Herbert Meltzer, M.D., lead author of the study, said “The risk of suicide attempts in people with schizophrenia-- and especially schizoaffective disorder-- is appallingly high. About 30 to 40 percent will make a suicide attempt during their lifetime, and 10 percent of people with schizophrenia will actually die from suicide. The risk is especially high for males in the first decade of their illness and is further exacerbated by substance abuse, which is present in about 50 percent of people with schizophrenia in the United States.”

The International Suicide Prevention Trial began in 1998 as a randomized study to compare clozapine and olanzapine in reducing the risk of suicide and self-destructive behavior in patients with schizophrenia or schizoaffective disorder. Nearly 1,000 people participated in the study at centers in the Americas, Europe, and the Middle East.

One powerful aspect of the study design combined un-blinded psychiatrists with blinded raters. With this design, investigators knew which medication their patients received and were able to make any interventions necessary to prevent suicide attempts. Changes in suicide risk were assessed with the Clinical Global Impression of Suicide Severity scale and a semi-structured interview, both of which were administered by blinded raters. All patients were assessed at baseline and at 8-week intervals throughout the trial. All deaths, suicide attempts, and hospitalizations to prevent suicide were reviewed by a blinded expert board that identified study endpoints.

Data show that the risk for a suicide attempt or hospitalization to prevent suicide was significantly lower in patients treated with clozapine compared with those treated with olanzapine. In addition, patients treated with clozapine made fewer suicide attempts, required fewer rescue interventions and hospitalizations, and needed fewer add-on medications such as antidepressants and anxiolytics.

The most common adverse events associated with clozapine use were salivary hypersecretion, somnolence, dizziness, and constipation, which is consistent with current prescribing information.

The authors hope that the trial findings translate into more effective care for suicidal patients with schizophrenia or schizoaffective disorder and fewer deaths due to suicide.