The Pharmaceutical Journal
Vol 270 No 7249 p675
17 May 2003

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Side effect benefits queried for newer antipsychotics

The side effect profile of new generation atypical antipsychotics may not be as much of an improvement over conventional antipsychotic drugs as previously thought.

Dr Stefan Leucht, Zucker Hillside Hospital, New York, and colleagues point out that previous reviews of trials have shown newer drugs to be associated with a low risk of extrapyramidal side effects.

“However, this finding was biased by the widespread use of high doses of comparator drugs, mainly haloperidol, which have a high risk of extrapyramidal side effects,” they say.

The researchers reviewed 31 randomised controlled trials in which new generation antipsychotics had been compared with low-potency conventional drugs, mainly chlorpromazine. The atypical antipsychotics included amisulpride (Solian), clozapine (Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), sertindole (Serdolect) and zotepine (Zoleptil).

They found that, of the new generation drugs, only clozapine was associated with fewer extrapyramidal side effects and higher efficacy than low-potency conventional drugs. Less robust evidence pointed to a similar result for olanzapine.

“This result is important because a low risk of extrapyramidal side effects is thought to be the main advantage of an atypical antipsychotic,” they say.

The researchers acknowledge that there are limitations to their analysis and say they cannot make treatment recommendations. However, they suggest that trials to establish appropriate doses of low-potency antipsychotics might show that some conventional drugs, used in appropriate doses, have properties similar to those of atypical drugs. “This finding would be important for patients with schizophrenia in settings where new generation drugs are not generally affordable,” they say.
The study is published in The Lancet (2003;361:1581).