Basic & Clinical Pharmacology & Toxicology, 107, 883–886 Doi: 10.1111/j.1742-7843.2010.00590.

Does Pregabalin (Lyrica) Help Patients Reduce their Use

of Benzodiazepines? A Comparison with Gabapentin using
the Norwegian Prescription Database
Jørgen G. Bramness1,2, Pl Sandvik3, Anders Engeland2,4 and Svetlana Skurtveit1,2
1
Norwegian Centre for Addiction Research, University of Oslo, Oslo, Norway, 2Department of Pharmacoepidemiology, Division
of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway, 3Department of Laboratory Medicine, Children’s and Women’s Health,
Norwegian University of Science and Technology, Trondheim, Norway, and 4Department of Public Health and Primary Health Care University
of Bergen, Bergen, Norway
(Received 21 December 2009; Accepted 11 March 2010)

Abstract: Pregabalin (Lyrica) may have an anxiolytic effect. It has also been reported that the use of this drug helps prevent
excessive use of benzodiazepines. The aim of the present study was to examine if pregabalin reduced the intake of benzodiaze-
pines. In a pharmacoepidemiological study, we compared pregabalin to the older drug gabapentin (Neurontin) in the Norwe-
gian Prescription Database. The database has total capture of all prescribed drugs outside institutions. We identified all
prescriptions for the two drugs for patients aged 18–69 years between 2004 and 2007. Patients were grouped as psychiatric
patients, patients with epilepsy, patients with neuropathic pain or non-specified users. We measured the use of benzodiazepines
182 days before and after the initiation of treatment with pregabalin and gabapentin. Between 15% and 29% of the patients
were able to stop using benzodiazepines after starting pregabalin or gabapentin treatment. Psychiatric patients who started
pregabalin were able to reduce the amount of benzodiazepines used by 48%, compared to only 14% among starters of gaba-
pentin. This study shows that some patients reduced their use of benzodiazepines substantially after starting pregabalin.

Pregabalin and its older analogue gabapentin are derivates
of c-aminobutyric acid (GABA) and share anti-epileptic
[1], analgesic [2] and anxiolytic [3] properties. In Norway,
both drugs are approved for the treatment of epilepsy and
neuropathic pain. Pregabalin is approved for treating gener-
alized anxiety disorder, but due to the chemical similarities
and marginal pharmacological differences between the
drugs [4], we might expect pregabalin and gabapentin to be
used similarly.
In spite of their chemical resemblance to GABA, neither
gabapentin nor pregabalin seem to possess GABAergic prop-
erties. They inhibit the alpha-2-delta subunit of presynaptic,
voltage-gated Ca2 + channels, diminishing Ca2 + influx in
response to incoming action potentials, thereby decreasing
the release of several excitatory neurotransmitters, including
glutamate [5].
Despite this pharmacology, the resemblance of the two
drugs to GABA has led to awareness of their potential for
abuse and dependence. Their abuse potential has been dis-
cussed by The European Medicines Agency [6] and the
American Drug Enforcement Administration designating
pregabalin as a schedule V controlled substance [7].
Clinically, there is a need for a non-addictive anxiolytic
drug, since benzodiazepines, despite their abuse and depen-
Author for correspondence: Jørgen G. Bramness, Department of
Pharmacoepidemiology, Norwegian Institute of Public Health, PO
Box 4404 Nydalen, NO-0403 Oslo, Norway (fax +47 23 36 89 86,
e-mail j.g.bramness@medisin.uio.no).
dence problems, are still often used in the treatment of anxi-
ety disorders [8]. It has been claimed that pregabalin could
be used as a safe and unproblematic substitute for ben-
zodiazepines [9,10]. There is some indication that gabapentin
may reduce consumption and craving in alcohol-dependent
patients [11] and a case description suggests that pregabalin
may help in benzodiazepine withdrawal [12].
The advent of the Norwegian Prescription Database (Nor-
PD) [13,14], effective from 1 January 2004, made it possible
to study whether starting with new drugs would have an
impact on the consumption of prior drugs [15]. The aim of
our study was to explore if the initiation of pregabalin
reduced the consumption of benzodiazepines by investigating
prescriptions given to individual patients. The related drug
gabapentin was used as comparator.
Materials and Methods
Prescription database. Data were drawn from the NorPD covering
the entire country (4.8 million inhabitants). Since 1 January 2004, all
pharmacies in Norway are obliged, by law, to submit monthly elec-
tronic data on dispensed prescriptions to the Norwegian Institute of
Public Health. The NorPD contains information on all prescription
drugs, reimbursed or not, dispensed at Norwegian pharmacies to
individual patients who live outside institutions [14]. This study
included data from 1 January 2004 to 31 December 2007. The data
collected were: patients’ unique identifiers (encrypted), gender, age,
prescribers’ unique identifiers (encrypted), prescribers’ medical speci-
ality (here: psychiatry, neurology, general medicine or anaesthestics),
date of dispensing and drug information [brand name and defined
daily dose (DDD)]. The indication for prescribing was not recorded

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Basic & Clinical Pharmacology & Toxicology  2010 Nordic Pharmacological Society
884 JØRGEN G. BRAMNESS ET AL.
as such, but several characteristics of the prescription (e.g. doctors’
speciality or reimbursement code) can be used as a proxy for the
indication. Data on age and gender-specific population figures were
taken from Statistics Norway [16].
The drugs. The DDD for pregabalin is set internationally at 300 mg
per day and for gabapentin at 1800 mg [17]. Despite being registered
for several indications, only gabapentin is covered by the Norwegian
reimbursement system on a general basis and then only for the treat-
ment of epilepsy. However, both drugs can be reimbursed for other
indications (epilepsy, psychiatric indication and neuropathic pain)
after special application.
Study group. We studied all patients between the age of 18–69 years
who had been dispensed at least one prescription of either pregabalin
or gabapentin in 2004–2007. These patients were grouped according
to the following criteria: (i) psychiatric patients: all users of the drug
who received their prescription(s) from a psychiatrist or whose pre-
scription was reimbursed as a psychiatric drug; (ii) epileptics: all
users of the drug who received a prescription reimbursed as an
antiepileptic drug; (iii) neuropathic pain: all users of the drug who
received their prescription from a specialist in general medicine, an
anaesthetist or a neurologist and whose prescription was not reim-
bursed as an antiepileptic drug, or patients who had their drug reim-
bursed for a malignancy, trigeminal neuralgia, migraine, for other
pain syndromes or as part of palliative care; or (iv) patients with
prescriptions who fulfilled none of the above criteria (non-specified
users). When patients received multiple prescriptions and fulfilled
more than one criterion, the criteria were given priority in the
following manner: Criterion (i) over criterion (iii), (iii) over (ii) and
(ii) over (iv).
Pharmacoepidemiological parameters. For calculation of 4-year per-
iod prevalence, all individuals aged 18–69 years who had been dis-
pensed at least one prescription for pregabalin or gabapentin during
the 4-year study period were identified. Prevalence rates (number of
users per 100 inhabitants) for each substance were calculated using
census data as denominators.
In order to study the impact on benzodiazepine use of starting
with pregabalin or gabapentin, we identified incident users of pregab-
alin (n = 12,704) or gabapentin (n = 3603). True incident users were
defined as patients who started pregabalin or gabapentin treatment
between 1 January 2005 and 30 June 2007 and who were dispensed
at least two prescriptions of the drug during this period. We noted
the amount of benzodiazepines dispensed during a 182-day period
before or after the first prescription for pregabalin or gabapentin was
dispensed. Benzodiazepines included all dispensed benzodiazepines
in Norway (with market authorization or not) expressed in diazepam
equivalents according to the following calculation: 1 diazepam equiv-
alent (mg) = 1 mg diazepam = 3 mg oxazepam = 0.1 mg alprazo-
lam = 0.25 mg lorazepam = 1 mg bromazepam = 2 mg clobazam =
1 mg nitrazepam = 0.1 mg flunitrazepam = 3 mg midazolam =
0.2 mg clonazepam. Individuals who used benzodiazepines before
starting treatment with pregabalin or gabapentin could either stop
their use or continue. In the latter case, any change in the amount of
benzodiazepines was noted. Alternatively, they could start using
benzodiazepines in the period after their first prescription of
pregabalin or gabapentin.
Results
During the 4-year period of observation, 27,923 individuals
aged 18–69 years (0.23% of the population of this age)
received at least one prescription for pregabalin. The corre-
sponding figure for gabapentin was 13,900 (0.11%). The
average age for pregabalin users was 50 years at the start of
the 4-year period and 58% were female. Age and gender dis-
tribution was no different from that of gabapentin.
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Basic & Clinical Pharmacology & Toxicology  2010 Nordic Pharmacological Society. Basic & Clinical Pharmacology & Toxicology, 107, 883–886
Stoppers, continuers and starters of benzodiazepines
among incident users of pregabalin and gabapentin are
shown in table 1. Among users of benzodiazepines before
prescription of pregabalin or gabapentin, the proportion of
continuers was above 70% for all groups. Among non-users
of benzodiazepines before the prescription of pregabalin or
gabapentin, the proportion of starters was between 14 and
21% for all groups (table 1). Doses (median) of benzodiaze-
pines before starting with pregabalin or gabapentin was five
to ten times lower among stoppers (and starters) compared
to continuers for all patient groups. Among continuers of
benzodiazepine use, there was a striking difference between
psychiatric patients starting with pregabalin and all other
groups. Among psychiatric patients already using ben-
zodiazepines, who started using pregabalin, there was a mean
reduction of 48% in diazepam equivalents in the half year
after starting pregabalin. Also among the non-specified users
of pregabalin, there was a substantial decrease in the use of
benzodiazepines.
Discussion
In this study, we demonstrated that after starting with pre-
gabalin or gabapentin, 15–29% of the patients stopped using
benzodiazepines. Stoppers consumed, on average, fewer ben-
zodiazepines than the continuers, indicating that use of
smaller amounts was more easily stopped. Among continu-
ers, the psychiatric patients starting pregabalin treatment
reduced the consumption of benzodiazepines by 48% while
the reduction among the non-specified users was 39%. For
all the other groups, the reductions in benzodiazepine con-
sumption were smaller. A possible interpretation would be
that pregabalin, but not gabapentin, might have a benzodiaz-
epine sparing effect in patients with anxiety disorders, as
indicated by others [9,10]. However, some patients started
using benzodiazepines after initiating pregabalin or gabapen-
tin treatment, diluting the benzodiazepine sparing effect
somewhat.
There are several limitations to this study. NorPD does
not include medications given to individuals in hospitals and
other institutions. Information on diagnoses or severity of
conditions is not available in the database and patients were
grouped according to other supplementary criteria. The
number of patients being ungrouped, especially among the
users of pregabalin, illustrates this shortcoming. We do not
know if or when the drugs dispensed are actually used. Fur-
ther, the use of medicines could be sporadic; starting and
stopping upon the appearance or reappearance of symptoms
which could occur long after the dispensing date.
However, our data include dispensed drugs rather than pre-
scribed drugs and this rules out primary non-compliance
[18]. Another advantage is that the NorPD includes prescrip-
tions from all practicing physicians, both general practitio-
ners and specialists, prescribing medicines to patients living
outside institutions in Norway. A further strength of this
study is that it provides age- and gender-specific information
for all dispensed prescriptions of pregabalin for the entire
 Table 1.
The use of benzodiazepines (BZD) (in diazepam equivalents) before (continuers and stoppers) and after the start (continuers and starters) of treatment with pregabalin or gabapentin for those who
started pregabalin or gabapentin treatment between 1 January 2005 and 30 June 2007. (Data from NorPD 2004–2007).
Users of gabapentin and pregabalin who also used benzodiazepines
Continued users of BZD Stopped using BZD Started using BZD
BZD Number of Number of Number of
Incident users182 continuers Dose Dose stoppers Dose starters Dose
users of pre-gabalin days 182 days 182 days 182 days 182 days 182 days 182 days 182 days
or gaba-pentin1 before after before after after before after after
Diazepam Diazepam Diazepam
equivalents (mg) %2 change equivalents (mg) equivalents (mg)
n n %3 n %3 median (mean) n %4 median n ⁄ non-users5 %6 median
(i) Psychiatric indication
Pregabalin 588 426 72.4 325 76.3 2820 1479 )48 101 23.7 448 34 ⁄ 162 21.0 100
Gabapentin 163 111 68.1 87 78.4 1900 1225 )14 24 21.6 516 9 ⁄ 52 17.3 400
(ii) Epilepsy
Pregabalin 589 285 48.4 243 85.3 1398 1792 26 42 14.7 250 59 ⁄ 304 19.4 211

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Gabapentin 1154 444 38.5 344 77.5 1615 1511 )18 100 22.5 180 145 ⁄ 710 20.4 140
(iii) Neuropathic pain
Pregabalin 3933 1809 46.0 1377 76.1 1350 1170 )14 432 23.9 200 441 ⁄ 2124 20.8 225
Gabapentin 1269 524 41.3 372 71.0 1014 1090 0 152 29.0 163 148 ⁄ 745 19.9 288
(iv) Non-specific users
Pregabalin 7594 3019 39.8 2177 72.1 2200 1510 )39 842 27.9 155 626 ⁄ 4575 13.7 150
PREGABALIN AND USE OF BENZODIAZEPINES

Gabapentin 1017 355 34.9 264 74.4 1617 1493 )7 91 25.6 125 99 ⁄ 662 15.0 200
1
Incident users of pregabalin or gabapentin were those who received their first prescription between 1 January 2005 and 30 June 2007 and were dispensed a total of two or more prescriptions before
31 December 2007.
2
Percentage change is calculated based on change in each individual user.
3
Percentage of all incident users.
4
Percentage of all incident users also using benzodiazepines.
5
The number of patients starting to use benzodiazepines after starting pregabalin or gabapentin treatment over the number of benzodiazepines non-users.
6
Percentage of those who did not use benzodiazepines before.

Basic & Clinical Pharmacology & Toxicology  2010 Nordic Pharmacological Society. Basic & Clinical Pharmacology & Toxicology, 107, 883–886
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886 JØRGEN G. BRAMNESS ET AL.
population in Norway. This approach eliminates the possibil-
ity of both selection and recall bias.
If, however, pregabalin and gabapentin were to be drugs
of abuse, the benefits of reduced benzodiazepine use might
be questioned. The abuse potential of pregabalin and gaba-
pentin has remained in question, even if the literature on the
subject is small [19–21]. The abuse potential of pregabalin in
particular, but also of gabapentin warrants further research.
Acknowledgements
The study was financed by internal means only, the
authors being independent in their research. All authors had
full access to all of the data in the study and take responsibil-
ity for the integrity of the data and the accuracy of the
data analysis. JGB, PS, AE and SS all had the idea for
this research. JGB and PS wrote the main body of the text.
AE and SS performed the statistical analysis. JGB, PS, AE
and SS participated in the interpretation of the results and
the writing of the ‘Discussion’ section. PS received travel
grants from Glaxo, Wyeth and Astra Zeneca. None of the
other authors have any commercial conflicts of interest to
declare.
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