Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT)

Herbert Y. Meltzer, Larry Alphs, Alan I. Green, A. Carlo Altamura, Ravi Anand, Alberto Bertoldi, Marc Bourgeois, Guy Chouinard, M. Zahur Islam, John Kane, Ranga Krishnan, J. P. Lindenmayer, Steven Potkin, Saide Altinsan, Siemion Altman, Likiana Avigo, Richard Balon, Vanda Benešová, Luis Bengochea, Istvan BitterElisabeth Bokowska, Bernardo Carpiniello, Daniel Casey, Giovanni Cassano, James Chou, Libor Chvila, Jean Dalery, Pedro Delgado, Liliana Dell'Osso, Carl Eisdorfer, Robin A. Emsley, Dawn Eng, Tom A. Fahy, Vera Folnegovic, Sophie Frangou, Pedro Gargoloff, Alberto Giannelli, Ira Glick, Richard Greenberg, George T. Grossberg, Doris Gundersen, Hannale Heila, George Hsu, Naveed Iqbal, M. Miro Jakovljevic, Richard C. Josiassen, Akos Kassaifarkas, Rob Kerwin, Frederic Khidichian, Mary Ann Knesevich, Jack Krasuski, Vinod Kumar, Veronica Walters Larach, Michael Lesem, Shon Lewis, Pierre Michel Llorca, H. Edward Logue, Stephen Martin, Muriel Maurel-Raymondet, Laszlo Mod, Eva Morik, Carlos Morra, Ann Mortimer, Mojtaba Noursalehi, Gyorgy Ostorharics-Horvath, Ivo Paclt, Jorg J. Pahl, Linda Pestreich, Jeffrey Lee Peters, Rosario Pioli, Michael G. Plopper, Thomas Posever, Mark Rapaport, Delbert Robinson, Carlo Andrea Robotti, Harry Rohme, Frederic Rouillon, David Sack, Isaac Sakinsofsky, Phillip Seibel, George Simpson, Nancy Temkin, Oladapo Tomori, Santha Vaidain, Zdeòka Vyhnándová, Frederick Young, Daniel Zimbroff, Marie Agathe Zimmerman

Research output: Contribution to journalArticlepeer-review

1158 Citations (Scopus)


Background: Approximately 50% of patients with schizophrenia or schizoaffective disorder attempt suicide, and approximately 10% die of suicide. Study results suggest that clozapine therapy significantly reduces suicidal behavior in these patients. Methods: A multicenter, randomized, international, 2-year study comparing the risk for suicidal behavior in patients treated with clozapine vs olanzapine was conducted in 980 patients with schizophrenia or schizoaffective disorder, 26.8% of whom were refractory to previous treatment, who were considered at high risk for suicide because of previous suicide attempts or current suicidal ideation. To equalize clinical contact across treatments, all patients were seen weekly for 6 months and then biweekly for 18 months. Subsequent to randomization, unmasked clinicians at each site could make any interventions necessary to prevent the occurrence of suicide attempts. Suicidal behavior was assessed at each visit. Primary end points included suicide attempts (including those that led to death), hospitalizations to prevent suicide, and a rating of "much worsening of suicidality" from baseline. Masked raters, including an independent suicide monitoring board, determined when end point criteria were achieved. Results: Suicidal behavior was significantly less in patients treated with clozapine vs olanzapine (hazard ratio, 0.76; 95% confidence interval, 0.58-0.97; P = .03). Fewer clozapine-treated patients attempted suicide (34 vs 55; P = .03), required hospitalizations (82 vs 107; P = .05) or rescue interventions (118 vs 155; P = .01) to prevent suicide, or required concomitant treatment with antidepressants (221 vs 258; P = .01) or anxiolytics or soporifics (301 vs 331; P = .03). Overall, few of these high-risk patients died of suicide during the study (5 clozapine vs 3 olanzapine-treated patients; P = .73). Conclusions: Clozapine therapy demonstrated superiority to olanzapine therapy in preventing suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide. Use of clozapine in this population should lead to a significant reduction in suicidal behavior.

Original languageEnglish
Pages (from-to)82-91
Number of pages10
JournalArchives of General Psychiatry
Issue number1
Publication statusPublished - 1 Jan 2003

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health


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