Expansion
Typicals cause movement problems, atypicals cause metabolic ones
Expansion
- Typical (first generation): haloperidol, chlorpromazine, flupentixol. Predominantly D2 blockade, so extrapyramidal side effects and hyperprolactinaemia
- Atypical (second generation): olanzapine, quetiapine, risperidone, aripiprazole, clozapine. Broader receptor activity, so fewer movement problems but more metabolic effects
“Typicals move you, atypicals fatten you.”
Extrapyramidal side effects, in order of appearance:
- Acute dystonia, within hours to days. Treat with procyclidine
- Akathisia, an inner restlessness, within days to weeks
- Parkinsonism, within weeks to months
- Tardive dyskinesia, after months to years, often irreversible
Metabolic effects, worst with olanzapine and clozapine: weight gain, dyslipidaemia, type 2 diabetes. Monitor weight, glucose or HbA1c, and lipids.
Clozapine is uniquely effective in treatment resistant schizophrenia but carries:
- Agranulocytosis, requiring mandatory full blood count monitoring
- Myocarditis and cardiomyopathy, early
- Severe constipation and ileus, which has caused deaths
- Seizures, hypersalivation, and loss of efficacy after 48 hours of missed doses, requiring retitration
All antipsychotics prolong the QT and increase stroke and mortality risk in elderly patients with dementia.