. However,
Administration (FDA) had an advisory exacerbations in children (Evidence- the study did not include any patients
meeting in mid-December during Based Child Health, 2008: 3: 90919; online: 10 under age 12.
which FDA staff members recom- December 2008). In its advisory, the FDA warned that
mended withdrawing approval for all of The FDAs own meta-analysis of LABAs should not be used as a first-line
these drugs for children, and for 110 trials, involving nearly 61,000 treatment, or to relieve sudden
Serevent and Foradil for adults, too. The patients, found that, for every 1000 wheezing or wheezing that is growing
last two contain only LABAs, while patients treated with LABAs, 2.8 had a worse.
Advair and Symbicort combine them more serious asthma attack. Those at One reason why it took so long for
with an inhaled steroid. greatest risk appeared to be children problems with LABAs to surface is that
The FDAs move is a huge blow to aged 411 years, with blacks and conventional meta-analyses focus on
drug makers, as LABAs with steroids women also at higher risk than other single comparisons between drugs
have been the mainstay of asthma users. rather than on a number of analyses
treatment for children with persistent The FDA has been tracking beta- of different drug regimens to rank their
or severe asthma that fails to respond agonist problems since earlier this year, effectiveness.
to low- or medium-dose steroids. when the agency called for drug giants Indeed, a study using a networking
Indeed, some products such as Advair Glaxo, Novartis, AstraZeneca, Mylan meta-analytical technique attempted to
are fixed combinations of a LABA and Sepracor to provide clinical-trial do just that for the most commonly
(salmeterol) and inhaled steroid data demonstrating the safety of this used inhaled drug regimens for
(fluticasone). LABAs are also used class of drugs. reducing COPD attacks (BMC Med, 2009;
against exercise-induced asthma and The agency was first alerted in 2007 7: 2; doi:10.1186/1741-7015-7-2). It found
chronic obstructive pulmonary disease during a routine yearly review of that beta-agonists performed worse
(COPD). adverse/safety data for drugs approv-ed than all other regimes (long-acting
The FDAs sudden interest in this for children. For Serevent alone, the anticholinergics, inhaled steroids and
class of drugs represents a particular agency uncovered nine adverse-event combination treatments) in patients
blow to Glaxo, for which Advair is its reports in children and five deaths over with more serious forms of COPD, with
number-one bestseller. a 13-month period. the steroid/LABA combination only
LABAs are bronchodilators that The FDA had already set a black-box reducing exacerbations in those with
relax the muscles around the airways in warning in 2006 for salmeterol and milder disease.
the lungs that, when tightened up, Advair on the basis of findings from the Lynne McTaggart
cause wheezing or bronchospasm.
LABAs are said to relax constricted
airways for 12 hours or longer, and so
Beware of these long-acting puffers
are often used for moderate-to-severe
u Serevent Diskus, a disk-shaped inhaler that pumps out salmeterol
asthma and particularly to prevent
u Advair Diskus, which combines salmeterol with the inhaled steroid
nighttime episodes.
fluticasone, also delivered via a disk-shaped device
Nevertheless, regulatory bodies have
u Foradil Aerolizer, a puffer containing the LABA formoterol
begun to realize that, although LABAs
u Symbicort, AstraZenecas combo drug, mixes formoterol and the
reduce the frequency of asthmatic
inhaled steroid budesonide.
episodes, they also have a rebound
To find alternatives to puffers that can help respiratory problems, consult
effect in that, when episodes do occur,
The Asthma Manual, now available as an e-book ( or at
they are more severe.
A recent Cochrane Library overview

28 WDDTY Dangerous drugs

The kiddie upper takes a tumble
f Ritalin is the Miss America whether the problems merit a black-

I of the ADHD drugs, then

Dexedrine is the runner-up. When
Ritalin doesnt work, doctors
usually prescribe one of several
amphetamines such as Dexedrine,
box warningthe agencys strongest
classification of warning.
The new boxed warning also points
out that amphetamines have a high
potential for abuse, that prolonged
Adderall or Dextrostat. prescription may lead to drug depend-
Dexadrine used to be the ence and must be avoided and that
recreational upper of choice for the drugs should be prescribed or
everyonefrom students cramming dispensed sparingly.
for an exam to overworked Hollywood The FDAs decision, following the
starletsuntil it was vastly misused recommendations of two independent
and discredited as a largely review panels, has shocked American
recreational drug that was known on doctors who, up until now, have handed taking stimulant drugs at the regular
the street as speed, another one of out these drugs to all comers. The FDA prescribed dosage for ADHD. Although
mothers little helpers. estimates that one million adults and the FDA and medicine itself readily
Then ADHD (attention-deficit/ two million children refill a prescrip- admits it doesnt understand how great
hyperactivity syndrome) gave Dexe- tion for an ADHD drug every month. a role is played by these drugs in
drine a new lease on life. ADHD is A national study among American causing these effects, it warns that any
listed as its number-one indication for children by New York Universitys Child adult suffering from heart problems of
children between ages three and 16; Study Center discovered that about any variety should not be taking
the drug is routinely prescribed by one in seven of the parents of school- stimulants.
family doctors if Ritalin (methyl- age children reported giving their According to GlaxoSmithKline
phenidate) doesnt do the trick. children this type of daily psychoactive (GSK), stimulant drugs cause an
This cozy position is set to change medication. increase in blood pressure of 24
with a recent requirement by the US The new label warnings alert parents mmHg and an increase in heart rate
Food and Drug Administration (FDA) that sudden death has resulted from of three to six beats per minute. All
that Ritalin and the Dexedrine-type this type of central-nervous-system patients taking stimulant medication
drugs must now issue a warning on stimulant treatment at ordinary are now to be monitored, according to
their labels, explaining that the drug dosages in both children and the new warnings. Anyone suffering
can cause sudden death and serious adolescents with structural cardiac from hypertension, heart failure, a
cardiovascular adverse events. There abnormalities or other serious heart recent heart attack or ventricular
have been reports of children with problems. These include cardio- arrhythmias is now being advised to
heart trouble dying suddenly while myopathy (weakening of the heart avoid this class of drugs.
taking the drug. muscle), abnormalities in heart As for children, the new warnings
Dexedrine (dextroamphetamine rhythms and any other problems that suggest that, before a patient of any
sulphate) is an amphetamine that predispose them to be vulnerable to age is given a stimulant-type drug, he
works by mimicking the effects of the stimulation of the central nervous should undergo a thorough physical
hormone adrenaline (epinephrine), system. exam to determine if they have cardiac
which triggers the bodys classic fight- Sudden death, stroke and heart disease. The same advice should apply
or-flight responses. attack have all been reported in adults to anyone developing chest pain or
The medical profession maintains
that ADHD results from a genetically
based abnormality in glucose levels and Psycho-cocktails
neurotransmitters in the brain. The
prevailing view is that drugs like the
amphetamines, which speed up bodily When children dont immediately respond with one of the old standbys,
processes in adults, have a paradoxical todays doctors tend to prescribe a cocktail of psychoactive drugs.
effect on children, calming them down These back-up drugs can even include antidepressants such as
and somehow sorting out the desipramine (a tricyclic drug) or, inexplicably, high-blood-pressure drugs such
biochemical imbalance. as clonidine (an antiadrenergic).
But this latest warning suggests One American girl was given Ritalin for her ADHD, and Prozac to help
that the two drugs act as stimulants in manage her anxiety, hypersensitivity and fear of bugs. When her teacher
children as well as in adults, raising complained that she was still disruptive in class, her doctor then handed her
blood pressure which, in turn, leads to Dexedrine. Her mother then noticed that her daughter was pulling out her
heart problems. eyebrows and eyelashes and, at that point, said Enough is enough and
The FDA still hasnt decided discontinued the Dexedrine.

WDDTY Dangerous drugs 29

Drugs for children

other problems suggestive of heart placebo over three years, found that
problems while taking the drugs. Not so calming: the treated children suffered a slowing
But that isnt the only area of
concern. The warning now states that
other side-effects of growth (2 cm less in height and
2.7 kg less in weight) over three years.
new psychotic or manic symptoms, Although this effect was temporary
including hallucinations, delusional u Restlessness in the short-term, its not known if it
thinking or mania in children and u Insomnia becomes permanent in chronic users.
adolescents, can also be caused by u Dyskinesis(involuntary Increasing susceptibility to seizures
stimulants at the prescribed dosages. movements such as spasm) and blurred vision are other reported
A meta-analysis of a number of u Tourette syndrome side-effects in the new warnings. GSK
short-term studies discovered that u Exacerbation of muscle and also notes: Long-term effects of
these kinds of symptoms occurred in phonic tics (any possible sound amphetamines in paediatric patients
one child out of 1000 (GSK prescribing or noise) have not been well established.
information, 2006). As many children are u Dysphoria (exaggerated feelings Lynne McTaggart
having to take the drugs for years, the of depression and discontent)
statistics could be far higher. u Euphoria (feelings of wellbeing
Other worrisome side-effects listed and elation)
in the new warnings include aggressive u Tremor
behaviour and hostility, and long-term u Diarrhoea or constipation
suppression of growth. Studies of u Anorexia/weight loss
children aged between seven and 10, u Impotence and changes in libido
randomized to receive Ritalin or a

30 WDDTY Dangerous drugs


Life after antibiotics

A new superbug could signal the end of antibioticsthe
drugs that ended research on phage therapy, an
approach that harnesses the power of viruses to kill
deadly bacteria
he test results from the getting that the bugs had finally won. bug into a superbug that is resistant

T hospitals laboratory were

worse than the doctors had
even dared to fear. They
signalled the end-days of a war that had
raged for more than 60 years between
They were looking at a doomsday
scenario of a world without
antibiotics, said Professor John Conly,
a specialist in infectious diseases,
months later. We are essentially back
to every antibiotic, including the last-
resort carbapenems. In August of last
year (2010), when the discovery was
made, 50 patients in hospitals in
London and Nottingham had been
antibioticsarguably the most to an era with no antibiotics (Bull World infected with NDM-1, most of whom
successful group of drugs ever Health Organ, 2010; 88: 8056). were health tourists who had gone to
developed, and which have made much The tests revealed that a gene India for cosmetic surgery.
of modern medicine possibleand the already known to doctors in Indiahad Since then, NDM has been
bugs. made its way to the West. NDM-1 (New discovered in New Delhis public water.
Specialists at the hospital in London Delhi metallo-beta-lactamase) is the Researchers have found 11 new species
knew from the results they were ultimate superbug. It transforms any of bacteria carrying the NDM-1 gene,

Alternatives to antibiotics
Phage therapy is not the only alternative to antibiotics. Many bugs, such as Chlamydia, E. coli, Salmonella and
others have been used for centuries in traditional medicine, Helicobactor pylori (Antibiotics, 1976; 3: 57788; Phytother Res,
although proof of their efficacy often rests on anecdotal 2003; 17: 21721).
stories and case studies. Good research is limited because u Honey. Manuka honey can clean chronically infected
funding usually comes from drug companies, which have no wounds and might help to reverse bacterial resistance to
commercial interest in discovering non-drug approaches. antibiotics. Honey interferes with the growth of three types
u Echinacea. Up until the late 1930s and the advent of of bacteria: Pseudomonas aeruginosa, streptococci and
antibiotics, Echinacea, a North American herbaceous MRSA, researchers from the University of Wales have
flowering plant of the daisy family, was a popular herbal discovered (Presented at the Society for General Microbiology
remedy for treating infections. In recent years, its primary Spring Conference, held in Harrogate, England, April 13, 2011).
use has been side-tracked by interest in its supposed u Garlic. Crushed garlic has been a recognized natural
abilities to fight the common cold, although some antibiotic for many centuries, and was recommended by
researchers are still interested in Echinaceas antibacterial Hippocrates as a disinfectant. Even garlic juice can slow
qualities. the growth of up to 20 types of bacteria. Yet, despite its
Using the commercially available product Echinaforce, age-old use, good research to prove its effectiveness is
researchers at the University of British Columbia in virtually non-existent.
Vancouver discovered that it could combat upper u Tea tree oil. This essential oil, made from the leaves of
respiratory infections, often the result of a viral Melaleuca alternifolia, has been used topically on the skin
complication. Echinacea purpurea also has an anti- to fight MRSA and other skin infections, such as acne,
inflammatory effect, they discovered (Phytomedicine, 2010; 17: athletes foot, nail fungus, wounds and infections. In
5638). laboratory tests, the oil killed the deadly MRSA bacteria,
Echinacea works in a similar way to antibiotics by although funds have never allowed a full clinical study to
attacking the bugs cell wall, researchers at Carleton be undertaken (Am J Infect Control, 2004; 32: 4028).
University in Ottawa have found (Med Mycol, 2010; 48: u Cranberry. These berriestaken as a juice, an extract,
94958). capsule or tabletare most often used against urinary
u Essential oils. Used as aromatherapy, essential oils have tract infections (UTIs). They have also been tested against
successfully combatted a host of bacteria, such as H. pylori infection, which can cause peptic ulcers.
staphylococci, streptococci and Proteus species. Within Although they are a proven UTI preventative, the evidence
three hours, 90 per cent of the bugs were killed in one test that they can also fight the infection is still inconclusive
that used clove, lavender, lemon, marjoram, mint, niaouli, (Cochrane Database Syst Rev, 2008; 1: CD001321).
pine, rosemary and thyme oils (Chir Dent Fr, 1976; 46: 53). u Others. Other natural antibiotics that have plenty of
u Goldenseal. This herb is a broad-spectrum natural anecdotal evidence, but precious little scientific support,
antibiotic that is especially effective when used together include St Johns wort, colostrum, selasih, liver herbs, wild
with Echinacea. On its own, it has proved to be a oregano, grapefruit seed extract, colloidal silver and
successful antidote against some of the more familiar liquorice root.

WDDTY Dangerous drugs 31


some of which can cause cholera and

dysentery, in the citys water supply. Probiotics and the good bacteria
Professor Tim Walsh, the lead
researcher from Cardiff Universitys
The human gut contains hundreds of different types of bacteria. Most of them
School of Medicine, fears that public
are good probiotics; they maintain the ecological balance that keeps us
water throughout India, Pakistan
healthy and wards off the bad bacteria. However, when the bad bacteria gain
and Bangladesh could be
the upper hand, we take a broad-spectrum antibiotic that kills the good along
contaminated with the super-bug.
with the bad.
Westerners who had not been in Indian
When that happens, the guts natural eco-system is disturbed, the defence
hospitals have already been infected,
system is impaired, and we are more likely to become a host for bad bacteria
he added (Lancet Infect Dis, 2011; 11:
and especially Clostridium difficile.
Probiotics are the best way to restore our natural barriers after a course of
Ironically, the NDM superbug may
antibiotics, researchers at the University of Paris-Sud in France have found. In
be the creation of the pharmaceutical
one study of 53 infants, 26 tested positive for C. difficile bacteria. Those who did
industry. Researchers have discovered
not have the bug had high levels of Bifidobacterium longum, a species of the
that Indias waterways are polluted by
good probiotic bacteria (J Clin Microbiol, 2010; 49: 85865).
pharmaceuticals, including antibiotics.
Many pharmaceuticals are processed in
India, where manufacturers can take Just as with Fleming and successfully countered dysentery and
advantage of lax environmental antibiotics, bacteriophages were gangrene.
controls to deposit their waste into the discovered by accident. In fact, two Even after the war, Russian
nearest river. meneach working independently scientists persisted with the therapy,
Researchers from the University of discovered them at around the same although the restrictions of the Cold
Gothenburg in Sweden, who made the time. War prevented any research findings
discovery, fear that the manufacture of One of them, George Eliava, head of from reaching the West.
pharmaceuticals could paradoxically the Central Bacteriology Laboratory in
spark a global epidemic of infectious the Georgian capital of Tbilisi, Phage one
diseases (PLoS ONE, 2011; 6: e17038) collected specimens of water from the Bacteriophages have many advantages
NDM is the inevitable end-point of citys Mtkvari river to study cholera over antibiotics. They are in limitless
an injudicious use of antibiotics that, bacteria. He left the slide under a supply, they attack only a specific
since the mid-1940s, have been microscope for three days and, when he bacterial species and do not have the
inappropriately prescribed, used on next looked, the bacteria had gone. same debilitating effects on the overall
crops, fed to live-stock, and washed There had been something else in the immune system that antibiotics can
away into our water-ways and back into water that was choleras natural enemy, have.
the public systems. he surmised, and that something was The one major disadvantage of the
bacterio-phages, as they had been therapy is that there is only one
The phage is set dubbed earlier by French-Canadian bacteriophage for each bug, so there
The discovery of antibiotics was scientist Flix dHerelle. has to be one Escherichia coli
accidental. While he was studying The two men collaborated and, from bacteriophage to nullify the E. coli bug.
influenza at Londons St Marys 1923, worked together at a new This presents two problems for the
Hospital Medical School in 1928, institute in Tbilisi, which was later doctor: he may not be able to treat the
biologist Alexander Fleming noticed on renamed in Eliavas honour. patient immediately, as he first has to
his return from a holiday that mould Within a few years, the scientists at be sure of what is causing the infection
had grown on a set of culture dishes the institute had created an and, second, there is no such
being used to develop the armamentarium of more than a dozen thing as a broad-spectrum
staphylococci germ. The mould had phages that could treat a range of bacteriophageone that will kill a
created a bacteria-free circle around bacterial infections. wide range of bugsas there is in
itself. Fleming experimented further Bacteriophages became part of antibiotics.
and named the active substance conventional medicine in the new However, the greatest advan-tage of
penicillin. However, it took another USSR. In the US, drugs giant Eli Lilly bacteriophages is their natural ability
17 years before penicillin went into took a keen interest in the therapy, to adapt as quickly as their preythe
mass production. and started its commercial bacteriawhereas an antibiotic
Despite its slow progress, Flemings development. However, the early represents a frozen moment of millions
accidental discovery halted research results were not convincing, and of years of evolution while the bacteria
into an equally promising antibacterial research and production stopped once continue to adapt, eventually creating
approach that was happening at the the first antibiotics were produced. an antibiotic-resistant superbug. As a
same time. Phage therapy harnesses However, in the USSR, phage result, there is no such thing as a
the natural power of a type of virus therapy continued, and bacterio- superbug that can beat its
called bacteriophages (which literally phages were regularly used to treat the bacteriophageor, at least, not for
translates to bacteria-eaters) to kill wounds of Russian soldiers fighting in longas the phage will adapt in order
bacteria. the Second World War. The therapy to continue having the upper hand.

32 WDDTY Dangerous drugs

The age of the superbug Antibiotics down on the farm
Superbugs began to appear within a
few years of the start of penicillins Even if we dont take antibiotics, we are still exposed to them whenever we eat
mass production. By 1947, four years meatespecially poultry.
after penicillin was launched, But theres an alternative for poultry breeders that American scientists have
researchers discovered the existence of been testing. A dietary yeast extract appears to be every bit as good as an
a form of Staphylococcus aureus that antibiotic for decreasing pathogens in organic turkey production, say
was resistant to methicillin, then the researchers working for the US Department of Agricultures Agricultural
most popular antibiotic in use. Today, Research Service (ARS).
these bacteria are better known by the The yeast extract works by boosting the immune system and so providing a
initials MRSA (methicillin-resistant natural defence against the bacteria that cause illness in the birds (Poult Sci, 2010;
Staphylococcus aureus), and they join 89: 44756).
a host of other antibiotic-resistant In a separate study, researchers from the University of Delaware say there is
superbugs that have become familiar growing evidence for several alternatives to antibiotics that poultry breeders
names, including E. coli, Clostridium could use. These include bacteriocinsnatural agents that
difficile and Salmonella. are lethal to bacteriaas well as antimicrobial peptidesa natural defence
Each year, antibiotic-resistant bugs, against some pathogensand bacteriophages (see main story) (Poult Sci, 2003;
such as MRSA, kill around 100,000 82: 6407).
patients in hospitals in America alone
(Clin Infect Dis, 2011; 52 [suppl 5]; doi:
10.1093/cid/cirl154). MRAB (multidrug- stop indiscriminate antibiotic use. It discovered that mincemeat sold in
resistant Acinetobacter baumannii) is had discovered that group A German shops was contaminated with
another common cause of infection in streptococci, a virulent infection, was vancomycin-resistant enterococci
hospitals. In one study of 164 infected becoming resistant to erythromycin, (Lancet, 1996; 347: 1047).
patients, 37 died, and 72 per cent of which is used as an alternative for Our waterways have also become a
the MRAB samples were resistant to people who are allergic to penicillin. breeding ground for superbugs, and
multiple drugs (BMC Infect Dis, 2010; 10: After the policy change, the level of they may already have entered our
196). strepto-coccal bugs fell from 16.5 per drinking water, one research team
In Sweden, the staphylococcal skin cent in 1992 to 8.6 per cent in 1996 (N fears.
bacteria S. epidermidis are widespread Engl J Med, 1997; 337: 4416). The UKs They took water samples from
in hospitals. They have the capacity to National Institute for Health and rivers, lakes and wells throughout
adapt to hospital environments, Clinical Excellence (NICE) issued its North America, Europe and East Asia,
accord-ing to a doctoral research paper own edict in 2008 in an attempt to and discovered significant traces of
by Micael Widerstrm at Umea reduce the 38 million prescriptions pharmaceutical drugs, including
University, Sweden (submitted in written for antibiotics every year in antibiotics. Industrial plants wash the
September, 2010). Great Britain. waste from the manufacture of
Another superbug, known as KPC pharmaceuticals into waterways, and
(Klebsiella pneumoniae carba- Eating and drinking antibiotics patients often flush prescription drugs
penemase), has been making its way In fact, even when we arent taking down the toilet. They are also used on
across the US since its discovery on the antibiotic drugs, were absorbing them farms for crop-growing to control
East Coast in 1999, and there have also through the environment and the food disease and these, too, can be washed
been outbreaks in Israel. According to we eat. Researchers have discovered into the nearest river. The researchers
a report from the Rush University that nearly half of the meat and poultry found three classes of antibiotics in the
Medical Center in Chicago, IL, in sold in stores is contaminated by water they analyzed that can create
October 2010, KPC causes pneumonia antibiotic-resistant staph infections. superbugs. Once in the waterways, they
and urinary tract infections. The bugs, which can cause life- can make their way into the public
The rise of the superbug has been threatening diseases such as supply and the water we drink, wash
caused by the widespread misuse of pneumonia and sepsis, are the result of and cook with, says lead researcher
antibiotics. Today, there are more than intensive-farming methods. The Sbastien Sauv, from the University of
150 different antimicrobial comp- research team bought 136 meat Montreal (Environ Health Perspect, 2009; 117:
ounds, and most of them are being samples from 26 stores in five US 67584).
prescribed inappro-priately. One study cities; of these samples, 47 per cent
estimates that 80 per cent of antibiotic were contaminated with S. aureus Turning the phage
prescriptions are written for ailments bacteria. Although the bacteria are Despite the rise of the superbug,
that the drugs cannot treat, such as usually killed in the cooking process, research into phage therapy began to
viral infections (J Antimicrob Chemother, the researchers fear that some of the dwindle in the USSR and, by the mid-
2007; 60 [suppl 1]: i3i90). bugs may be left on kitchen surfaces 1970s, the Eliava Institute had virtually
Finlands health authority during preparation (Clin Infect Dis, 2011; closed its doors. Without electricity,
was one of the first to act when, 20 52: 122730). This is not a even the phage samples being stored in
years ago, it issued new guidelines to new development. In 1996, researchers the refrigerators would have been lost

WDDTY Dangerous drugs 33


had the researchers not taken them

home. In 1993, the electricity was Diseases caused by antibiotics
switched off for good, and the Institute
was closed. Antibiotics dont only help to create the superbugs. They can also cause
Today, phage therapy is active only asthma, leave us open to serious bacterial attack, cause birth defects and send
in Georgia and, to a lesser extent, in us to the hospital emergency room with hypotension (abnormally low blood
Poland. pressure).
However, in the West, it was u Asthma. Babies who are given antibiotics are 50 per cent more likely to
beginning to dawn on the researchers develop asthma when they are small children. In a study of around 1400
who were studying the rise of children with asthma, around one-third had been given antibiotics by the
superbugs that antibiotics carry the time they were six years old. The antibiotics interfere with the good bacteria
signature of their own eventual in the gut, which prevents the immune system from maturing, say
ineffectiveness. They started to take a researchers from the Norwegian University of Science and Technology (Am J
fresh look at phage therapy. In 1994, Epidemiol, 2010; 173: 3108).
researchers used phages to help u Birth defects. Antibioticsand the sulphonamides and nitrofurantoins in
improve the success of skin grafts in particularcan cause birth defects if taken when a woman is pregnant.
laboratory mice by reducing Although defects were also seen in women who had taken penicillin, the risk
the underlying Pseudomonas was less evident (Arch Pediatr Adolesc Med, 2009; 163: 97885).
aeruginosa infection (Burns, 1994; 20: u Immunity. Our natural immunity can be impaired for up to two years after
20911). taking antibiotics, leaving us more open to serious infection. A study by the
Phages for killing Listeria, the food- Swedish Institute for Infectious Disease Control revealed that the impact of
poisoning bacteria, have started to be antibiotics is far greater
used tentatively in the West (Lancet, than the common belief that impairment lasts for only a month or so
2000; 356: 1418). (Microbiology, 2010; 156: 321623).
A clinical trial of phage therapy for u Hypotension. Antibiotics can cause life-threatening shock and hypotension
otitis, a bacteria-caused middle-ear (too-low blood pressure) if they are taken with common blood-pressure
infection, has been underway at medications. The macrolide antibioticswhich include erythromycin,
Londons Royal National Throat, Nose clarithromycin and azithromycincan increase the risk of sudden
and Ear Hospital (Clin Otolaryngol, 2009; 34: hypotension sixfold if taken with a calcium-channel blocker drug (CMAJ, 2011;
34957), while a research team at the doi: 10.1503/cmaj.100702).
University of Minnesota in Minneapolis
tested a cocktail of phages against
various antibiotic-resistant bugs such News_PR062308.htm). has adapted in order to outwit the
as MRSA and E. coli in venous leg Intralytixwhich recruited several antibiotic.
ulcers (J Wound Care, 2009; 18: 2378, researchers from the old Eliava Understanding this, antibiotics
2403). Instituteis hoping that the use of should have been treated as a precious
ListShield will demonstrate the safety resource and used sparingly. Instead,
Animals first of phage therapy and will eventually we have killed the goose that laid the
Acceptance of phage therapy herald in a way of combatting killer golden egg.
may be slow in the West, but it appears bugs in the way that Nature intended. Fortunately, there is another goose
to be happening faster for agricultural that can come to our rescueMother
and livestock purposes. In 2006, the The new age of the phage Nature herself.
European Union banned the use of Antibiotics have been medicines Bacteriophages are Natures own
antibiotics for non-medical purposes in greatest success story, and have answer to bugs, and there
animals and livestock, while several doubtlessly saved millions of lives. They is one bacteriophage for every bug.
manufacturers have been phasing out have been the doctors most powerful They are found in limitless supplyjust
growth-promoting antibiotics. ally, and have granted him miraculous put a bucket into any river and you will
A number of companies are healing powersand, as a result, have fish out trillions of themand they
currently working on the commercial been absurdly overprescribed over adapt along with the bug.
mass production of phages for the years. Whats needed is just for the West to
livestock. One, Intralytix, has been While the antibiotic has been a realize that the end-days of antibiotics
granted a US license to develop moment of millions of years of are with us now, and to work with the
a phage to combat Listeria evolution frozen into a chemical Russians on the research they carried
monocytogenes in poultry. The licence, formula, its preythe bughas out right up until the 1970s, and begin
granted in 2006, is for a product called continued to adapt in order to survive. funding the age of the bacteriophage.
ListShield ( The superbug is just thata bug that Bryan Hubbard

34 WDDTY Dangerous drugs

Antibiotics: definitely not kids stuff
Routinely given as preventative drugs to mothers-to-be
and infants, antibiotics are far more dangerous than we
could have previously imagined, as new research
ntibiotics are routinely given effective than a placebo in preventing

A to pregnant women and

young children. In the US,
30 million prescriptions are
written each year for childhood ear
infections alone, and there are more
infection, not even in cases of a
ruptured membrane.
This suggests, say the researchers,
that only those women who are very
likely to develop infection due to
because of indiscriminate antibiotic
use. It was reckoned that two-thirds of
cases of deafness in children were
being caused by the overprescribing of
antibiotics such as streptomycin and
than 60 different antibiotics that can membrane rupture or to suffer other gentamicin (BMJ, 1996; 313: 648).
now be given to infants. injuries that could lead to infection The lessons to be learned seem
However, while these drugs have should be given antibiotics in future. clear, says Alison Russell, of Warwick
saved lives, they are also known to be Certainly, their routine use should Medical School in the UK. Contrary
among the most dangerous groups of be stopped (Lancet, 2008; Sep 18; Epub to the popular opinion that anti-
drugs around. ahead of print). biotics dont do any harm so we might
One study found that antibiotics Nevertheless, and despite these as well give them, antibiotics are not
can cause long-term health problems findings, the Royal College of Obstet- risk-free.
in children whose mothers took these ricians and Gynaecologists, which sets
drugs during pregnancy. Antibiotics the best practice guidelines in the Adverse events are common
are regularly given in pregnancy to UK, says it will not be altering its Dr Russells opinion has been
reduce the possibility of premature current recommendations. In 2001, supported by the fact that antibiotics
labour and to guard against infection. the RCOG changed its guidelines are responsible for 20 per cent of
Yet, this routine procedure has for the management of preterm all drug-related visits to Accident &
genuine health risks for the unborn membrane rupture to exclude co- Emergency departments. It appears
child. Researchers at the University of amoxiclav (amoxicillin and clavulanic that, over a two-year period, 142,000
Leicester in the UK found that the acid) from the treatment protocol. Americans reacted so badly to an
antibiotic erythromycin dramatically antibiotic that they had to be admit-
increased the risk of having a child Drugs for newborns ted to hospital. Indeed, antibiotics
who would develop visual or hearing Antibiotics are just as dangerous for were as dangerous as drugs such as
impairment, or even cerebral palsy, by newborns. One study has established warfarin, insulin and digoxin, all of
the age of seven. that children who are given an which have a known track record for
The team tracked 4221 women who antibiotic in their first 12 months of causing serious adverse reactions.
had taken either erythromycin or life are twice as likely to develop Nearly 80 per cent of the antibiotic
amoxicillintwo commonly used asthma by the time they are seven. patients who received hospital care
antibioticsor a placebo while preg- The risk is highest among children did so because of allergic reactions,
nant. Of these, 658 children whose who have undergone four courses of whereas the rest of the patients
mothers had taken an antibiotic had antibiotics and have taken broad- suffered from severe diarrhoea, head-
some kind of functional impairment. spectrum drugs for general just-in- ache or dizziness. Also, around 6 per
Their health problems included case healthcare. cent had to stay in hospital for at least
seizures, ADHD (attention-deficit/ Researchers in Canada made the one night (Clin Infect Dis, 2008; 47: 73543).
hyperactivity disorder), respiratory discovery when they reviewed the Yet, despite these dangers, doctors
conditions such as asthma, diabetes medical histories of 13,116 children. continue to give so many antibiotics
and bowel disorders. Those who were prescribed anti- to children that there are now
In general, the children of mothers biotics for anything other than a considerable rates of antibiotic
who had taken the drugs were nearly respiratory problem, thereby exclud- resistance, researchers at Oxford
twice as likely to develop cerebral ing those who had a preexisting University have found. In 119 children
palsy vs those whose mothers took a condition that might have led to with acute respiratory tract infection,
placebo. These children were also asthma, were twice as likely to develop 71 were given amoxicillin,
much more likely to have problems asthma as those given a placebo a moderate-spectrum penicillin. After
in learning to walk, other learning (Chest, 2007; 131: 17539). just two weeks, the number of these
difficulties and poor eyesight by the But the dangers of antibiotic use in treated children carrying antibiotic-
age of seven compared with those children have been known for years. A resistant bacteria had doubled
whose mothers had taken a placebo. study published as far back as 12 years compared with those only taking a
Worst of all, the researchers found ago found that children placebo (BMJ, 2007; 335: 429).
that the drugs had not been any more in Nigeria were losing their hearing Bryan Hubbard

WDDTY Dangerous drugs 35

Drug-induced disease

Medicine and the elderly:

age shall not weary
thembut drugs might
For the elderly, the cure is
very likely worse than the

oets may exhort us not to

P grow old, but they could have

added the rider that, when we
do, stay away from the doctor
for as long as possible. Growing
evidence suggests that aggressive
interventions by doctors are
accelerating the decline in the general
health and mental capacities of the
elderly, and may even be a direct
contributor to their death.
The over-65s take one-third of all
pharmaceuticals that are prescribed
by doctors every year, despite the fact
that they represent just 13 per cent of
the total population. On average, an while they are there. In addition, they invariably seen by a general practi-
elderly person is taking around six are also twice as likely as a younger tioner, whose almost instinctive
drugs at any given time (Johnston CB. patient to die within 30 days from tendency will be to start reaching for
UCSF Division of Geriatrics Primary Care Lecture such an attack. Researchers made the the prescription pad. Sadly, as discover-
Series May 2001. Geriatric Assessment in a Time discovery when they examined the ed by a doctoral thesis defended by
Dependent Practice: Practical Approaches for health records of 7054 patients who Sandra Pennbrant, at the Sahlgrenska
Primary Care Practitioners). were admitted to hospital as part of Academy in Sweden, elderly patients
Polypharmacywhen more than the US Veterans Health tend to become passive when faced by
one drug is prescribed at a timeis an Administration between 2003 and the doctor and feel intimidated by the
even bigger problem in hospitals and 2004. Of those patients, 792or 11.2 practitioners power and, so, fail to
care homes, where the average patient per centsuffered a heart attack participate in the consultation by
is given at least seven different drugs while under hospital care (Arch Intern almost never challenging the decision
every day. In addition, powerful Med, 2006; 166: 14106). to start taking a drug or even asking
dementia drugs are being prescribed any questions (
for most patients as a chemical cosh Tick-box medicine handle/2077/21198).
to keep them quiet, evidently mainly Most patients are over 65 and, yet, Doctors routinely hand out
for the convenience of the medical they rarely see a doctor who prescription drugs simply because the
staff. An official UK government specializes in geriatric medicine. This patient is old, not because he or she
review has revealed that the drugs are might be because, in almost every needs them, says Michael Oliver, an
being inappropriately prescribed in country except the UK, there is a emeritus professor of cardiology at
around 80 per cent of cases. In the UK serious shortage of geriatricians. In Edinburgh University. This tick-box
alone, this works out to around Canada, for example, there are fewer medicine, as he calls it, means that
150,000 people who are being given than 200 qualified geriatricians elderly people are not only taking
anti-psychotic drugs just to keep them serving the entire country. In an drugs they dont need, but they are also
pacified. Worse, the drugs are directly attempt to attract more medical being exposed to side-effects that can
responsible for about 1800 deaths graduates into geriatric medicine, Dr seriously endanger their health.
every year ( Laura Diachum, at the University of Nowadays, few elderly people are
hi/8356423.stm). Western Ontario, has gone as far as to allowed to enjoy being healthy, he says
This may perhaps explain why 11 describe the speciality as totally (BMJ, 2009; 338: b873).
per cent of elderly patients, admitted sexy (J Am Geriatr Soc, 2006; 54: 145362). One example of this so-called tick-
to hospital for other medical As a result of the lack of geriatric box medicine is bringing down levels
conditions, will suffer a heart attack specialists, an elderly patient is of blood cholesterol, especially in the

36 WDDTY Dangerous drugs

elderly. But this is, in fact, a failure to from the Yale University School of In another study, researchers found
understand the changing metabolism Medicine. There, the researchers found that 20 drugs had been identified as
of older patients, who appear to need that, while there was a marginal benefit being too dangerous for use by the
higher levels of cholesterol for their from the drugs in reducing heart elderly and, yet, most of these patients
general wellbeing and, especially, to fatalities, they also found that the (79.6 per cent) were being prescribed
support mental acuity. One study that patients were dying of other causes as one of these drugs and 20.4 per cent
involved 3572 men, aged 7193 years, a result of taking the drugs (JAMA, 1994; were taking two or more, including the
discovered that those who had the 272: 133540). beta-blocker propranolol, the anti-
lowest cholesterol levelsfrom 2.09 Worse, most general practitioners hypertensive agents methyldopa and
to 4.32 mmol/L (80.0 to 167.0 are unaware of the dangers of the reserpine, the painkiller dextropropoxy-
mg/dL)were up to 40 per cent drugs they are prescribing to their phene and the anticoagulant dipyrid-
more likely to die than those whose elderly patients, despite the frequent amole (JAMA, 1994; 272: 2926).
cholesterol levels were higher. Indeed, drug alerts and warnings they are sent Many elderly people regularly take a
this study, which monitored the by drug-monitoring agencies. common NSAID (non-steroidal anti-
health of the partici-pants for 20 In fact, researchers have discovered inflammatory drug) such as aspirin and
years, questioned whether there was that around one in five elderly patients ibuprofen to help ease their aches and
any scientific justification for is being given drugs that are dangerous, pains. Yet, according to a survey of 4099
lowering cholesterol to very low and could be the cause of debilitating people aged 70 years and over, these
concentrations (below 4.65 mmol/L side-effects. In a study of 760,000 drugs increase the risk of kidney
[179.8 mg/dL]) in elderly people elderly people taking a prescription dysfunction. Those who took an NSAID
(Lancet, 2001; 358: 3515). drug, it was revealed that 21 per cent at least once a day had the highest
Not only may higher cholesterol were taking one or more drugs that levels of blood urea nitrogen and serum
levels be health-giving in the elderly, were on the Beers list, a compilation of creatinine, both of which are markers of
but the cholesterol-lowering drugs all the prescription drugs that geriatric kidney problems (J Am Geriatr Soc, 1999; 47:
themselves may also be doing more patients, in particular, should avoid 50711).
harm than good, according to a study (Arch Intern Med, 2004; 164: 16215). Prescribed drugs may also be

Living a long and healthy life

Aside from avoiding drugs and medicine, there are three
keys to a healthy life into old age: diet; exercise; and an such as heart disease and arthritis can see improvement.
active social life. In heart patients aged 50 years and over, moderate
exercise that leaves you a little out of breath increased life
u Diet. Vitamin Efound in nuts, seeds, and corn and olive expectancy by 3.7 years in men and 3.5 years in women
oilis arguably the single most important nutrient in (Arch Intern Med, 2005; 165: 235560). Older people with
determining whether or not we will live a long and healthy osteoarthritis of the knee also noticed improvements in
life. In a study of 698 men and women, aged over 65 and their knee pain and mobility after 18 months of brisk
living in Tuscany, Italy, those who had low levels of the walking for 40 minutes, three times a week (JAMA, 1997;
vitamin in their circulation suffered a decline in their 277: 2531). Overall, older people who take regular exercise
physical capacity over a three-year period compared with have stronger hearts, better circulation, stronger bones,
those who had higher levels of the vitamin. This was also better balance, less pain, better sleep quality, sharper
the only vitamin that had a direct impact on the physical minds and a lower risk of developing most cancers (Am
wellbeing of the study participants. Their levels of folate, Fam Physician, 2002; 65: 41926).
vitamin D, iron and B vitamins apparently made no u Social networks. An active social life, including volunteer
difference to the physical decline. The researchers believe work, attending sports and social events, and visiting
that vitamin E, which is an antioxidant, prevents damage friends and relatives, is as important as exercise for
to DNA, muscles and neurons (JAMA, 2008; 299: 30815). helping older people to maintain good health. In a US
The Mediterranean diet, primarily consisting of fresh study of 906 retired people, it was found that physical
fruit, vegetables and olive oil, has been proven in decline was up to a third more rapid in those who were
countless studies to help maintain health into older age. socially inactive, even when they took regular exercise
One study, involving 1393 participants, discovered that (Arch Intern Med, 2009; 169: 113946). Curiosity and
the diet protects against cognitive decline as we age. maintaining an interest in the world also play important
Those who stayed close to the diet nearly halved their roles in determining how longand how wellwe live.
chances of developing mild cognitive impairment One study of 1118 men, with an average age of 70 years,
compared with those who ate low amounts of fruits and found that having this attitude in life was the single most
vegetables (Arch Neurol, 2009; 65: 21625). important factor in determining longevity.
u Exercise. Even moderate exercise, such as a brisk walk In ancillary analyses in 1035 older women (mean age:
every day, can help to keep you healthy into older age, 69 years), curiosity appeared to be equally important in
and even elderly patients who already have conditions women as well (Psychol Aging, 1996; 11: 44953).

WDDTY Dangerous drugs 37

Drug-induced disease

therapy (Age Ageing, 1996; 25: 2738).

Staying sharp In a separate small US study a
year later, the geriatric researchers
Mental decline isnt an unavoidable consequence of ageing. Theres lots we in Durham, NC, found that benzo-
can do to stay sharp right up to the end. diazepines acted directly on the
People who exercise at least once a week, dont smoke and maintain an central nervous system, and affect
active social life are more likely to retain their cognitive abilities throughout their neuromuscular processing and
70s and 80s, according to a study of 2500 participants aged 7079. However, balance control, thereby causing
an eight-year follow-up showed major cognitive decline in 16 per cent of this falls, disorientation and slower
population, whereas 53 per cent displayed normal, age-related decline. Yet, the responses in the elderly (J Am Geriatr
research team saw a unique profile of activity and social engagement that Soc, 1997; 45: 43540).
appeared to have protective effects in around 30 per cent of participants who Powerful antidepressants of the
displayed no cognitive decline whatsoever. A good education, not smoking class known as SSRIs (selective
and a good level of literacy were found to be important factors, and those who serotonin-reuptake inhibitors) as
carried out volunteer work and were not living on their own also appeared to well as the older tricyclic drugs, can
be less likely to suffer from cognitive decline (Neurology, 2009; 72: 202935). also significantly increase the risk of
Maintaining an interest in intellectual pursuits, such as reading and doing falls in the elderly (N Engl J Med, 1998;
crossword puzzles, can also help to ward off dementiaand the more you do, 339: 87582). As a consequence,
the better. The study participants who engaged in 11 intellectual activities a elderly people taking an SSRI are 2.4
week, such as reading every day and doing the crosswords four times a week, times more likely to suffer hip
delayed the onset of dementia by 1.29 years compared with those who read or fractures compared with those not
did the crosswords taking these drugs, researchers from
the University of Toronto, Ontario,
responsible for dry eyes and dry mouth, and Cassell, 1965). Every health concern have found. However, the earlier
assumed to be a natural consequence in the elderly could be traced back to types of antidepressant are not much
of growing old. However, common pain- one of those four conditions, he said. safer for elderly patients. In this
killers such as aspirin could be respon- However, neither Isaacs nor the other study, which involved 8239 patients,
sible, according to a study of 2481 pioneers of geriatric medicine could aged 66 years and over, who had
patients aged 6584 years. Antidepress- have foreseen that, in many older been treated in hospital for hip
ants and antipsychotics may also be the patients, these giants would be caused fractures, it was found that those
cause of similar side-effects (Arch Intern by the very medicines that were taking a tricyclic antidepressant
Med, 1999; 159: 135963). supposed to help them, and not by the such as desipramine or nortriptyline
Whats more, doctors are more than ageing process itself. were 2.2 times more likely to suffer
ready to prescribe off-labelhanding u Immobility and instability. Around from hip fractures as a result of falls
out drugs for health problems for which 30 per cent of all over-65s fall each (Lancet, 1998; 351: 13037).
they have been neither tested nor year, and this proportion rises to half Insulin can also cause falls, and is
licensed to treat. The problem has of all those in hospital or in nursing among the three drugs that are also
become so prevalent, and dangerous, care, where multiple drugs are an most likely to cause an adverse
that Americas drugs watchdog, the essential part of their daily regimen. reaction in the elderly; the other two
Food and Drug Administration (FDA), Also, 25 per cent of these patients are warfarin, a blood thinner, and
has warned doctors to stop using die within six months of falling. digoxin, a heart drug. The three
atypical antipsychotic drugs to treat While there may be a number of drugs alone accounted for 59,108 of
general behavioural problems in elderly reasons why an elderly person falls, the 177,504 cases of adverse drug
patients. Indeed, agents such as olanza- prescription drugs are among the reactions reported by US emergency
pine, aripiprazole, risperidone and biggest causes, responsible for services in 20042005. Insulin can
quetiapine are so dangerous that they around 18 per cent of all cases cause sudden hypoglycaemia (low
double the risk of deathand they are (Johnston CB. UCSF Division of Geriatrics blood sugar), which may result in a
supposed to be prescribed only to those Primary Care Lecture Series May 2001. seizures or unconsciousness (Ann
with schizophrenia ( Geriatric Assessment in a Time Dependent Intern Med, 2007; 147: 75565).
advisory/antipsychotics.htm). Practice: Practical Approaches for Primary In fact, most prescription and
Care Practitioners). over-the-counter drugs appear to
The four giants Tranquillizers and sedatives, such increase the risk of falling. In a meta-
In 1965, when geriatric medicine was as benzodiazepine, can increase the analysis of studies published from
still in its infancy, Bernard Isaacs, a risk of a fall in an elderly patient by 1996 to 2007, involving more than
professor of geriatric medicine at nearly threefold. Flurazepam and 79,000 participants, aged over 60,
Birmingham University in the UK, said triazolam (both of which are benzo- who were taking some sort of
the elderly were faced with four giants diazepines) are the most dangerous, pharmaceutical, it was found that
that would determine their health: according to Canadian researchers, many drugs significantly raised
immobility; instability; incontinence; and the elderly patient was most the risk of falls. The biggest culprits
and impaired intellect (Isaacs B. An likely to suffer a fall within the first included sedatives, SSRIs, antihyper-
Introduction to Geriatrics. London: Ballire, Tindall two weeks of starting such drug tensives, diuretics, beta-blockers,

38 WDDTY Dangerous drugs

and even NSAID painkillers such as among the elderlyand often Neurology 60th Annual Meeting, Chicago, IL,
aspirin and ibuprofen. unnecessarily so, as one study has Abstract S51.001, 17 April 2008).
Elderly people may be more identified (BMJ, 1994; 308: 5113). Indeed, it appears that almost
sensitive to drugs effects and less Alpha-adrenergic blockers, which every commonly prescribed or over-
effective at metabolizing medica- include drugs for hypertension (high the-counter drug can produce
tions, leading to adverse events blood pressure) such as doxazosin symptoms that resemble dementia
which, in turn, lead to falls, said (Cardura), prazosin (Minipress) and in the elderly. A pair of researchers
researcher Carlo Marra, at the terazosin (Hytrin), can also cause from the Medical University of South
University of British Columbia in incontinence (Drug Saf, 1994; 11: 1220), Carolina have reported that many
Vancouver, Canada (Arch Intern Med, as can the angiotensin-converting drugs cause side-effects that include
2009; 169: 195260). enzyme (ACE) inhibitors such as confusion and memory loss, two
u Incontinence. This is often viewed as benazepril (Merck Manuals; www.merck. signs of cognitive impairment. In
an unfortunate consequence of com/mmhe/sec11/ch147/ch147a.html). addition, the problem can be
ageing, but this is not so. The US u Impaired intellect. Around 22 per magnified when the patient is taking
Agency for Health Care Policy and cent of those aged 71 years and over more than one drug at the same
Research reports that eight out of 10 have some degree of cognitive time (J R Soc Med, 2000; 93: 45762).
cases of incontinence can b either impairment, which is often seen as
resolved or greatly improved by a forerunner of dementia and Polypharmacy
medical interventions (Agency for Alzheimers disease (Ann Intern Med, Its evident that the dangers to the
Health Care Policy and Research. Overview: 2008; 148: 42734). However, research- elderly of taking any one drug are bad
Urinary Incontinence in Adults, Clinical ers at the Mayo Clinic reckon that enough, but its almost impossible to
Practice Guideline Update. Rockville, MD. this figure could be lower, with only measure the negative impact of taking
March 1996; 12 per cent of individuals aged many drugs at the same time, as most
htm). The one exception is age- between 70 and 89 years displaying elderly patients are doing.
related prostate enlargement, which such symptoms, according to a study Even young Hollywood celebrities,
can cause urinary incontinence. funded by the National Institute on such as Heath Ledger and Brittany
In fact, incontinence can arise Aging ( Murphy, may have died as a result of
for many reasons and in people of 3306.html). taking several pharmaceuticals at the
all ages, although one in 10 of those The Mayo researchers define same time.
aged over 65, and three in 10 aged cognitive impairment as having As Dr Bruce Goldberger, a professor
over 80, have some loss of bladder problems with remembering words, of toxicology at the University of
control, and half of all elderly or placing things in time and space, Floridas College of Medicine, said of
patients in nursing homes have or finding it more difficult to make the latters death, Mixing a number of
incontinence. Many prescription decisions, or suffering from short- these drugs could have resulted in her
drugs cause temporary incontin- term memory loss. The problem death.
ence and, as the elderly take one- doubles in those aged between 80 Every drug is tested for its safety and
third of all drugs prescribed, its not and 89, and it also appears to affect efficacy on its own, but no one is testing
unreasonable to conclude that they more people who have received only the lethal cocktails that can result from
are a primary cause of the condi- basic levels of education. taking several powerful chemical
tion in the over-65s. Anticholinergic However, although ageing is a compounds in combination.
agents, which block the passage of genuine factor in cognitive decline, Nevertheless, what is clear, as
neural impulses, include drugs such pharmaceuticals also play a role in pharmacologists at the University of
as antihistamines, antidepressants, accelerating the problem. Scientists Wales College of Medicine, Cardiff, have
opiates, antispasmodics and Parkin- from the University of Florida have pointed out, is that drugsand
sons drugs, and can all lead to demonstrated that any drug that has especially polypharmacymay be
incontinence (Cochrane Database Syst anticholinergic (nerve-blocking) responsible for many of the common
Rev, 2006; 4: CD003781), as can heart qualities can speed cognitive decline health problems seen among the
drugs such as the calcium-channel in the elderly patient. Although this elderly, such as confusion, weakness,
blockers. includes drugs known to have incontinence, depression and falls, all
Diuretics, or water pills, increase anticholinergic actions, such as of which have been blamed on growing
the bodys loss of fluid by promoting those used to treat an overactive old (Drugs Aging, 1998; 12: 48594).
the production of urine and, as a bladder, many other drugs have Without drugs and medicine,
result, can frequently cause acute similar effects, but have not been perhaps getting older wouldnt be such
incontinence. They are among the listed as such in the literature an unhealthy rite of passage.
most regularly prescribed drugs (Presentation at the American Academy of Bryan Hubbard

WDDTY Dangerous drugs 39

Drug-induced disease

The damaged brain: how drugs

cause dementia
New evidence shows that all forms of dementia
may largely be caused by most of the drugs we
take as we get older
e may be living longer elderly. Even though they represent

W and better than ever but,

by the time we reach our
golden years,
chances of us having any awareness
of it are rapidly fading. Dementia of
only one-seventh of the population,
the over-65s take one-third of all
prescription drugsand usually a
cocktail of them. The average senior
is taking six drugs at a time, many of
all varieties, including Alzheimers which affect the brain.
disease, is now epidemic, Evidence is emerging that a large
approaching an incidence similar to coterie of drugs given for other
that of the major killers: for instance, conditions, such as high cholesterol,
seven million Americans aged over depression, inflammation, insomnia,
65 are currently diagnosed with anxiety, heart disease and arthritis patients have movement disorders
dementia compared with 10 million in short, most of the drugs given to much like those seen in Parkin-
of all ages with cancer. us as we grow oldercan all bring on sons disease, with abnormal
Furthermore, the incidence rates dementia. deposits of Lewy body proteins,
of dementia are sharply on the Many of these drugs cause actual named after the German neurol-
increase. Predictions suggest that damage to the structure of the brain, ogist who first observed them,
the disorder will increase fourfold including shrinking brain volume and throughout the neurons of the
among the elderly within the next 40 destroying the crucial fatty struct- brain;
years, and escalate across all age ures of brain cells, thus leading to u vascular dementia, where the
groups. the abnormal accumulation of tissue brains blood supply has become
Nevertheless, the raw statistics fail in vital brain structures. cut off or interrupted, usually as a
to reveal the most insidious aspect of Given the fact that some 90 per result of large or small strokes,
the diseasenamely, that the cent of Americans from their mid-50s causing the death of neurons;
chances that any one of us will suffer onwards are taking at least one drug u frontotemporal dementia, usually
from dementia sharply increases with regularly and nearly one-third are diagnosed in patients aged under
every decade. According to one team taking five or more drugs, it may well 65, where the frontal or temporal
of researchers, who tracked the beas American psychiatrist Grace lobes (including the hippocam-
incidence of the disorder over time, E. Jackson claims in her brilliant and pus) of the brain shrink; and
after the age of 60, your risk of damning self-published studythat u Alzheimers disease.
developing dementia doubles every dementia is, in many cases, a drug- According to Jackson, Alzheimers
five years. This means that, by the induced disease (Jackson GE. Drug- victims all share three specific
time you reach your mid-80s, you Induced Dementia. AuthorHouse, 2009). Of abnormalities:
face a one-in-four risk of having the 36 million Americans who now u senile plaques, abnormal clumps
dementia and, by the time you reach take statins, for instance, an of amyloid and other sorts of
90, the odds increase to one chance estimated 162,000 people could be proteins that form outside of cells
in three (Alzheimer Dis Assoc Dis, 2003; 17: severely cognitively impaired because in the gray matter of the brain;
637). of these drugs in the US alone. u neurofibrillary tangles, abnormal,
One reason for the prevalence is twisted bundles of fibres within
simply due to the ambiguous nature The chicken or egg dilemma brain neurons mostly made up of
of the term. Virtually every form of Although used as an all-purpose tau proteins that impair the
cognitive decline is now classified as catch phrase, dementia could be formation of tubulin, a protein
dementia, including memory loss, defined as any condition in which necessary for healthy connective
and impairment in planning, judg- there is an observable abnormality nerve tissue, the result of which is
ment, reasoning and ordinary involving neurons or glial cells. On that messages in the brain arent
thought processes. the basis of such a description, it transmitted properly; and
However, modern medicine must could be said that there are four u granulovacuolar degeneration
take the greatest blame for the types of true dementia: (GVD), where neurons in the brain
mental decline seen among the u Lewy body dementia, in which have abnormal holes (vacuoles),

40 WDDTY Dangerous drugs

each of which contains a small,
dense protein. Why the brain needs fats
The problem is that researchers
cannot agree on whether these
characteristic findings are the cause Although medicine used to believe that the master conductor of brain
or the effect of an abnormal process activity was the neurons, or nerve cells, that create and release
in the body. The evidence from neurotransmitters and electrical signals, this view has been revised by a
studies of the effects of aluminium more holistic view of the brain. This concept appreciates that the brain
and mercury on the brain suggest works in its entirety through a web of activity between neurons and four
that they are the result of toxicity varieties of glial cells. Glial cells, which surround the neurons, keep them
rather than being a true cause of in place, provide them with nutrients, and destroy and mop up pathogens.
dementia. In test-tube studies using They also insulate one neuron from another and modulate the transmission
human brain cells, for instance, of signals. One major function of glial cells is to form myelinthe insulating
minute doses of mercury produced sheath that covers every tentacle of a nerve cellwhich is largely made up
changes identical to those seen in of lipid (fatty) tissue.
Alzheimers disease (J Neurochem, 2000; Yeon-Kyun Shin, a professor of biophysics at Iowa State University,
74: 2316). recently went on record to say that high cholesterol is vital for good brain
In other, animal studies, professor function, and a lack of cholesterol impairs the brains thinking ability and
of medical biochemistry Boyd Haley memory.
and colleagues at the University of If you deprive the brain of cholesterol, then you directly affect the
Kentucky fed rats aluminium, but machinery that triggers the release of neurotransmitters. Neurotransmitters
observed no changes in tubulin affect the data-processing and memory functions; in other words, how
levels, whereas mercury-fed rats smart you are and how well you remember things, he said (Proc Natl Acad
displayed diminished tubulin levels Sci USA, 2009; 106: 51416).
similar to those seen in typical
Alzheimers patients. Furthermore, The white matter is the part of the with those for patients who were not
some researchers suggest that the brain that contains bundles of nerve using any such drugs.
vacuoles seen in GVD are filled with fibres covered with myelin, a white They found similar incidences
toxic materials, such as aluminium, fatty substance that forms an insu- between the two groups of virtually
which the neuron has fenced in to lating sheath around each fibre. It is every condition looked atdiabetes,
keep the rest of the brain safe (Am J through these neural bundles that stroke, heart attacks, hypertension
Pathol, 1999; 155: 116372). messages are passed between save one. Those taking the anti-
Research at the University of different areas of gray matter, which depressant drugs experienced more
Pittsburgh has discovered that a fat- is made up of unmyelinated nerve bright spots in the white matter on
binding agent known as apolipo- cells, within the nervous system. MRI. This sort of appearance on a
protein D (or apoD in medico-speak) This means that the white matter scan is thought to indicate damage
is present in the brain plaques seen is rather like a telephone network, to blood vessels, impaired blood flow,
in patients with Alzheimers disease. responsible for the rapid transmis- demyelination (degeneration of the
However, apoD is also found in sion of nerve impulses and cell-to-cell myelin sheath of nerve cells),
other kinds of pathology, and many communication. disintegration of the bloodbrain
animal and human studies have One natural aspect of ageing is barrier and even damage to the nerve
shown that antipsychotic drugs losing neural connections. Each of us cells in the gray matter of the brain
induce the production of apoD. begins adulthood with some 176,000 (Stroke, 2008; 39: 85762).
Furthermore, scientists have found km of white matter, but we all should Indeed, those taking the drugs
this type of lipoprotein in fat and expect to lose around 10 per cent of suffered a 36-per-cent incidence of
brain cells following injury, which these connections with every decade white-matter damage compared with
suggests that it plays a role in cell of life. 27 per cent in those who had been
renewal and repair. However, antidepressants clearly drug-free over the decade. In
Nevertheless, the evidence in hasten this process. In 2008, a US addition, all types of antidepressants
general suggests that toxicitya study carried out by Duke University be they old or newhastened the
form of insult to the brainrather Medical Center in Durham, NC, decline. Whats more, although the
than natural cellular degeneration is published the results of the 10-year worst offenders were the old-style
the cause of dementia. study, which examined the magnetic tricyclic antidepressants, adverse
resonance imaging (MRI) scans of effects were observed with all of the
Antidepressants more than 1800 patients performed newer types of drugs that inhibit the
There is no doubt that certain drugs over two periods of timefirst, from uptake of serotonin. Overall, 60 per
cause damage to the structure of the 1991 to 1994, and then, from 1997 cent of the patients who used either
brain, thereby impairing its function. to 1999. The authors compared the type of antidepressants showed
Among the chief offenders are findings for the 163 patients who increased damage to white matter
antidepressants, which appear to had begun taking antidepressants that was above the norm.
target the white matter of the brain. between the first and second scans Antidepressants also appear to

WDDTY Dangerous drugs 41

Drug-induced disease

shrink the hippocampus, part of the

limbic system of the brain that is The role of coenzyme Q10
involved in long-term memory,
spatial navigation, learning and
mood. There is solid scientific It is well known that patients taking statins lose coenzyme Q10 (CoQ10) in
evidence that patients who are a dose-related manner. The drugs block production of both cholesterol
chronic users of antidepressants, and CoQ10 by inhibiting the enzyme precursor of not only cholesterol, but
particularly SSRIs (selective seroto- also that of CoQ10.
nin reuptake inhibitors) such as CoQ10 participates in chemical reactions, particularly those that involve
Prozac (fluoxetine), have smaller cellular energy production, and helps to make cell membranes more resis-
hippocampal structures compared tant to oxygen damage. It is found abundantly in the heart mostly because
with controls. of the huge energy requirements of cardiac cells.
In one fascinating study, the In fact, studies have shown that a deficiency of CoQ10 is linked with
hippocampi of long-time depressed heart failure and impaired heart function. Of 15 published studies in the
patients who were taking long-term literature, nine have confirmed that statins can significantly lower CoQ10
medication were compared with levels (Arzneim Forsch, 1999; 49: 3249).
those of two other patient groups: Critics of statins believe that the widespread use of these drugs has
those whod just been diagnosed caused an increase in statin cardiomyopathy, where the heart loses its
with the illness and had not yet ability to pump blood or heart rhythm is disturbed, leading to irregular
begun taking any drugs; and a group heartbeats. Drug manufacturers tacitly acknowledge this effect by offering
of non-depressed controls. There several drug formulations that combine a statin with CoQ10.
was no difference in brain size But a less well-known problem with blocking CoQ10 is that it interferes
between the just-diagnosed depress- with cognitive performance, resulting in memory loss and muddled
ed patients and the controls, whereas thinking. In an elderly person, this sort of side-effect is almost invariably
the long-time medicated showed a passed off as age-related dementia, requiring yet another coterie of
hippocampus that was 12 per cent wonder drugs.
smaller, on average, than those of Other researchers have been discovering that statins also inhibit and
the others (Proc Natl Acad Sci USA, 2003; cause mutations in mitrochondria cells, the energy power packs of the
100: 138792). body. Scientists now suspect that an array of neurodegenerative diseases
The importance of this study is are due to mutated or altered mitochondria.
that it demonstrates that its the
drugs themselves, and not the this population study may have biosynthesis. Nevertheless, although
depression on its own, that causes underestimated the risk, as one-fifth the drugs lowered cholesterol in the
the brain to shrink. of those using antidepressants died brain, this had no alleviating effects
Autopsies of cavaders have also during the study follow-up period. on Alzheimers disease whatsoever
revealed brain damage in those (Alzheimer Dis Assoc Disord, 2010 May 13
whod been long-term users of anti- Statins doi: 10.1097/WAD.0b013e3181d61fea).
depressants. In one Dutch study, of Statins, those miracle cholesterol- In fact, the lack of effectiveness
patients whod been taking anti- lowering drugs, also appear to lead to of statins as a treatment for
depressants, 73 per cent showed progressive cognitive decline. This is Alzheimers disease was finally estab-
evidence of brain cell death particularly ironic, as medicine has lished last year, when two reviewers
(apoptosis) compared with 33 per been under the illusion that cutting independently analyzed two large-
cent in patients using long-term down on cholesterol in the elderly is scale randomized controlled trials,
steroids and 6 per cent of their desirable particularly for the brain involving a total of 26,340 patients as
matched controls (Am J Pathol, 2001; (see box, page 41) and, consequently, part of the HPS 2002 and PROSPER
158: 45368). that statins can keep Alzheimers at 2002 studies, and reached an agree-
In addition, epidemiological bay. ment after discussing their results.
studies have also shown a greater It is true that statins can cross Their conclusion was that statins
incidence of dementia among the bloodbrain barrier and alter given late in life to individuals at risk
populations using antidepressants. cholesterol metabolism in the brain, of vascular disease have no effect in
Researchers in Copenhagen carried but this has no bearing on preventing either Alzheimers
out a sweeping study, involving nearly Alzheimers disease. Earlier this year, disease or dementia (Cochrane Database
a third of the entire Danish popu- Harvard University researchers, in Syst Rev, 2009; 2: CD003160).
lation, focused on patients aged over conjunction with a number of other Indeed, far from helping memory
40 whod taken antidepressants, even centres in the US, Germany and and cognitive function, statins can
if just one single time. The risk of Spain, gave statins for 12 weeks to cause sudden and complete memory
developing dementia was two to five patients with mild Alzheimers loss.
times higher in those whod used disease or mild memory loss. This evidence emerged when flight
antidepressants compared with non- During the course of this study, surgeon Duane Graveline suffered
users (J Affect Disord, 2009: 117: 249). they found a modest but signifi- global amnesia when taking atorva-
However, Jackson believes that cant inhibition of brain cholesterol statin (Lipitor) for the first time.

42 WDDTY Dangerous drugs

When his family doctor Jay S. Cohen
took up his case with Pfizer, the Other drugs to avoid
drugs manufacturer, he was sent
clinical evidence gathered before the
drugs release showing that there Besides the agents already mentioned (see main story), there is mounting
were 4.5 cases of severe cognitive evidence that you should also avoid the following types of drugs.
disturbance out of every 100 patients u Stimulants, such as methylphenidate (Ritalin). A vast number of animal
given the drug. studies show that all amphetamines cause parts of the brain to shrink,
This included cases of impaired, trigger degeneration of dopamine cells in the brain and reduce the
worsening or general lapses of survival of neurons in the hippocampus, among many other effects
memory, general forgetfulness and (Jackson GE. Drug-Induced Dementia. AuthorHouse, 2009).
short-term memory loss. Pfizers own u Beta-blockers, calcium-channel blockers and ACE inhibitors, and
studies had also discovered instances other drugs that aggressively lower blood pressure. These antihyper-
in which patients had difficulty tensives can lower blood flow to the brain and produce all the hallmarks
concentrating, or suffered of Alzheimers disease (Drugs Aging, 1999; 15: 1528).
abnormally slow or difficulty in u Antiarrhythmic drugs, given to correct abnormal heart rhythms, can
thinking, slowed or decreased mental also cause dementia.
activity, impaired intellect or u Anticholinergic drugs, a giant category that includes drugs for gastro-
judgment and even irrational intestinal problems such as diverticulitis and ulcerative colitis,
thinking. respiratory ailments such as asthma and genitourinary disorders such
Graveline and Cohen then con- as cystitis or prostatitis, are associated with cognitive decline in the
ducted an online literature search of elderly (Presentation at the American Academy of Neurology 60th Anniversary
MedWatch, the US Food and Drug Annual Meeting in Chicago, IL, 17 April 2008).
Association (FDA) database of u Opioids, many of which can cause delirium (Drugs Aging, 1993; 3: 34957;
reported drug side-effects, for Postgrad Med J, 2004; 80: 38893).
reports of severe cognitive u Non-steroidal anti-inflammatory drugs (NSAIDs). Initially thought to
impairment or serious amnesia offer protection against Alzheimers, different types of these common
associated with Lipitor. They found painkillers can cause a variety of cognitive changes, ranging from
662 such reports, including 399 delirium (indomethacin and sulindac) to disturbances in memory and
cases of amnesia and 236 cases of concentration (naproxen and ibuprofen) (Drugs Aging, 1999; 15: 1528).
memory impairment. The u Levodopa. This antiparkinsonian medication causes cognitive
investigating pair also found that, symptoms in up to 60 per cent of users (Clin Geriatr Med, 1998; 14: 10127).
over time, the complaints had
become more frequent (Townsend Lett
Docs, 2009; 311: 6470). taking the drugs. Furthermore, all of introduced the next generation of
MedWatch, which is thought to be the four patients who started taking neurolepticswhich also includes
notified of only 2.5 to 5 per cent of the drugs again suffered a recurrence olanzapine (Zyprexa), quetiapine
all drug side-effects, therefore suffers of their memory problems. (Seroquel) and risperidone (Risper-
from vast underreporting, so the true As a further nail in the coffin, not dal)that were dubbed atypical
incidence of memory problems from one single experimental study could antipsychotics to distinguish them
statins is probably closer to 66,000 find any evidence to support any from their older and supposedly more
or more. In fact, Graveline and benefit with statins in delaying dangerous cousins. These drugs are
Cohen believe that virtually every cognitive decline (Pharmacotherapy, supposed to suppress the psychotic
patient taking the drug suffers from 2003; 23: 87180). and antisocial aspects of schizo-
cognitive damage in one form or phrenia without all the antipyramidal
another that may be too mild to be Antipsychotic agents effects (World J Biol Psychiatry, 2000; 1:
initially detected. This is perhaps Another major culprit causing 20414).
because all statins lower levels of dementia is that broad class of drugs However, this newer generation of
coenzyme Q10, known to be vital for called antipsychotics. The first so- drugs comes with its own laundry list
brain function (see box, page 42). called neuroleptic medications were of dangerous, even life-threatening,
Graveline and Cohens detective developed in the 1950s to relieve side-effects, including serious mental
work has also been vindicated by a patients suffering from hallucina- deterioration.
meta-analysis carried out by Duke tions, paranoid schizophrenia and There is no doubt that the so-
University in Durham, NC, which other psychoses. Unfortunately, called antipsychotic drugs can
uncovered 60 patients with memory these drugs brought with them cause or speed up the development of
loss attributable to statins. Half the unwanted extrapyramidal (brain dementia (J Neurol Neurosurg Psychiatry,
patients had noticed cognitive motor system) side-effects such as 2007; 78: 2339). This is ironic because
decline within just two months of tardive dyskinesia, characterized by these drugs are often given to sedate
starting the drugs; of these, more muscle stiffness, tics, tremors and or calm patients with dementia,
than half found that their memory other awkward movements. whereas it appears that they are also
improved as soon as they stopped The arrival of clozapine (Clozaril) speeding up and worsening the

WDDTY Dangerous drugs 43

Drug-induced disease

process of cognitive decline. patients in the active-treatment to foreign invasion by toxins and
Nevertheless, the most compelling groups were any calmer than those bacteria. Without these gangliosides,
evidence comes from autopsy studies who were simply taking sugar pills, we lose myelin and entire neurons,
that have compared patients using although there was one significant and may even die.
antipsychotic drugs with those who difference with quetiapineit was A series of studies by the Institute
did not. associated with significantly greater for Medical Research in Belgrade,
In one study by the Wolfson Centre cognitive decline (BMJ, 2005; 330: 874). Yugoslavia, has demonstrated that, at
for Age-Related Diseases at Kings Antipsychotics also appear to least in ratsso it may not apply to
College London, those whod been shrink the volume of the frontal lobes humanschronic doses of Valium
given neuroleptics had a 30-per-cent of the brain by 0.2 per cent per year, (diazepam) led to the loss of 46 per
greater density of amyloid plaques according to a University of Iowa cent of gangliosides in the cere-
and 65- to 367-per-cent more study (Arch Gen Psychiatry, 2003; 60: bellum within six months. After a
neurofibrillary tangles than those 58594). Other studies have shown short period of total drug withdrawal,
who were free of neuroleptic drugs size reductions in a variety of areas of the rat brain still had not fully
(Int J Geriatr Psychiatry, 2005; 20: 8725). the brain with both older (halo- recovered (Physiol Res, 1999; 48: 1438).
Moreover, in a similar US study, peridol) and newer (olanzapine) When the researchers repeated
102 patients with schizophrenia antipsychotic medications (Arch Gen the study in 2002, focusing especially
showed evidence on autopsy of brain Psychiatry, 2003; 60: 58594). on the effects of the drug on various
deterioration that was suggestive of What is coming to light is a clear regions of the brain, they found
Alzheimers or some other form of association between antipsychotic significant reductions of gangliosides
dementia. The signs were present in drugs and cognitive decline. In a in the hippocampus, cerebral cortex
74 per cent of those whod been painstaking English survey, every and cerebellum, as well as increases
given antipsychotic drugs, but in only case of dementia recorded on a of simple gangliosides in other areas
36 per cent of those whod died prior dementia register during 19931994 (Neurol Sci, 2002; 23: 6974). These
to the advent of these drugs (Alzheimer was examined. Researchers studied findings are consistent with those of
Dis Assoc Disord, 1994; 8: 21127). the patients diagnoses and treat- many human neurological diseases,
In other words, taking anti- ments from their various medical including Alzheimers.
psychotics more than doubled the carers and interviewed their next of Indeed, in a 1993 British study,
patients chances of developing kin, then matched these patients to a researchers took computed tomog-
dementia. similar group of elderly people living raphy (CT) brain scans of long-term
The worst combination of all is in Southeast London. benzodiazepine users and compared
taking an antipsychotic together Of the patients on the register, 13 them with those of drug-free
with an antidepressant, which per cent had a past history of controls. The scans revealed that the
appears to quadruple the speed at psychiatric treatment, and the use of drug users had a reduction of brain
which the disease develops (J Neurol psychiatric drugs was three to four tissue in their frontal and occipital
Neurosurg Psychiatry, 2007; 78: 2339). times higher among those whod lobes, as well as in the left caudate
Whats more, Alzheimers patients gone on to develop dementia (Age nucleusareas that are crucial for
who are given an antipsychotica Ageing, 1998; 27: 1818). cognitive function (Psychiatry Res, 1993;
common practice, usually to sedate 48: 13544).
themhave double the usual risk of Benzodiazepines At present, in the US alone, six
death. In a major study involving In addition to the major anti- million patients are being treated for
various centres across the UKthe psychotic drugs, benzodiazepine dementia at a cost of $90 billion, or
first independent study of its kind tranquillizers and sleeping pills are one-third of all Medicare bills. This
not paid for by a drug companyless also responsible for cognitive means that 1 per cent of the entire
than half the patients (46 per cent) decline. One Argentinian study noted gross domestic product of the US is
taking an antipsychotic were still evidence that sleeping pills, which being spent on a mostly iatrogenic
alive at the two-year follow-up. After are often handed out without a (doctor-induced) condition.
three years, only 30 per cent of those prescription in that country, led to Medicine has reached the point
taking antipsychotics were alive severe memory and cognitive where it is chasing its own tail,
compared with 59 per cent taking a impairment, and delirium (Vertex, attempting to mop up with yet more
placebo (Lancet Neurol, 2009; 8: 1517; doi: 2001; 12: 2725). drugs and treatments a vast and
10.1016/S1474-4422(08)70295-3). Newer studies now show that this costly problem that it has itself
In another UK study that was effect has to do with an effect on caused in the first place.
focused on care facilities in the gangliosides in the brain. These Evidence is mounting that one of
North East of England, the London- molecules, which contain fat and the major toxic insults to the brain is
based researchers compared the sugar, are present to a large extent in the mercury from amalgam fillings,
efficacy of the antipsychotic quetia- brain lipids and on the surface of but this effect may be eclipsed by
pine, the cholinesterase inhibitor every neuron. They are essential for the dangers we face from the modern
rivastigmine and a placebo in regulating cell growth, maintaining medical response to ageing.
calming institutionalized patients the integrity of the material con- Keeping bright and alert in old age
with dementia. Neither of the tained within cells, and responding requires a few simple practices:

44 WDDTY Dangerous drugs

regular exercise; eating an anti- connected through a social network.
oxidant-rich wholefood diet along However, now there is one more
with good fats; minimizing toxic simple homily to add to the list: avoid
exposure to heavy metals; engaging in as many prescription drugs as you
regular brain workouts (crossword can.
puzzles or reading); and staying Lynne McTaggart

WDDTY Dangerous drugs 45

Drug-induced disease

Anticholinergic drugs: the

stupid pills drugs on their own for incontinence,
high blood pressure or allergies are
A giant class of drugs has likely to suffer from impaired physical
been implicated in the suffered a 50-per-cent greater decline function.
in functionality compared with those This was shown in a study of 3000
development of dementia given only cholinesterase inhibitors seniors, 40 per cent of whom were
and loss of physical [for Alzheimers (AD)]. taking anticholinergics. Patients whod
functionality Those given both drugs dropped started out needing only limited
1.62 points per quarter on the scale for assistance in a physical activity were
nticholinergic drugs, widely entirely dependent on assistance one

daily living function, while those given
prescribed to the elderly for the single drug for AD declined 1.08 year later. These findings were pre-
everything from incon- points. Those starting out with lower sented at the American Geriatrics
tinence to ulcers, can hasten functionality had no further decline Society meeting in Washington, DC, in
an older persons decline. with both drugs compared with single May of this year. According to the
Recent studies carried out in the US therapy (J Am Geriatric Soc, 2008; 56: researchers, these effects were seen
found that nursing-home patients 84753). However, the research-ers even in older adults who had normal
taking dementia and incontinence concluded that the tests they memory and cognitive abilities.
drugs at the same time had a 50-per- used were not sensitive enough to The effect is essentially that of a
cent faster rate of physical decline determine whether taking both drugs three- to four-year increase in age,
compared with those taking only together increased mental decline. said Sink. So someone who is 75 in
dementia drugs. Nevertheless, according to the our study and taking at least one mod-
Anticholinergics work by blocking studys lead author, Kaycee Sink, the erately anticholinergic medication is
impulses in the parasympathetic decline was analogous to a nursing- at a similar functional level to a 78 to
nervous system, responsible for the home resident who initially required 79 year old.
involuntary actions of smooth muscle only limited assistance suddenly Earlier studies suggested that drugs
in many parts of the body. They also becoming completely dependent on for incontinence may be associated
prevent the neurotransmitter acetyl- others to help him perform his daily with cognitive decline.
choline from binding with its receptors routine. The most worrying aspect of these
in nerve cells. The researchers believe that the studies is the sheer number of elderly
Three types of these drugs are used results may be due to an oppositional people whose decline is being hasten-
for problems such as ulcers, bladder effect between the two sorts of drugs. ed by polypharmacy. Dementia and
spasm, heart arrhythmias, motion Dementia drugs such as donepezil incontinence represent two of the
sickness, Parkinsons and control of (Aricept) and galantamine (Raza-dyne) most common conditions for which
blood pressure, and as muscle relax- increase acetylcholine, whereas the drugs are dispensed in nursing homes.
ants or pre-anaesthetics. Perhaps the anticholinergics do just the opposite. According to Sink, nearly a third of all
best-known examples of this drug The team concluded that such patients taking anticholinergics also
family are Zantac (ranitidine) and pharmacological opposites would take a drug for incontinence.
nifedipine (Adalat, Procardia). cancel out the effectiveness of either In this instance, Alzheimers may
In this latest study, researchers or both drugs. not be all in the patients head. With
examined 3536 nursing-home resi- However, even on their own, anti- this class of drugs, a patient may be
dents, aged 65 and older, who were cholinergics may lead to functional trading incontinence for incapacity.
taking a bladder anticholinergic (oxy- decline. Older adults taking these Lynne McTaggart
butynin or tolterodine) for incon-
tinence. They then carried out
repeated analyses to assess the effects
Dementia or side-effects?
of the two drugs on cognitive function,
u Loss of coordination
and also examined any changes in daily
u Disorientation
activities. Around 10 per cent of the
u Agitation
residents were taking both drugs.
u Confusion
They found that the combination
u Short-term memory loss
of drugs most affected those whod
u Inability to concentrate or maintain a train of thought
started out with higher levels of
u Illogical thinking
functioning in activities such as
u Incoherent speech
personal hygiene, dressing, bed
u Muscle jerks
mobility, eating and toileting. Among
u Visual and auditory hallucinations.
these residents, those given both drugs

46 WDDTY Dangerous drugs

Diabetes: epidemic by prescription
Dr Lisa Landymore-Lim, a British chemist specializing in
immunology and biomedical chemistry, became curious
about the explosion of childhood illnesses such as
asthma and diabetes, and carried out a pilot study of
drug-prescribing among juvenile diabetics. In 1994,
WDDTY published her initial findings. Here is her
evidence for suggesting a link between the excessive use
of antibiotics and diabetes.

ases of chemicals and drugs destructive agents that have been

C causing temporary and per-

manent insulin-dependent
dia-betes (IDD) are well
documented in the medical lit-erature
(Pharmacol Rev, 1970; 2: 485518; J Rheumatol,
implicated in the onset of cancer.
Other chemicals known to be
capable of producing diabetes in
humans include the drugs dapsone,
used in the treatment of leprosy, and
1987; 14: 7325). Unfortunately, such pentamidine isethionate, an anti-
cases dont usually come to the protozoal agent used to treat pneu-
attention of physicians, and most monia in AIDS patients.
patients are completely unaware of However, dapsone and pentamidine
these potential hazards. bear little structural resemblance to one and pentamidine with the drugs
Two of the best-known chemicals streptozocin and alloxan, except that frusemide and chlorthiazide, diuretics
capable of damaging pancreatic beta dapsone does contain electronegatively reportedly associated with the onset
cellsresponsible for the production charged oxygen atoms that are double- of diabetes, also reveals structural
of insulinare the antibiotic strep- bonded to sulphur (instead of carbon). similarities. In frusemide, once again
tozocin (Zanosar, also used in Both drugs also have electronegative we see the electronegative sulphonyl
chemotherapy) and the chemical terminal amino (NH2) groups attached (S=O) group and a terminal amino
alloxan. These drugs are routinely used to, or in close proximity of, a benzene (NH2) group, whereas chlorthiazide
in animal experiments to study ring. has two SO2 groups and a terminal
diabetes. Vacor, a rat poison, has also Nevertheless, comparison of daps- NH2.
been reported to cause the disease.
There is a structural similarity
between the chemicals streptozocin, Dispensing habits in the UK
alloxan and Vacor: in each, there is at
least one oxygen atom joined by two
Region Rates per 100,000 of incidencea
bonds to a carbon atom (C=O),
forming a carbonyl group, which is
East Anglia 17.7b
flanked on each side by a nitrogen (N)
Wessex 17.1c
Northern 15.8c
This is of interest because carbonyl
Mersey 15.8c
groups and nitrogen atoms can be
Oxford 15.2c
considered reactive species due to
Yorkshire 14.9c
their excess of negative charge. This
North Western 14.6c
means that they are electron-rich and,
Trent 13.5c
thus, have an affinity for positively
South Western 13.4c
charged species such as zinc ions
West Midlands 13.3c
(Zn2+). Thus, they behave like mag-
SE Thames 13.1d
nets, attracting oppositely charged
SW Thames 12.4d
NE Thames 11.8d
Insulin is stored in the pancreas
NW Thames 8.0d
together with zinc. In fact, the pan-
creas has the highest concentration of aof diabetes in children under 15 years of age; bhigh; dmedium; dlow
zinc in the body, making it potentially
NB: This shows more than a twofold variation in incidence between the North
a major target for chemical attack.
West Thames region and East Anglia. What could account for such variation
In addition, double-bonded oxygen
between area health authorities that are situated in close proximity? Could it be
groups are also potential sources for
that dispensing practices are a factor in the onset of diabetes?
the formation of free radicals, those

WDDTY Dangerous drugs 47

Drug-induced disease
Indian J Exp Biol, 1982; 20: 934).
It has also
NIDD: low-grade poisoning? been reported that penicillin interacts
with zinc (J Pharm Pharmacol, 1966; 18:
Non-insulin-dependent diabetes (NIDD), where the diabetic symptoms are not 72938).
severe enough to warrant the use of insulin, is, in the present authors opinion, So, it is conceivable that a chemical
simply subclinical insulin-dependent diabetes. Many patients who are not such as penicillin circulating in the
treated with insulin have abnormally high blood-glucose levels and often bloodstream could be attracted to the
eventually require insulin. beta cells of the pancreas, which
One reason why insulin-dependent diabetes (IDD) and NIDD have been contain zinc. This could result in the
considered two separate and distinct disorders is that NIDD is most commonly displacement of insulin bound to zinc
detected in mature adults and islet-cell antibodies are not found in such and chelation of penicillin to zinc,
patients. However, if chemicals are capable of causing diabetes and with thereby changing the acidity within
exposure taking place over many years, antibody levels in NIDD may be low the cells as new, different bonds are
as the onset of the disease is likely to be much more gradual. formed. This, in turn, could cause the
The idea that IDD and NIDD are essentially the same disorder (apart from insulinzinc aggregates to dissolve,
differences in the degree of insulin-producing impairment) is supported by the leading to a marked increase in
following findings: osmotic pressure and cellular rupture.
u Some 50 per cent of newly diagnosed IDD children do not have detectable It is then possible that such
islet-cell antibodies chemical changes within the pan-
u Some 8 per cent of non-diabetics have been found to have islet-cell creatic beta cells might activate the
antibodies bodys immune-defence system, result-
u Many NIDD patients eventually require insulin therapy ing in the formation of antibodies
u NIDD has been found to be as common as IDD in a study of school children directed against the beta cells in an
in Japan. attempt to bind and destroy them, as
they are now seen as being foreign to
the body.
Such groups are not commonly similarity with chemicals known to This may account, at least in part,
found in drugs. In the American cause diabetes. for the presence of islet-cell antibodies
Hospital Formulary Service Drug To summarize, the chemicals and in the blood of many newly diagnosed
Information database, which lists some drugs currently known or suspected to diabetics. And if this is so, the agent
1000 drugs, less than 5 per cent have be associated with a risk of diabetes that caused the diabetes would be the
either an amino group or a carbon appear to have a primary amine (NH2), chemical that led to rupture of the
atom bound to a benzene ring. a carbonyl (C=O) group close to a pancreas cells, but not to the pro-
Sulphonyl groups, however, are nitrogen or an oxygen atom, and S02 or duction of antibodies, as the cells
commonly found in thiazide diuretics NO2 groups. Primary amines and of the pancreas have already been
and sulphonamide drugs. Alarmingly, oxygen atoms bound to carbon, damaged.
in Australia, diuretics like hydro- sulphur or nitrogenall considered This is an important distinction as,
chlorthiazide (identical to chlorthia- reactive species due to their negatively after the discovery of islet-cell anti-
zide except for an additional hydrogen charged centreswill bind to zinc bodies, the current scientific thinking
atom) are given to young women to under the right conditions by a process as to the origin of diabetes has centred
treat premenstrual water retention. known as chelation, a form of tight on its being an autoimmune disorder,
Indeed, diuretics are among the top chemical attachment. causing the body, for some unknown
most frequently prescribed drugs in The pancreas, being a rich source reason, to manufacture antibodies
the West. If drugs such as thiazides of zinc, could therefore be a potential directed against pancreatic beta cells,
are causing diabetes, then it comes target for attack by zinc-seeking damaging their ability to produce
as no surprise that the incidence of chemicals. Indeed, it has been sug- insulin. This scenario implies that it is
diabetes is increasing in adults. gested that chemicals that can cause the patients constitution (immune
There have also been reports that diabetes may do so by interacting with function) that is at fault.
some antihypertensives (drugs pres- zinc in the insulin-secreting beta cells However, if chemicals and drugs
cribed to control high blood pressure) of the pancreas (Mol Pharmacol, 1985; 27: can cause diabetes, there is every
may also cause diabetes. One of these 36674). likelihood that both IDD and NIDD
is the calcium channel-blocker This suggestion is supported by which in many Western countries
nifedipine. Again, although the overall the fact that diabetes arising from today has reached epidemic propor-
structure of this drug is not like any of chemical exposure is accompanied by tionsare predominantly the result
the other drugs previously mentioned, a loss of detectable zinc from the of chemical exposure by way of pres-
it does contain several electronega- pancreatic beta cells (Arch Exp Pathol cription drugs.
tive double-bonded oxygen groups, Pharmakol, 1952; 216: 45772), and that zinc
including an NO2 group bound to a injected into animals before exposure Possible zincdrug interaction
benzene ring such as is found in Vacor to a diabetes-causing chemical will If its true that drugs, or the chemical
rat poison. So, indeed, it is evident that protect the animals against developing byproducts formed in the body fol-
nifedipine shares some structural the disease (Anat Record, 1951; 109: 377; lowing their ingestion, have an affinity

48 WDDTY Dangerous drugs

for zinc, then when they enter the
bloodstream and pass through the Drugs causing diabetes
pancreas, they will bind to the zinc
in the islet cells of the pancreas. This One drug that appears to have the potential to cause diabetes is the barbiturate
could displace someif not allof phenobarbitone, due to its similarity in structure to the chemical alloxan.
the six insulin molecules that are Phenobarbitone and other barbiturates used in human medicine also bear some
temporarily bound to zinc in the resemblance to alloxan.
pancreas. Chemical modifications of alloxan have also been shown to cause diabetes
Such an interaction could change in some animal models. So, all of these chemicals, which share structural
the acidity of the cells, causing them similarities, can cause diabetes in animals. Nevertheless, Lisa Landymore-Lim
to burst as the osmotic pressure within is unaware of any investigations into their potential diabetogenic effects in
them becomes too great. The result humans.
would be irreversible damage to the The following drugs could be considered the major potential culprits in
cells that, in turn, could result in causing diabetes:
activation of the immune system as it u Antibiotics
detects a deformed cell, which it Penicillins (such as amoxycillin)
would regard as foreign (abnormal Cephalosporins (structurally similar to penicillin)
in form). Erythromycin
This would trigger the formation of u Tranquillizers
antibodies, proteins that are directed Barbiturates (structurally similar to alloxan)
against such foreign (non-self) agents Benzodiazepines
within the body, and explain why many u Other drugs
newly diagnosed diabetics have islet- Syntocinon (synthetic hormone, used to induce labour, containing
cell antibodies in their blood. ergometrine)
However, if this were the case, these Ergometrine (used to stop postpartum bleeding)
islet-cell antibodies would simply be Paracetamol (analgesic).
formed as a result of preexisting
damage to the pancreas, but would
not be the agents responsible for the already destroyed during its devel- personal communication).
destruction of the insulin-producing opment, it would be unlikely to present The probability of binding (chela-
capacity of the pancreasas is cur- any of the clinical symptoms currently tion) between zinc and organic
rently thought. associated with diabetes. However, compoundsthat is, compounds
If chemicals such as drugs or their after birth, the child may be expected containing carbon, nitrogen and
byproducts are not responsible for to run out of its insulin-producing oxygenis high. Such binding usually
eliciting an immune response that capability at an earlier age than a baby occurs between the negative-ion-
results in the formation of antibodies, that is exposed to the same amount rich centres of either the oxygen or
the unanswered question then of toxic chemical, but after birth. In nitrogen groups of the chemical and
remains: what is it that triggers the the latter child, a smaller proportion of the positively charged zinc (Zn2+) ion.
immune system to produce these the pancreas would be affected as its In the case of insulinzinc complexes
antibodies? exposure was later in its development. found naturally in the pancreas, the
On the other hand, if some Damaged pancreatic cells, unlike liver binding is reversible, as it enables
chemicals are indeed capable of cells, are not replaced as they lack any insulin to be stored until required.
destroying the ability of pancreatic significant capacity for regrowth. Whatever the route of destruction of
beta cells to secrete insulin, as is So, as the body weight of both these the pancreas ability to secrete insulin,
known to occur in those who have infants increases after birth, the one it is worthwhile noting that some of
ingested the rat poison Vacor, then it with the lower level of insulin- the drugs that diabetic children are
is conceivable that the damage may producing capability would be exposed to during fetal development
be gradual, with just a portion of the expected to exhibit signs of diabetes are structurally similar to each other.
pancreas being destroyed with each sooner, at an earlier age. For example, in the survey of diabetic
chemical attack. The drug penicillaminewhich is children that I carried out, one child
Also, it would appear to be logical to also one of the breakdown products of was exposed to Asacol (mesalamine)
suppose that children who are exposed penicillinis an effective chelator of and another to paracetamol. The
as fetuses and newborns to such an metal ions, including zinc, and is used structure of Asacol is similar to para-
agent might become diabetic at a in medicine as chelation therapy for aminophenol, a highly toxic chemical
younger age than those exposed to the the reduction of toxic levels of zinc formed in the body in tiny quantities
same agent as babies or children, and salts. Also, although erythromycin was following paracetamol (acetamino-
may require only one exposure to cause reported some 25 years ago as not phen) breakdown.
damage if it occurred in utero or soon binding to zinc, it is now known that Whats more, Asacol and penicilla-
after birth. it can be made to react in vitro [in mine both have an amine (NH2) and a
For example, if a fetus of 25 weeks the lab] in a one-to-one ratio (Brocades carboxyl (COOH) group.
has half of its insulin-producing cells Pharma [now known as Yamanouchi Europe], a A drug connection would also

WDDTY Dangerous drugs 49

Drug-induced disease

account for another mysterious feature despite the presumably higher [the Thames region with the lowest
of diabetes: that only the beta cells of population density of children in the incidence of diabetes in under-15s
the pancreas are destroyed. The alpha latter. during 1988] was also the region with
and delta cells of the pancreas, also In other words, if all children were the lowest number of prescriptions per
located in the islets of Langerhans at equal risk of diabetes irrespective person in 1981 and in 19905.6 and
where the beta cells are, are not of where they lived, the expectation 5.9, respectively.
damaged in diabetes. It is only the would be to find more diabetic chil- By way of comparison, the SE
zinc-containing beta cells that are dren in the urban areas. Thames area (the Thames region with
damaged. This selective destruction Furthermore, it appears that some the highest incidence of diabetes) was
may well be caused by chemicals with of the dispensing practices in the the Thames region with the highest
an affinity for zinc. countryside were considerably more number of prescriptions per person for
affluentdespite being supported by 1981 and 1990 (6.3 and 7.0,
UK dispensing practices fewer GPscompared with those in respectively).
When considering diabetic children in the outer-London areas. Indeed, some Although these data do not include
the same family, rather than heredity, surgeries had recently been purpose- prescriptions issued by dispensing
the cause may be the family doctor. built, and at considerable cost. It was doctors, the percentage of dispensing
If the familys physician commonly also noticeable that in some of these doctors in both of these Thames
prescribes antibiotics to babies and practices, antibiotics were apparently regions is approximately the same.
children, and if one accepts that being liberally prescribed to babies However, the SW Thames region,
antibiotics may be implicated in the and children. The small areas looked which has a low percentage of dis-
onset of diabetes, then it would not be at were located in area health pensing doctors (6 per cent), but
surprising to find more than one authorities with a high incidence of ranked second highest for incidence
diabetic child in the same family. diabetes. of diabetes of the four Thames regions
The table shown in the box on page This raises the question of whether (see box, page 47), was reported in
47 shows the geographical variation in the proportion of dispensing doctors 1985 to have the highest rate of
the incidence of diabetes in England might be related to the incidence of induced births in England (23.9 per
among the under-15-year-old age diabetes in children. If drugs such as cent), compared with an average of
group. East Anglia, a predominantly antibiotics were implicated in any 17.2 per cent for the other Thames
rural area, has the highest incidence, way with the onset of diabetes, and if regions (Francome C. Changing Childbirth:
whereas the four Thames regions, dispensing doctors prescribed them Interventions in Labour in England and Wales.
areas of higher population density more liberally perhaps as a result of London: Maternity Alliance, 1989).
and pollution, have the lowest. The financial incentives, then it might be Since dispensing doctors are more
incidence in East Anglia is more than reasonable to expect to find a higher liberal in handing out drugs, then it
double that of the North West Thames incidence of diabetes in country vs might be expected that an area with a
region. city children. high proportion of dispensing doctors
This pattern of a rural area having The North Western and Mersey would also have a high incidence of
a higher incidence of diabetes than an regions, which both have a medium diseasewhich is indeed the case
urban region is also seen in Scotland. incidence of diabetes and yet a low here.
In the UK, doctors are allowed to number of dispensing doctors, are Furthermore, regions with a higher
dispense their own drugs for patients both, incidentally, regions with the number of prescriptions per person
who are living more than a mile away highest number of prescriptions also had a higher incidence of
from the closest pharmacy. Conse- (excluding those dispensed by pres- diabetes.
quently, although few GPs in builtup cribing doctors) per person in England The idea that drugs can cause
areas dispense their own drugs, in rural for 1981 and for 1990. They are also diabetes is not new. What is novel is
areas, the proportion of dispensing the regions with the greatest increase the suggestion that there are drugs
practices can be rather high. in the number of prescriptions per in common use that may be partly
In one study comparing children person in England between 1981 and responsible for the epidemics
living in the Cambridgeshire and 1990an average increase of 25 per currently seen in many industrialized
Wessex Areas, the health authorities centcompared with around 8.7 per countries today.
data showed that a high proportion cent for the four Thames regions over Lisa Landymore-Lim
of diabetic children lived in the the same time period. Dr Landymore-Lim is a chemist who
countryside and not in the towns, In addition, the NW Thames area specializes in immunology.

50 WDDTY Dangerous drugs

HRT: the latest cancer risk
Just when it looks as if it couldnt get any worse for
HRT, a new study shows that it causes lung cancer
nyone with shares in hor- 140 extra cases during the eight-year

A mone replacement therapy

(HRT) is in the doldrums.
HRT was touted as the
modern-day equivalent of the fountain
of youthuntil 2002, when the US
follow-up, accounting for 5 per cent of
all cases of the cancer.
The risk of having the disease were
the same regardless of how long the
drug was taken, which formulation was
by HRT (Epidemiology, 2009; 15 May: doi:
10.1097/EDE. 0b013e3181a71279).

Womens Health Initiative (WHI) study, used, how much oestrogen was Fewer cases after the facts
one of the largest-ever studies of these included in the mix and what sort of Following the disclosures of the WHI
drugs, discovered that women taking delivery method was chosen. trial, breast cancer rates fell by 13 per
HRT were more likely to have breast As ovarian cancer is difficult to cent among more affluent women in
cancer, ovarian cancer, stroke and heart detect and is often fatal, such a risk California, but only by 7 per cent in
disease. should not be brushed aside, the rural areas. When researchers from the
And now, new evidence from the Copenhagen researchers noted. Northern California Cancer Center
WHI data shows that the use of HRT investigated the discrepancy, they
during the menopause increases lung HRT to blame found that women in the more rural
cancer by 60 per cent after five years. Up to now, medicine has tended to areas had not heard about the link
Dr Rowan Chlebowski, a medical blame a familial predispositionthat between HRT and cancer, and so had
oncologist at Harbor-UCLA Medical is, a family history of breast cancer and continued taking the drugswhich
Center in Los Angeles, CA, analyzed the presence of certain predisposing would again tend to point the finger at
the WHI statistics, and found a link geneson many inci-dences of breast HRT (BMC Med, 2009; in press).
between prolonged HRT use and non- cancer, particularly in women using After the WHI results were reported,
small cell (NSC) lung cancer. HRT. Nevertheless, the latest trawl Wyeths products took a hammering,
Although most of the adverse through the WHI data shows that HRT and their use declined
publicity after the WHI study focused shoulders much of the blame. by 50 per cent. Nevertheless, sales of
on the breast cancer risk, this is the Epidemiologists from the Univer-sity the oestrogen-only drug Premarin and
first time that a link between HRT and of Rochester Medical Center, in New various cream formulations still
lung cancer has been identified. It also York, followed-up the more than 16,000 constitute a business totalling up to
happens that NSC lung cancer is the postmenopausal women given either one billion dollars per year.
leading cause of death in women. HRT or a placebo during the five-year Last month, the US Food and Drug
The most vulnerable women were WHI study, which was abruptly Administration added a final nail in the
smokers using HRT, who accounted for abandoned when the health risks HRT coffin with a boxed warning for
slightly more than half of all cases of emerged. When they evaluated the 349 Prometrium, a progesterone drug,
NSC lung cancer. In the WHI study, the women whod developed breast cancer, warning of the WHIs results showing
researchers found one extra they could find no link with a family increased risks of heart attack, stroke,
death from this for every 100 women history. invasive breast cancer, blood clots and
using Prempro, Wyeths combination The researchers concluded that a deep vein thrombosis, and a greater risk
oestrogenprogestin HRT drug. family history and hormones have of dementia, among those taking
independent and non-interacting combined oestrogens and progesto-
Ovarian cancer risk effectsin other words, the cases of gens of any variety.
This announcement, made at the cancer were most likely entirely caused Lynne McTaggart
annual meeting of the American
Society of Clinical Oncology in May, The current risks of HRT
coincided with the release of the
findings from a large-scale, long-term
According to the US Womens Health Initiative study, hormone therapy
Danish study showing that women who
increases your chances of developing the following diseases by these
take HRT increase their risk of ovarian
cancer by 38 per cent (JAMA, 2009; 302:
u Coronary heart disease-related events, 29 per cent
u Stroke, 41 per cent
The study, which included more than
u Deep vein thrombosis, 200 per cent
900,000 women aged 5079, found
u Blood clot in lungs, more than 200 per cent
that the current use of hor-mones
u Invasive breast cancer, 24 per cent
accounted for a 38-per-cent greater
u All cancers among previous users, 86 per cent
chance of ovarian cancer. This
u Ovarian cancer, 38 per cent
translates to one extra case every year
u Lung cancer, 60 per cent.
for every 8300 women using HRT, or

WDDTY Dangerous drugs 51

Drug-induced disease

The big cure-all unmasked

The great all-purpose preventative for cholesterol has
been found to cause prostate cancer

tatins, the gold standard of index of more than 30 kg/m2

S cholesterol treatment,
have become the liver
tonic of the modern age.
Doctors hand them out for
everything from osteoporosis to
increased their risk by 1.5 times
over overweight non-users. Also,
the risk increased to 1.8 times with
statin use for five or more years
(Am J Epidemiol, 2008; 168: 25060).
senile dementia, as early studies But the Seattle evidence is only
suggest that they may have the latest to challenge the myth of
preventative effects. cancer prevention. A University of
When early laboratory evidence Athens review of 19 epide- evidence of statin use and cancer
showed that statins induce miological studies found no incidence. Their review of 14
apoptosis (cell death) and reduce evidence of a protective effect with studies found no evidence to
prostate cancer cell growth and statins and even suggested that the support claims that statin use can
spreading (Cancer Epidemiol Biomarkers earlier evidence of lowered risk was protect against malignancies of
Prev, 2008; 17: 8894 ), medicine just coincidental (Int J Cancer, 2008; the blood, such as leukaemia (Br J
concluded that statins were a 123: 899904). Clin Pharmacol, 2007; 64: 25562 ).
potent cancer preven-tative (J Natl More detailed analyses found a They also found no evidence that
Cancer Inst, 2006; 98: 181925) . Early lower incidence of advanced statins can significantly reduce the
studies bolstered this view, offering cancer, but no reduction in the risk of colorectal cancer, although
preliminar y evidence that long- risk of overall prostate cancer ( Curr they concluded that there might
term statin use could prevent Opin Urol, 2008; 18: 3339 ). An even be some effect with higher doses (J
cancers of the breast, prostate, larger meta-analysis of 35 Clin Oncol, 2007; 25: 34628 ). The same
blood and colon. randomized controlled trials methodology also found no
Studies of populations with showed a link between the drug evidence that statins can reduce
prostate cancer found links and developing cancer, depending the risk of either pancreatic or
between statins and the prevention on the patients age: the older the breast cancers (Am J Gastroenterol,
of more advanced forms of the man, the more likely he was to 2008; 103: 264651; J Clin Oncol, 2005; 23:
disease ( Curr Opin Urol, 2008; 18: develop cancer (J Clin Oncol, 2006; 24: 860612).
3339). Doctors were particularly 480817). Yet another research team, from
enthusiastic when a case-control Another meta-analysis of prava- the Department of Epidemiology
study found a cancer risk statin in elderly patients confirmed and Survellance Research at the
reduction of 20 per cent with an association between the drug Ameri-can Cancer Society, found
statins (J Clin Oncol, 2004; 22: 238894). and an increased risk of cancer that neither short- or long-term
Now, that reputationthat with increasing age (CMAJ, 2007; 176: (five years or more) use of the drug
statins are a powerful cancer 64954). prevented colorectal cancer (J Natl
preventativehas been sullied As for other forms of cancer, the Cancer Inst, 2006; 98: 6972 ).
with the latest findings that statins Department of Pharmacology team Similarly, a Boston University
may actually cause prostate cancer at the University of Athens School study of more than 3600 patients
in overweight men. Researchers at of Medicine has systematically in Massachusetts could also find no
the Fred Hutch-inson Cancer examined and combined all the protective effect other than a lower
Research Center in Seattle, WA,
discovered the link while studying
more than 1000 cases of prostate
cancer, diagnosed between
Take as little as possible
20022005, compared with a
similar number of age-matched If you must take a statin drug, take the smallest dose possible. New
controls. evidence shows that even the minimum daily dose of 20 mg/day causes
Although there was no risk of potentially fatal muscle pain and weaknessand may even lead to
developing the disease in normal- complete breakdown of muscle tissue (N Engl J Med, 2008; 359: 78999).
weight statin users, including Higher doses or taking the drug with other drugs had a magnifying effect,
those who had taken the drugs for causing a far higher incidence of myopathy than the official figures claim.
more than 10 years, overweight The latest evidence shows that as much as 1.6 per cent of patients develop
men those with a body mass muscle weaknessthats 128,000 patients in the US alone.

52 WDDTY Dangerous drugs

risk of stage IV (advanced, metas- 90,000 participants involved in all also shows that statins dont
tasizing) cancer among statin studies claiming a protective effect prevent fractures or type 2 diabetes
users, an association that the against all cancers. Again, the data either ( Pharmacoepidemiol Drug Saf,
authors believe requires indicate that no type of cancer is 2007; 16: 62740 ; Curr Med Res Opin, 2008;
confirmation (J Natl Cancer Inst, 2007; affected by statin use (JAMA, 2006; 24: 135962). This kicks away several
99: 3240). 295: 7480). platforms on which the drugs
The final blow was dealt by a Aside from the damning evidence reputation as a preventative
University of Connecticut School of against its role as a cancer treatment has been based.
Pharmacy meta-analyses of nearly preventative, the latest evidence Lynne McTaggart

WDDTY Dangerous drugs 53