Lithium Clozapine
 Mood stabilizer  Second generation, atypical
 MoA unknown but related to
second messenger
Mechanism of Formulation
action  Li carbonate (tablets)
 Li citrate (tablets or liquid)
 Treatment of mild to moderate
mania
 Prophylaxis of bipolar affective
disorder (more effect at
preventing manic than depressive
relapse)
 Prophylaxis of recurrent
depression in people who have
not responded to standard
antidepressants, added for
augmentation
 Treatment of aggressive behavior
 Treatment of self-mutilating
behavior
Indications  Prevention and treatment of
steroid-induced psychosis
 Prolonged duration of at least 3
Duration of years due to risk of relapse
treatment following discontinuation
Before
 Bloods (RFTs, TFTs), ECG,
weight, exclude pregnancy
After starting or changing dose
 Serum Li measured after 5 days
Monitoring  Dose adjusted to achieve a
concentration between 0.5-
1mmol/l
 Bloods ideally taken 12 hours
after last dose administered
antipsychotic
 Dopamine receptors –highest
affinity for D4 receptors
 Serotonin receptors
 Adrenergic receptors a1 and
a2
 Muscarinic receptors
 Treatment resistant
schizophrenia (main
indication)
 Tardive dyskinesia
 Psychosis in Parkinson’s
 Huntington’s psychosis
 Resistant mania
For schizophrenics who have not
responded adequately to
pharmacological or psychological
treatment: review dx, establish
adherence and adequate dose and
correct duration. Review
engagement with psychological
treatments and ensure that it has
been offered – family intervention,
CBT. Consider other causes of non-
response e.g. co-morbid substance
misuse (alcohol), concurrent use of
other prescribed medication or
physical illness.
Offer for those with schizophrenia
who has not responded adequately
to treatment despite sequential use
of adequate doses of at least 2
different antipsychotics one of which
should be a non-clozapine second-
generation antipsychotic.
 At least 2 years – due to 75%
risk of relapse in someone
with schizophrenia who stops
their prescribed medication
 Registered with an approved
monitoring system and given a
unique identifying number
 Initiation – inpatient or at day
hospital
Before
 Normal leukocyte count (WBC
>3,500/mm3, neutrophils
>2,000/mm3)
 Bloods – FBC, fasting
cholesterol, lipids, glucose
 Lithium
During treatment
 Check serum lithium levels every
3 months
 RFTs and TFTs – every 9 months
 Monitor weight
 Seek attention if symptoms of
hypothyroidism develop e.g.
lethargy and feeling cold
 If discontinued, dose should be
reduced gradually over a period
of a few weeks as possible
relapse if abruptly discontinued
 Advice about contraception
 Teratogen
 Risk of foetal heart defect,
Ebstein’s anomaly, floppy baby
syndrome, potential thyroid
abnormalties and nephrogenic
diabetes insipidus, miscarriage
Use in women of
childbearing age  Do not routinely prescribed in first
trimester or breastfeeding
 Advise woman who is well and
not at high risk of relapse to stop
drug
o If a woman taking Li is
pregnant – confirmed in
the 1st trimester, well and
Clozapine
levels), ECG, CXR, weight
After initiation
 Plasma levels of clozapine,
norclozapine and ratio can be
measured after 3 weeks of
starting and at intervals during
treatment
 Mean ratio 1.33
 >3 – suggest sample was not
at trough stage
 <0.5 suggests poor
compliance
 Clozapine levels reduced in
males, younger patients,
smokers, increased in Asians
 In non-responders, dose
should be adjusted to give
plasma level from 35-500ug/l
 Not tolerating clozapine may
benefit from a reduction to a
dose giving a plasma level
within this range
During
 FBC repeated weekly intervals
for 18 weeks (greatest risk of
neutropenia/agranulocytosis)
 Fortnightly until one year
 Monthly after 1 year of
treatment
 Dose should be slowly titrated
upwards
 Close monitoring of vitals on
initiation because of
hypotensive effect
 If not received clozapine for
48 hours or longer, should be
restarted at starting dose and
re-titrated upwards
N/A
 Lithium Clozapine
low risk of relapse = stop
drug gradually over 4
weeks, may not remove
risk of cardiac defects in
the foetus entirely.
 If not well and high risk
o Switch gradually to
antipsychotic or
o Stop Li and restart in 2nd
trimester if woman is not
planning to breastfeed and
symptoms responded
better to lithium or
o Continue with Li if high risk
 If continue Li during pregnancy
o Check serum levels every
4 weeks, weekly from 36th
week, <24hours after
childbirth
o Adjust dose to keep it at
the lower end of range
o Make sure adequate fluid
intake
o Should deliver in hospital
and be monitored during
labour (fluid balance and
levels because of risk of
dehydration and Li toxicity
in prolonged labour)
o During delivery, renal
clearance of Li falls and
may lead to toxicity in
mother and newborn – can
be stopped 24-48 hours
prior to planned delivery or
start of labour,
reintroduced 1st week
postpartum
 Breastfeeding – not advised as
excreted in breastmilk.
 However, if she strongly wishes
to breastfeed, best to advise
staying on rather than coming off
medication and relapsing
 Limited use due to 1-week  Augmentation in cases of
duration to achieve response & inadequate response to
co-administration of clozapine
antipsychotics may increase risk  Suggested options: add
Pharmacology
of neurological side effects haloperidol or amisulpride or
sulpiride or risperidone or
aripiprazole or omega-3
triglycerides
 Decreases suicidal behavior in  Response rate of 30-60% of
Benefits
people with unipolar or bipolar people with treatment
 Lithium Clozapine
disorder resistant schizophrenia
 40-70% of people with
treatment resistant
schizophrenia are also
clozapine resistant
 Reduces suicidality, hostility,
aggression and both +ve and
–ve symptoms
 Does not increase prolactin
release in humans
Early Main
 GI: vomiting, nausea, diarrhoea  Agranulocytosis (0.8%)
 Polyuria and polydipsia  Neutropenia (3%)
 Fine tremor on voluntary o Females > males
movement (propranolol may be o Older individuals
useful) >younger
 Dryness of mouth, slight thrist o Asians > Caucasians
 Fatigue, drowsiness  Sedation
 Muscle weakness  Weight gain
 Metallic taste  Constipation
At any time  Hypersalivation
 Toxicity – exacerbation of existing  Hypotension
side effects, GI, coarse tremor,  Hypertension
ataxia, incoordination, slurred  Tachycardia
speech, confusion, disorientation,  Nausea
convulsions, coma, death  Fever
 Signs evident when blood level  Seizures
>1.3mmol/l – narrow therapeutic  Exacerbates OCD symptoms
index hence need for regular Additional
Side effects monitoring  Haematological: eosinophilia,
 Anything affecting fluid balance thrombocytopenia
can ppt – dehydration, excessive  Nervous system:
sweating, vomiting, diarrhoea, dizziness.vertigo, headache,
diuretics (e.g. thiazide) tremor, syncope, delirium
 Treatment: anticonvulsants,  Cardiovascular: myocarditis,
osmotic duresis or forced alkaline cardiomyopathy
diuresis, haemodialysis  GI: transient moderate asymp.
Longer term Elevations in LFTs,
 Nephrogenic diabetes insipidus pancreatitis
 Nephropathy  GU: urinary
 Hypothyroidism (higher risk in incontinence/noctunnal
males) enuresis, urinary
 Hyperparathyroidism and urgency/frequency, urinary
hypercalcemia retention
 Oedema  Endocrine: increased risk of
 Weight gain developing hyperglycaemia
 Cardiotoxicity, arrhythmias, a/o diabetes mellitus
cardiac T wave flattening on ECG  Resp: pneumonia
 Reduced STM
Should not be given with ACEi, NSAIDs
Interaction with and diuretics – the above medications
medications can reduce renal clearance and
increase Li conc (low salt diet,
 Lithium
diarrhoea, vomiting, excessive sweating)
Anti-depressants
Selective Serotonin Reuptake
Inhibitor (SSRIs)
Tricyclic Antidepressants
(TCAs)
Drug classes
Mechanism of Action
Pharmacology
Clozapine
Anti-psychotics
First generation (typical)
 Chlorpromazine
 Promazine
 Trifluoperazine
 Fluphenazine (depot)
 Haloperidol
 Flupenthixol
 Zuclopenthixol (depot)
 Sulpiride
 Pimozide
Second generation (atypical)
 Amisupiride
 Olanzepine
 Quetiapine
 Risperidone
 Paliperidone
 Sertindole
 Clozapine
Third generation (atypical)
 Apripriprazole
 Threshold for efficacy =
>65% of D2 receptor
occupied – applies to all
antipsychotics
Effects of D2 antagonism
- Mesolimbic pathway –
antipsychotic efficacy
- Mesocortical: cognitive
function deterioration
- Nigrostriatal –
Parkinsonism and other
EPSEs
- Tuberoinfundibular
pathyway -
hyperprolactinemia
Efficacy
 Evidence based
 If differences of EPSEs
could be minimized by
careful dosing and
Anticholinergic use
avoided
 SGAs – lower
propensity for EPSEs,
higher propensity for
 Anti-depressants
Treatment
Duration of treatment
 Takes 2-4 weeks to
work
 A single episode of
depression – 6-9mo
after remission
Key points
 Risk of recurrence of
depressive illness is
high and increases with
each episode
 Those who have had
Anti-psychotics
metabolic side effects
 SGAs superior to FGAs
in treatment negative
symptoms
 Both FGA and SGA
treat positive symptoms
 FGA – important
alternative to SGA
(poorly tolerated or
preferred)
 Clozapine – superior
efficacy
 Considered an explicit
individual therapeutic
trial
 Discuss and record side
effects – most willing ot
tolerate
 Record indications and
expected benefits and
risks
 Expected time for a
change in symptoms
and side effects
 Start at lower end of
dose range and slowly
titrate upwards
 Justify and record if
outside therapeutic
range
 Record rationale for any
changes and effects
 Trials at optimum
dosage for 4-6 weeks
 Regular systematic
monitoring throughout
esp. during titration
 Assess over 2-3 weeks
1st episode – at least 2 years
At least 2 years – due to 75%
risk of relapse in someone with
schizophrenia who stops their
prescribed medication
 Discuss likely benefits
and possible side
effects of each drug
 Metabolic (weight gain,
diabetes)
 Extrapyramidal
(akathisia, dyskinesia,
dystonia)
 Cardiovascular
(prolonged QT)
 Anti-depressants Anti-psychotics
multiple episodes of  Hormonal (increase
depression – many plasma prolactin)
years treatment  Other – unpleasant
 Antidepressants: subjective experiences
effective, not addictive,  Does not cure
not known to lose schizophrenia
efficacy over time, not  Treat symptoms like
known to cause new insulin with diabetes
long term side effects  Long term treatment
 Medication needs to be required to prevent
continued at treatment relapse
dose  Family interventions and
 If S/E intolerable, CBT increase of staying
possible to find a more well (in addition to
suitable alternative biological, psychological
 If stopping medication, therapy is also
must not be done important)
suddenly as it may lead  Many antipsychotic
to unpleasant drugs are available
discontinuation effects –  Different drugs suit
needs to be reduced different patients
slowly under supervision  Perceived side effects
always discussed so
that the best tolerate
drug can be found
 Should not be stopped
suddenly
Compliance – poor compliance
a problem with schizophrenia
Factors associated with
compliance in schizo
- Attitudes
- Insight
- Side effects of meds
- Presence of negative
symptoms
- Poor psychosocial
support network
- Poor access to care

SSRIs: Depression, GAD, Typical: Schizophrenia

panic disorder, OCD, bulimia, (primarily positive symptoms),
social phobias, PTSD psychosis, acute mania,
SNRIs: depression Tourette syndrome
(Venlafaxine: GAD, panic Atypical: Schizophrenia (+ and
disorder, PTSD. Duloxetine: -), bipolar, OCD, anxiety,
Indications
diabetic peripheral neuropathy) depression, mania, Tourette
TCA: Major depression, OCD syndrome
(clomipramine), peripheral
neuropathy
(Amitriptylline)chronic pain,
migraine prophylaxis
 Anti-depressants Anti-psychotics
Anti-depressant induced 1. Sedation – greatest risk
hyponatraemia with chlorpromazine,
- HypoNa+ <135mmol/L clozapine, olanzapine
- S/E: lethargy, confusion, 2. Impaired glucose
convulsions, coma tolerance and diabetes
- Serotornergic agents – – greatest risk
most likely to cause chlorpromazine,
hypoNa clozapine, olanzapine.
- MoA : SIADH (measure OGT and
- RF: increasing age, FBG before and during)
female, renal failure, 3. Dyslipidaemia –
heart failure, hormonal increases
imbalances, circulating cardiovascular disease.
volume depletion, Greatest risk with
malignancies chlorpromazine,
- Meds that exarcebate – clozapine, olanzapine
diuretics, 4. Weight gain – clozapine
desmopression, >olanzapine >quetipaine
antiepileptics, >risperidone
antipsychotics, >amisulpride.
antidepressants, Aripiprazole – weight
anticancer – highest risk neutral
during early stages of 5. Metabolic syndrome –
Rx olanzapine
Mx: 6. Reduced seizure
- Mild hypo – fluid threshold – clozapine
restriction greatest risk
Side effects
- If symptoms, 7. HTN (clozapine) and
antidepressant QTc prolongation
discontinued (pimozide, sertindole)
- Restart – consider 8. Postural hypotension –
different class – due to a1 antagonism –
noradrenergic or MAOI increased risk when
chlorpromazine
prescribed for elderly.
Chlorpromazine,
clozapine, risperidone
and quetiapine all the
affinity a1 receptor,
dose titration necessary
9. Hyperprolactinemia –
due to dopamine
antagonism – leads to
gallactorrhoea,
amenorrhoea,
gynaecomastia,
hypogonadism, sexual
dysfunctional and
increased risk of
osteoporosis/ Most risk
with risperidone,
amisulpride, sulpride.
Add aripiprazole.
10. Anticholinergic side
 Anti-depressants Anti-psychotics
effects – dry mouth,
blurred vision,
constipation – avoid in
closed angle glaucoma
11. Photosensitivity –
chlorpromazine –
sunburn
12. Peripheral oedema –
3% with olanzapine
13. Sexual dysfunction – All
antipsychotics, all
reversible
14. Neuroleptic malignant
syndrome (NMS)

Before (baseline
investigations)
 Weight plotted on a
chart
 Waist circumference
 Pulse and BP
 Fasting blood
glucose,HbA1c, blood
lipid profile, prolactin
levels
 Ax of movement
disorder
 Ax of nutritional status,
diet and level of physical
activity
Monitoring  ECG
ECG indicated if:
 Specified in summary of
product characteristics
 Identified cardiovascular
risk (e.g. HTN)
 Personal hx of
cardiovascular disease
 Inpatient admission
During (esp during titration)
Monitor and record
 Respose to treatment –
change in symptoms
and behavior
 Side effects (take in
account overlap
 Anti-depressants Anti-psychotics
between S/E and clinical
features of
schizophrenia (e.g.
akathisia and agitation
or anxiety and impact on
functioning
 Emergence of
movement disorder
 Weight – weekly for first
6 weeks, then 12weeks,
1 year, annually)
 Waist circumference
annually
 Pulse and BP (12
weeks, 1 year, annual)
 Fasting blood glucose,
HbA1c, blood lipid levels
(12 weeks, 1 year,
annually)
 Adherence and overall
physical health
- May be able to affect
the natural course of
schizophrenia
- Repeated relapse of
Benefits illness is associated with
decline
- Prevention of relapse –
using antipsychotics –
improve outcome

SEROTONIN SYNDROME
- Life threatening condition caused by elevated serotonin conc.
- Can occur in context of initiation or dose increase of serotonergic agent, inadvertent interactions between serotonergic
medications, overdose of serotonergic medications or use of recreational drugs
- Specific agents: antidepressants, mood stabilisers, analgesics, 5-HT1 agonists (e.g. triptans), CNS stimulants,
hallucinogens, St John’s Wort
Signs/symptoms
- Psychiatric/neurological: agitation, confusion, coma, death
- Neuromuscualr: ataxia, hyperreflexia (usually lower limb), myoclonus, rigidity, tremors
- Autonomic: GI upset (nausea, diarrhoea), hyper/hypotension, hyperthermia,mydriasis, tachycardia
Comparison between serotonin syndrome and NMS
Feature Serotonin syndrome Neuroleptic malignant syndrome
Associated agent Serotonin agent Antipsychotic medication
Mechanism Serotonin excess Dopamine antagonism
Symptom onset Minutes to hours Days to weeks
Symptom resolution <24 hours 5-14 days
Muscle rigidity Less severe More severe
Activity Hyperkinesia Bradykinesia
Myoclonus and seizure Common Rare
Rhabdomyolysis Rare Common
Elevated transaminases Rare Common

Management
- Severe symptoms – immediate transfer to ED for supportive treatment and acute management
- Overdose – gastric lavage a/o activated charcoal
Biological
- Discontinue any serotonergic
- BZD – relieve muscular symptoms
- Serotonin receptor antagonists (e.g. cyprotheptadine)
 - Beta-blockers – propranolol and pindolol
Course and prognosis
- Resolve without sequelae within 24-36 hours with adequate supportive measures
- Restart serotonergic agents slowly and @ low doses and consider using serotonergic agents from a different class

TCAs SSRIs
Examples - Amitriptyline - Fluoxetine
- Nortriptyline - Paroxetine
- Imipramine - Fluvoxamine
- Trimipramine - Citalopram
- Clomipramine - Escitalopram
- Lofepramine - Sertraline
- Dothiepine
Mechanism of action Inhibits reuptake of serotonin Inhibits serotonin reuptake
and NE 5HT1a agonism (anti-
Blocks cholinergic, histaminic, pderessant, anxiolytic, anti-
alpha1 adrenergic R sites obessional, anti-bulimic effect)
Side effects - Anticholinergic - Reduced SE due to
(antimuscarinic M1) – selectivity
dry mouth, blurred - GI – nausea, vomiting
vision, drowsiness, - CNS – headache,
constipation, urinary dizziness, agitation,
retention insomnia, tremor
- Antihistamine – - Sexual dysfunction –
sedation, weight gain more likely with SSRIs
- Alpha 1 antagonism – than TCA – decrease
postural hypotension, libido, anorgasmia
sedation 5-HT2 – agitation, akathisia,
- Cardiovascular – anxiety, insomnia, sexual
arrhythmias, orthostatic dysfunction
hypotension, congestive 5-HT3 – GI upset, diarrhoea,
heart failure, headache
tachycardia, prolonged - Reduced seizure threshold –
QT, postural USE WITH CARE IN
hypotension EPILEPSY
Use in someone with Less safe Safer
cardiovascular disease or
epilepsy
Tolerability Lower Higher
Efficacy for treatment of Equal Equal
depression
Risk of interaction with alcohol Higher Lower
and other medications
Risk of developing serotonin Lower Higher
syndrome
Risk of toxicity and lethality in More dangerous Less dangerous
overdose
Impact on chronic pain Amitripyline – good effect in Little/no evidence
chronic pain without
depression
Advantages SSRIs over TCAs
- Less sedating
- No AntiAch
- Lower cardiotoxicity
- Safer in overdose
 Newer MoA Indications Main S/E
antidepressants
SNRI - Depression Nausea, dry mouth,
- GAD constipation,
dizziness, headache,
insomnia,
Venlafaxine
somnolence, sexual
dysfunction,
hypertension at higher
doses
SNRI - Depression Nausea, dry mouth,
- GAD constipation,
- Diabetic dizziness, headache,
Duloxetine neuropathy insomnia,
- Urinary stress somnolence, sexual
incontinence dysfunction,
hypertension
NARI - Depression Nausea, dry mouth,
constipation,
Reboxetine
dizziness, headache,
insomnia,
Serotonin antagonist - Depression Sedation, priapism
Trazodone and reuptake inhibitor - Anxiety
(SARI)
Tetracyclic - Depression Sedation,rash
Mianserin
antidepressant
Noradrenergic and - Depression Sedation,weight gain
Mirtazepine specific sertonoergic
antidepressant
Noradrenergic and - Depression Nausea, dry mouth,
dopaminergic reuptake - Nicotine dizziness, weight loss,
Buproprion
inhibitor dependence agitation, reduced
seizure threshold
MT1 and 2 - Depression Nausea, dizziness,
melatonergic receptor headache, insomnia,
agonist and 5-HT2c R somnolence, abdo
Agomelatine
antagonist pain, excessive
sweating, increased
LFTs
Monoamine oxidase -
inhibitors
- Phenelzine
Isocarboxazid
Tranylcypromne
Moclobemide
 MOOD Lithium
STABILISERS
Formulation Formulations
- Li carbonate (tablets)
Mechanism of - Li citrate (tablets or
action liquid)
- Treatment of mild to
moderate mania
- Prophylaxis of bipolar
affective disorder (more
effect at preventing
manic than depressive
relapse)
- Prophylaxis of recurrent
depression in people
Indications who have not responded
to standard
antidepressants, added
for augmentation
- Treatment of aggressive
behavior
- Treatment of self-
mutilating behavior
Prevention and treatment of
steroid-induced psychosis
Rx of bipolar: Prolonged
Duration of duration of due to risk of
treatment relapse following
discontinuation
Before Before
- Bloods (RFTs, TFTs),
ECG, weight, exclude
Monitoring
pregnancy
After starting or changing During
dose
Valproate Carbamezipine Lamotrigine
Formulations
- Sodium valproate - Liquid
(tablet/liquid) - Tablets – immediate or
- Valproic acid (tablet) controlled release tablets
- Semi-sodium valproate
(tablets)
- Treatment and - Treatment and - Treatment of
prophylaxis of mania prophylaxis of depressive episodes
- Treatment and depression in bipolar affective
prophylaxis of - Treatment and disorder
depression prophylaxis of mania - Prophylaxis of
- Treatment of rapid (not 1st line) bipolar affective
cycling bipolar disorder - Prophylaxis of bipolar disorder
affective disorder in
people unresponsive to
Li
- Treatment of trigeminal
neuralgia
Before Before
- Bloods (FBC, LFTs), - Bloods (FBC,RFTs, - Bloods (FBC, LFTs)
ECG, weight, exclude TFTs), ECG, weight, exclude pregnancy
pregnancy exclude pregnancy During
During - Bloods (FBC, LFTs)
- Check serum levels - Check serum
 MOOD Lithium Valproate Carbamezipine Lamotrigine
STABILISERS
- Serum Li measured every 3 months carbamazepine level
after 5 days - Check FBC, LFTs every 3 months
- Dose adjusted to every 6 months - Check FBC, RFTs and
achieve a concentration - Monitor weight LFTs every 6 months
between 0.5-1mmol/l - Monitor weight
- Bloods ideally taken 12
hours after last dose
administered
During treatment
- Check serum lithium
levels every 3 months
- RFTs and TFTs – every
9 months
- Monitor weight
- Seek attention if
symptoms of
hypothyroidism develop
e.g. lethargy and feeling
cold
If discontinued, dose should be
reduced gradually over a
period of a few weeks as
possible relapse if abruptly
discontinued
- Advice about - Increases risk of neural - Increase risk of neural - Risk of oral cleft (9
contraception tube defects (spina tube defects – risk fo in 1,000)
- Teratogen bifida & anencephaly) other major foetal - Woman taking
- Risk of foetal heart - Affects intellectual malformations – GI lamotrigine planning
Use in women defect, Ebstein’s development problems and cardiac pregnancy or
of childbearing anomaly, floppy baby - Many pregnancies are abnormalities unplanned – advise
age syndrome, potential unintended until after - Teratogen to stop due to risk of
thyroid abnormalties and 28th day (neural tube - Woman on foetal malformations
nephrogenic diabetes closes) care is needed carbamazepine planning - Alternative drug –
insipidus, miscarriage when prescribing pregnancy or unplanned antipsychotics
- Do not routinely - Should not be routinely pregnancy – advised to considered
 MOOD Lithium Valproate Carbamezipine Lamotrigine
STABILISERS
prescribed in first prescribed to women stop due to risk of NTD - Should not be
trimester or of child-bearing - Alternative drug – routinely prescribed
breastfeeding potential – if no antipsychotics for women who
- Advise woman who is effective alternative, considered pregnant because of
well and not at high risk risk of taking valproate - Should not be routinely lack evidence of
of relapse to stop drug during pregnancy and prescribed for women efficacy and risk to
o If a woman taking importance of using who pregnant because foetus
Li is pregnant – adequate of lack evidence of - Not routinely
confirmed in the contraception should efficacy and risk of NTD prescribed for
1st trimester, well be explained women
and low risk of - Should not be breastfeeding – risk
relapse = stop prescribed in women of dermatological
drug gradually <18yo – risk of PCOS problems e.g. SJS
over 4 weeks, and increased risk of
may not remove unplanned pregnancy
risk of cardiac - Women taking
defects in the valproate – planning
foetus entirely. pregnancy or is
- If not well and high risk pregnant – advise to
o Switch gradually stop taking drug
to antipsychotic - Bipolar disorder Rx –
or alternative
o Stop Li and (antipsychotic) should
restart in 2nd be considered
trimester if - If no alternative – dose
woman is not limited to max. 1g/day
planning to - Administered in divided
breastfeed and dose
symptoms - Slow release form +
responded better 5mg/day folic acid
to lithium or
o Continue with Li if
high risk
- If continue Li during
pregnancy
 MOOD Lithium Valproate Carbamezipine Lamotrigine
STABILISERS
o Check serum
levels every 4
weeks, weekly
from 36th week,
<24hours after
childbirth
o Adjust dose to
keep it at the
lower end of
range
o Make sure
adequate fluid
intake
o Should deliver in
hospital and be
monitored during
labour (fluid
balance and
levels because of
risk of
dehydration and
Li toxicity in
prolonged labour)
o During delivery,
renal clearance of
Li falls and may
lead to toxicity in
mother and
newborn – can be
stopped 24-48
hours prior to
planned delivery
or start of labour,
reintroduced 1st
week postpartum
 MOOD Lithium Valproate Carbamezipine Lamotrigine
STABILISERS
- Breastfeeding – not
advised as excreted in
breastmilk.
- However, if she strongly
wishes to breastfeed,
best to advise staying
on rather than coming
off medication and
relapsing
- Limited use due to 1-
week duration to
achieve response & co-
Pharmacology administration of
antipsychotics may
increase risk of
neurological side effects
- Decreases suicidal
behavior in people with
Benefits
unipolar or bipolar
disorder
Early - GI: gastric irritation, - GI: N&V - GI: N&V
- GI: vomiting, nausea, nausea, diarrhoea - Diplopia - Diplopia
diarrhoea - Drowsiness - Headaches - Headaches
- Polyuria and polydipsia - Weight gain - Dizziness - Dizziness
- Fine tremor on voluntary - Hyperammonaemia - Drowsiness - Rash: SJS, TEN –
movement (propranolol - Thrombocytopenia - Ataxia most rashes occur
may be useful) /agranulocytosis, Agranulocytosis (1 in in the 1st 8 weeks –
Side effects - Dryness of mouth, slight anemia 20,000) more common in ppl
thrist - Transient hair loss Avoid clozapine and with hx of allergy or
- Fatigue, drowsiness (alopecia): regrowth carbazempine together – rash from other anti-
- Muscle weakness may be curly concurrent increased risk of epileptic/mood stab.
- Metallic taste - Hepatic and pancreatic agranulocytosis – withdraw if rash
At any time toxicity/dysfunction - Thrombocytopenia develops
- Toxicity – exacerbation (rare) - Aplastic anaemia (1 in
of existing side effects, 20,000)
 MOOD Lithium Valproate Carbamezipine Lamotrigine
STABILISERS
GI, coarse tremor, - Generalised
ataxia, incoordination, erythematosus rash
slurred speech, - SJS – rare but fatal
confusion,
disorientation,
convulsions, coma,
death
- Signs evident when
blood level >1.3mmol/l –
narrow therapeutic index
hence need for regular
monitoring
- Anything affecting fluid
balance can ppt –
dehydration, excessive
sweating, vomiting,
diarrhoea, diuretics (e.g.
thiazide)
- Treatment:
anticonvulsants, osmotic
duresis or forced
alkaline diuresis,
haemodialysis
Longer term
- Nephrogenic diabetes
insipidus
- Nephropathy
- Hypothyroidism (higher
risk in males)
- Hyperparathyroidism
and hypercalcemia
- Oedema
- Weight gain
- Cardiotoxicity,
arrhythmias, cardiac T
 MOOD Lithium Valproate Carbamezipine Lamotrigine
STABILISERS
wave flattening on ECG
- Reduced STM
Should not be given with ACEi,
NSAIDs and diuretics – above
Interaction
medications reduce renal
with
clearance increase Li conc (low
medications
salt diet, diarrhoea, vomiting,
excessive sweating)