Atypical antipsychotic drugs

The “typical” (first generation) antipsychotic drugs (such as haloperidol, chlorpromazine, and trifluoperazine) have been used to treat schizophrenia since the 1950s. The “atypical” (second generation) antipsychotics (table 1⇓) were introduced into routine practice from the 1990s. Both classes are used in the acute phase of schizophrenia and related psychoses and for long term maintenance and prevention of relapse. Typical antipsychotic drugs have a range of adverse effects, notably extrapyramidal features such as dystonia, parkinsonism, akathisia, and tardive dyskinesia. Although atypical antipsychotics are less likely to cause extrapyramidal symptoms, they may also have important adverse effects, including metabolic effects.3 Some atypical antipsychotics are also licensed to treat mood disorders, and table 1⇓ summarises licensed indications in the United Kingdom. However, this article considers their use for the treatment of non-affective psychosis only.

Antipsychotics are a pharmacologically heterogeneous group of compounds, but all act as D₂ dopamine receptor antagonists, an action linked to their antipsychotic effect.4 While the term atypical originally referred to antipsychotic drugs that did not cause catalepsy in animal models, recent academic and marketing literature uses this term to refer to both clinical properties (reduced incidence of extrapyramidal effects) and chemical properties (receptor profile).5 6 5-HT_2A antagonism and/or 5-HT_1A agonism may be …