The Pharmaceutical Journal
Vol 270 No 7232 p72
18 January 2003

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Clozapine reduces suicidal behaviour in patients with schizophrenia

Suicidal behaviour among patients with schizophrenia can be reduced with clozapine (Clozaril) treatment, a new study suggests.

The international suicide prevention trial (InterSePT) involved 980 patients with schizophrenia or schizoaffective disorder who were judged to be at high risk of suicide. They were randomly assigned to open-label treatment with either clozapine or olanzapine (Zyprexa) and followed up for two years.

Suicide attempts were identified by the study investigators and then reviewed by an independent, blinded suicide monitoring board. Rescue interventions to prevent suicide were analysed as secondary end-points. Olanzapine was considered to be a suitable comparator drug because there is some evidence that it, too, may reduce suicide attempts among patients with schizophrenia.

The investigators found that patients treated with clozapine attempted suicide less frequently than those treated with olanzapine (see Panel). There was also a delay in the time taken to attempt suicide for these patients. Professor Robert Kerwin, lead study investigator for the United Kingdom and professor of clinical neuropharmacology at the Institute of Psychiatry, King's College London, said: "We already knew that clozapine could help people with schizophrenia. Now it is apparent that the Government's suicide reduction target could be reached more quickly if these study data lead to the wider use of clozapine in people with schizophrenia at high risk of suicide."

Presenting the results, Professor Kerwin explained that the two drugs were broadly similar as antipsychotic agents. "The suicide effect is therefore not a secondary effect due to one drug being a better antipsychotic," he said.

The researchers comment that clozapine treatment requires extra clinical contact (due to white blood cell count monitoring) that is likely to reduce the risk of suicide. However, they point out that equivalent clinical contact given in the study to patients treated with olanzapine demonstrates that increased contact alone cannot account for clozapine's effect.

"Mechanisms that have been suggested for the effect of clozapine include an intrinsic antidepressant activity, as also suggested by effects on mood symptoms and the differential antidepressant drug use in this study," they say. The study, funded by Novartis, is published in Archives of General Psychiatry (2003;60:82) .

David Taylor, chief pharmacist at the Maudsley Hospital, London, commented: "The National Institute for Clinical Excellence has recognised the benefits of clozapine in the treatment of refractory schizophrenia by recommending a three-fold increase in its use. The results of this study provide another compelling reason for the earlier, more widespread use of clozapine."

A spokeswoman for Lilly, manufacturer of Zyprexa, said the company was pleased with the study results, which had confirmed that both drugs were equally effective as antipsychotics. She added that the investigators had acknowledged that olanzapine also reduced the risk of suicidal behaviour in high-risk patients and pointed out that the number of completed suicides was actually lower among patients treated with olanzapine.