Expansion
Extrapyramidal effects with typicals, metabolic effects with atypicals
Expansion
Typical (first generation): haloperidol, chlorpromazine. Dominated by D2 blockade
- Extrapyramidal effects in a characteristic time sequence:
- Acute dystonia: hours to days
- Akathisia: days to weeks
- Parkinsonism: weeks to months
- Tardive dyskinesia: months to years, often irreversible
- Hyperprolactinaemia: galactorrhoea, amenorrhoea, gynaecomastia
- QT prolongation, sedation, antimuscarinic effects
Atypical (second generation): olanzapine, risperidone, quetiapine, aripiprazole
- Fewer extrapyramidal effects but prominent metabolic effects: weight gain, diabetes, dyslipidaemia
- Risperidone still raises prolactin markedly
Clozapine is unique: reserved for treatment-resistant schizophrenia, with the best efficacy but requiring registration and monitoring for agranulocytosis, myocarditis, severe constipation and ileus, and seizures. Smoking induces its metabolism, so stopping smoking raises levels dangerously.
Neuroleptic malignant syndrome: fever, rigidity, autonomic instability, raised creatine kinase, developing over days. Treated by stopping the drug, cooling, and dantrolene or bromocriptine.