Clozapine Reduces Suicide Attempts in Schizophrenic Patients

Laurie Barclay, MD

January 16, 2003

Jan. 16, 2003 — Clozapine (Clozaril) reduces suicide attempts in patients with schizophrenia and schizoaffective disorder, according to the results of a multicenter randomized trial published in the January issue of the Archives of General Psychiatry. The investigators report that this is the first time that pharmacologic therapy has been demonstrated to reduce suicidal behavior.

"The risk of suicide attempts in people with schizophrenia — and especially schizoaffective disorder — is appallingly high," lead author Herbert Y. Meltzer, MD, from Vanderbilt University in Nashville, Tennessee, says in a news release. "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 International Suicide Prevention Trial (InterSePT) compared the risk of suicidal behavior in 980 patients with schizophrenia or schizoaffective disorder treated with clozapine or olanzapine (Zyprexa). All subjects were considered at high risk for suicide because of previous suicide attempts or current suicidal ideation, and 26.8% were refractory to previous treatment. During the study, all patients were seen weekly for six months and then biweekly for 18 months. After randomization, unmasked clinicians made any interventions needed to prevent suicide attempts.

Suicidal behavior assessed by masked raters, including suicide attempts, actual suicides, hospitalizations to prevent suicide, and ratings of "much worsening of suicidality" from baseline, was significantly less in the clozapine group than in the olanzapine group (hazard ratio, 0.76; 95% confidence interval, 0.58 - 0.97; P = .03). During the study, five patients receiving clozapine and three patients receiving olanzapine died of suicide (P = .73).

Compared with the olanzapine group, the clozapine group did better in terms of suicide attempts (34 vs. 55; P = .03), required hospitalizations (82 vs. 107; P = .05), or rescue interventions (118 vs. 155; P = .01) to prevent suicide, or need for concurrent treatment with antidepressants (221 vs. 258; P = .01), or anxiolytics or soporifics (301 vs. 331; P = .03).

"Overall, this study demonstrated that Clozaril is superior to Zyprexa for the prevention of suicide attempts in patients with schizophrenia and schizoaffective disorder who are at risk for suicide," Meltzer says. "Wider use of Clozaril in this population could very well help to save many lives each year. I think that InterSePT will fundamentally change the care that suicidal patients with psychosis receive in the future."

Coauthor John M. Kane, from the North Shore Long Island Jewish Health System in New York, offered a number-needed-to-treat analysis: "Over a two-year period, if we treat 13 at-risk patients with Clozaril instead of Zyprexa, we would prevent one suicide attempt or one hospitalization to prevent suicide."

Novartis Pharmaceuticals Corporation sponsored this study and has financial arrangements with some of its authors.

Arch Gen Psychiatry. 2003;60:82-91

Reviewed by Gary D. Vogin, MD

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