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Effects of Newer Antipsychotics on Extrapyramidal Function


Following acceptance of clozapine as a superior antipsychotic agent with low risk of adverse extrapyramidal syndromes (EPS), such as dystonia, parkinsonism, akathisia or tardive dyskinesia, several novel antipsychotic drugs have been developed with properties modelled on those of clozapine. Though generally considered ‘atypical’ in their relatively low risk of inducing EPS, these agents vary considerably in their pharmacology and impact on neurological functioning.

Although few comparative data are available, the atypical antipsychotics can be tentatively ranked by EPS risk (excluding akathisia and neuroleptic malignant syndrome) in the following order: clozapine < quetiapine < olanzapine = ziprasidone. At higher doses, risperidone is ranked with a higher EPS risk than olanzapine and ziprasidone, but its risk of EPS is lower with lower doses. In general, this ranking is inversely related to antidopaminergic (D2 receptor) potency. The high antiserotonergic (5-HT2A receptor) potency of risperidone, clozapine, ziprasidone and olanzapine, but not quetiapine, as well as the anti-muscarinic activity of olanzapine and clozapine may also limit EPS.

For the treatment of psychotic reactions to dopamine agonist therapy in Parkinson’s disease, clozapine is both effective and relatively well tolerated; quetiapine may be tolerated, olanzapine is not well tolerated, risperidone is poorly tolerated, and amisulpride and ziprasidone have not been well evaluated. Clozapine, perhaps because of its anticholinergic activity, can reduce parkinsonian tremor. It is useful for ongoing psychosis with tardive dyskinesia, especially for dystonic features. No atypical antipsychotic is clearly effective for motor abnormalities in Huntington’s disease or Tourette’s syndrome, and the effect of these drugs on other neurological disorders have been well evaluated in only small numbers of patients.

In summary, with the exception of clozapine, and perhaps quetiapine, atypical antipsychotics have brought only relative avoidance of EPS, strongly encouraging continued searches for novel antipsychotic agents.

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Supported, in part, by NIH grant MH-47370, a grant from the Bruce J. Anderson Foundation, by the McLean Hospital Private Donors Neuropharmacology Research Fund and by an investigator-initiated research award from Eli Lilly Corporation (RJ Baldessarini), NARSAD Young Investigator award, Theodore and Vada Stanley Foundation (FI Tarazi).

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Correspondence to Dr Daniel Tarsy.

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Tarsy, D., Baldessarini, R.J. & Tarazi, F.I. Effects of Newer Antipsychotics on Extrapyramidal Function. Mol Diag Ther 16, 23–45 (2002).

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  • Clozapine
  • Risperidone
  • Olanzapine
  • Quetiapine
  • Atypical Antipsychotic