 Also known as neuroleptics/ major tranquillisers

 Antipsychotics are used to reduce the psychotic

symptoms in conditions including
 Schizophrenia
 Bipolar disorder (mania)
 Delirium
 Psychosis due to other causes e.g. drug-induced
psychosis
 Reserpine and chlorpromazine are first
medications to reduce the psychotic symptoms in
schizophrenia
 Classical (typical) antipsychotics – D2
antagonist
 Phenothiazines: chlorpromazine, thioridazine,
trifluoperazine, etc.
 Butyrophenones: haloperidol, benperidol, etc.
 Thioxanthenes : flupentixol, zuclopentixol
 Others: pimozide, loxapine
 Atypical antipsychotics – heterogeneous in
receptor binding properties
 Clozapine, olanzapine, risperidone, apriprazole,
amisulpride, quetiapine, etc.
 Typical antipsychotics act by predominantly
blocking D2 receptor
 Atypical antipsychotics act by modulation
multiple receptors
 Greater antagonism of 5HT2 receptors than of D2
receptors
 Has low affinity for D2 receptors and high affinity
for D4 receptors
 Antipsychotics are well absorbed after oral
administration
 Widely distributed and metabolised by CYP450
 Depot IM injections also available release drug
over 2-4 weeks
 Haloperidol
 Flupentixol
 Fluphenazine
 Zuclopenthixol
 Pipothiazine
 Olanzapine
 Risperidone
Classical antipsychotics
 Acute neurologic effects
 Acute dystonia
 Akanthisia
 Parkonsonism
 Chronic neurological effects
 Tardive dyskinesia
 Neuroendocrine
 Amenorrhoea
 Galactorrhoea
 Infertility
 Idiosynchratic
 Neuroleptic malignant syndrome (less common
with atypical antipsychotics)
 Antihistaminergic
 Sedation
 Anticholinergic
 Dry mouth
 Blurred vision
 Constipation
 Urinary retention
 Ejaculatory failure
 Antiadrenergic
 Hypotension
 Arrhythmia
 Others
 Weight gain
 Seizures
 Interference with temperature regulation
 Photosensitivity
 Cholestatic jaundice
 Retinal pigmentation, etc.
Atypical antipsychotics
 Similar AE can be produced but of lesser
degree
 Extrapyramidal effects are less likely
 Clozapine has the risk of agranulocytosis and
also may cause postural hypotension and
tachycardia
 Occurs in 1% of patients esp. with high doses
 Increased risk in
 Elderly
 Organic brain disease
 Hyperthyroidism
 Dehydration
 Concomitant use of SSRI or TCA
 Clinical features
 Fever
 Confusion
 Muscle rigidity
 Autonomic instability
▪ Labile BP
▪ Urinary incontinence or retention
 Raised plasma CPK
 Treatment
 Discontinue the antipsychotic
 Rehydration and body cooling
 BZD to calm the patient
 DA agonist may b useful in some cases
 Carries mortality rate of 12-15% due to
 Arrhythmia
 Rhabdomyolysis
 Respiratory failure
 Antipsychotics are used to treat psychotic
illnesses including schizophrenia and
psychosis associated with depression and
mania
 Acute treatment of psychosis
 Prophylaxis of psychosis
 Others
 Tic disorder/ Tourette's syndrome
 Recurrent self-harming
 Aetiology is unknown but, likely to be
multifactorial
 Has strong genetic component
 Clinical presentation characterized by
 Positive symptoms
 Negative symptoms
 Cognitive impairment
 Characteristically develop in people aged 15-
45 years
 Considered as neurodevelopmental disorder
 Hypothesis of schizophrenia
 Dopaminergic dysfunction
▪ Positive symptoms are more closely associated with DA
receptor hyperactivity
▪ Negative symptoms and cognitive impairment are
closely related to DA receptor hypoactivity
 5HT also seems to play a major role
 Defect in NMDA glutamate receptor function
 Selection based on
 Degree of sedation required
 Patients’ susceptibility to extrapyramidal side effect
 Patients response to the drug
 Tolerance to the secondary effects
 Chlorpromazine, still widely used despite of wide
range of AE; has marked sedative effect, useful
for violent patient
 Clozapine is effective against negative symptoms
and resistant cases
 Starting at low doses for “neuroleptic neive’
 Titrated over 4-6 weeks
 Depot preparations are used for patients with
poor compliance
 Clozapine must be initiated under specialist
supervision
 Monitoring of leukocyte count and BP
 Rapid tranquilization for severely disturbed or
violent patients
 Usually haloperidol, olanzapine or risperidone
with or without BZD
 Withdrawal of antipsychotics must be
gradually withdrawn
 Atypical antipsychotics
 have less effect on D2 receptors
 act on multiple receptors
 have lesser AE than typical ones esp.
extrapyramidal and hyperprolactinemia
 have greater efficacy against negative symptoms
 more effective against treatment resistant cases
 FBC, blood urea and electrolytes and LFT
before starting treatment and then annually
 Lipid profile and BW – baseline, after 3
months and then yearly
 FBS baseline, after 4-6 months and then
yearly
 BP – before staring and at follow-up visits and
more frequently during dose change
 Recommended to have physical health
monitoring at least once a year
 Monitor for symptoms of hyperprolactinemia
 Patients with H/O CV diseases or CV risk
factors – ECG before staring treatment
 Clozapine requires monitoring of WBC and
DC
 Weekly for first 18 weeks
 Then every 2 weeks up to 1 year
 Thereafter monthly
 Elderly
 Should NOT be used for mild – moderate psychotic
symptoms
 Starting dose must be smaller than adults dose
 Regular review of treatment
 Patients with learning disabilities
 Dose reduction or discontinuation of long-term
treatment followed by review of patient’s condition
 Referral to psychiatrist experienced in dealing with
patients with learning disabilities is recommended
 Pregnancy and breast-feeding
 Medications based on foetal impact (particularly in T1)
and mental health of the mother as they are designed
to cross BBB, they can pass through placenta
 Extrapyramidal and withdrawal symptoms are reported
in neonates occasionally in maternal use of
antipsychotics in T3; these neonates should be
monitored for the above symptoms
 During breast-feeding chronic use should be avoided
unless absolutely necessary