Anti psychotic (AP)

Indication
1) Schizophrenia
2) Other psychotic disorder
3) Mood disorder with or without psychosis
4) Violent behavior
5) Autism
6) Tourette’s syndrome
7) Somatoform disorders
8) Dementia
9) OCD
 Type and mechanism
1) Typical antipsychotic medication
- blocks post synaptic dopamine receptors, treat +ve
symptoms
- e.g: Chlorpromazine, Haloperidol, Fluphenazine,
Thioridazine, and Trifluoperazine

2) Atypical antipsychotic medication

- blocks D2 and/or D1, 5-HT receptors (dopamine and
serotonin). Treats both +ve and –ve symptoms
- e.g: Clozapine (Clozaril ™), Risperidone (Risperidal™),
Quetiapine (Seroquel™), Olanzapine, and Ziprasidone
3) Dopamine system stabilizers-partial
agonist. Increase transmission of dopamine
when it is low, decrease it when it is high. E.g:
Aripiprazole.
 4) Slow release depot preparation
a) Injection IM (gluteus maximus) to patient who improve
with drugs but low compliance. - small test dose to
prevent severe/prolonged SE.
b) Esters of antipsychotic drug (oily medium)
c) Depot APs available in Malaysia are:
Fluphenazine decanoate ,Zuclopenthixol decanoate,
Flupenthixol decanoate, and Risperidone (similar
effectiveness)
d) SE: pain, edema, pruritus, palpable mass.
 Clozapine
- First atypical drug
- Binds weakly to D2 receptors and has higher affinity to
D4 receptors. It also binds to histamine H1, 5HT2,
alpha adrenergic and muscarinic receptor.
- Does not cause extrapyramidal (EPS) side effects, but it
causes neutropenia (2-3%). Regular blood test is
needed. Usually weekly for 18 weeks, and once a
month afterwards.
- Others: drowsy, sedation, hypersalivation, tachycardia,
postural hypotension, weight gain,and dizziness.
 SIDE EFFECTS of TYPICAL
ANTIPSYCHOTIC DRUGS

a) Antidopaminergic effects
b) Anti adrenergic effects
c) Others
d) Neuroleptic malignant syndrome
a) Antidopaminergic effects

3) Tardive dyskinesia
1) Acute dystonia
-Torticolllis
-Tongue protrusion
-Grimacing
-Spasm of ocular muscle
-Opisthotonus
4) Akathisia-restlessness,
agitation
2) Parkinsonism
Treatment: Antiparkinsonian agents (benztropine, amantadine, etc), benzodiazepine.
For tardive dyskinesia: discontinue offending agents, subtitute atypical medication.
Benzodiazepine, beta blockers, and cholinomimetics may be used for short term.
b) Anti adrenergic effects 5) Blurred vision
and
precipitation
of glaucoma
1) nasal congestion

2) Dry mouth 6) Postural

hypotension

3) Reduced sweating

4) Inhibition of ejaculation
7) Urinary hesitancy and retention, constipation

Treatment: As per symptoms e.g eye drops, stool softener, etc

 Other effects

1) Cardiac arrythmias 6) Accumulation of

pigment in skin, cornea
4) Galactorrhea and amenorrhea and lens

2) Hypothermia

5) Photosensitivity
7) Worsening of epilepsy

3) weight gain
 Neuroleptic malignant syndrome
• Rare
• Fluctuating loss of consciousness
• Hyperthermia
• Muscular ridgidity, increase muscle tone,
dysphagia, dyspnea
• Autonomic disturbance: unstable BP, ↑PR,
↑sweating, salivation, urinary incontinence
• Lab finding: ↑WBC and ↑creatinine
phosphokinase
Why Atypical is better than typical?

- Less side effects in extrapyramidal symptoms

and do not cause hyperprolactinemia
 Mood stabilizer
• Prevent recurrence of bipolar disorder
• Get baseline CBC, ECG, urinalysis, BUN, Cr,
electrolytes, TSH.
• Main medications:
• Lithium
• Antiepileptic drugs:
a) Sodium valproate
b) Carbamazepine
c) Lamotrigine
 Lithium
• Absorbed and excreted in kidneys.
• Therapeutic and toxic doses are close together so it is essential to monitor the
blood level. First after 4-7 days then weekly for 3 weeks, and then provided
that a satisfactory steady state has been achieved, once every 6 weeks.
• Screen for pregnancy, thyroid disease, seizure d/o, neurological, renal and CVS
disease.
• ↑ in concentration in blood
– Overdose
– Dehydration: when the proximal tubule absorbs more water, more lithium is
reabsorbed.
– ↓ Sodium: lithium is carried by the mechanism that carries sodium, and more
lithium is transported when there is less sodium.
– Thiazide therapy increase excretion of sodium but not of lithium, plasma
lithium rises.
 Side effects
• Early: polyuria, tremor, dry mouth, metallic
taste, weakness and fatigue.
• Later: fine tremor, polyuria, polydipsia, hair
loss, thyroid enlargement, hypothyroidism,
impaired concentration, weight gain, GI
distress, sedation, acne, impaired memory,
ECG changes.
• Long term : Diabetic insipidus
 Teratogenesis
• Crosses placenta, ↑rates of fetal abnormality
most affecting the heart (Ebstein’s anomaly)
• Should be avoided in first trimester of
pregnancy
• It also advisable to reduced by half or stopped
during labor to be restarted afterwards.
• It is also secreted into breastmilk so bottle-
feeding is usually advisable.
 Toxic effects
Management:
• Nausea and vomiting a) discontinue lithium for
several doses and begin
• Diarrhea again at a lower dose
when lithium has fallen
• Coarse tremor into non toxic range.
b) Monitor serum lithium
• Ataxia, dysarthria level, BUN, and
electrolytes.
• Muscle twitching, hyperreflexia c) Saline infusion, and
hemodialysis if > 2
• Confusion, coma mmol/L,coma,
• Convulsion shock,severe
dehydration, failure to
• Renal profile respond to treatment
after 24 hours, or
• Cardiovascular collapse deterioration.
 Contraindications
• Renal failure
• Recent renal disease
• Cardiac failure
• Recent myocardial infarction
• Chronic diarrhea (altered electrolytes)
 Drug interaction
1. Increased lithium concentration
• Haloperidol
• Thiazide diuretics
• Muscle relaxants
• NSAIDs
• Antibiotics eg.metronidazole & spectinomycin
• Antihypertensives eg. ACE inhibitors &
methyldopa
2. Interaction with antipsychotic
• Potentiation of extrapyramidal symptoms
• Confusion and delirium occasionally

3. Interaction with SSRIs

• 5-HT syndrome
 Management and withdrawal effects

• Usually >2 years and often much longer

• Continue medication more likely to be needed
if previously had episodes of affective d/o
within a short time, or very severe.
• Withdrawal effects: lithium should be
withdrawn gradually over a few weeks.
Sudden withdrawal may cause irritability,
emotional lability, and occasionally, relapse.
 Carbamazepine
• Effective in patient who is not responsive to
lithium, and for some rapidly recurring bipolar
disorder
• Adverse effects: if high: drowsy, dizzy, nausea,
double vision, skin rash, agranulocytosis (rare)
• Drug interaction: accelerate liver metabolism (↓
other drug effectiveness)
• Teratogenesis: safest drug to be used in
pregnancy.
 Sodium valproate
• Adverse effects: sedation, tiredness, tremor, GI
disturbance, reversible hair loss, thrombocytopenia
• Drug interaction: displaces highly protein bound
drugs such as other epileptic drugs and may
therefore increase plasma level. Lamotrigine
metabolism is inhibited so only use 50% of usual
dose.
• Teratogenesis: teratogenic and should be avoided in
pregnancy.
 Lamotrigine
• Anticonvulsants, bipolar depression, possibly
without inducing mania, and it also prevents
depressive (not mania) relapse in bipolar
disorder.
• Adverse effects: a rash (3-5%) , nausea,
headache, tremor, dizziness
• Drug interaction: increased level by valproate.
Lamotrigine+carbamazepine: neurotoxicity.
• Does not appear to be teratogenetic.
 References
• http://www.flyfishingdevon.co.uk/salmon/yea
r1/schizophrenia.htm
• http://www.yoism.org/?q=node/120
• http://www.cidpusa.org/PARKINSONS1.htm
• Gelder M, Mayou R, Geddes J. Psychiatry, 3rd
ed, Oxford University Express; 2005.