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 journalArticle

905 Citations (Scopus)

Abstract

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
Volume60
Issue number1
DOIs
StatePublished - Jan 1 2003

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Clozapine
Suicide
Schizophrenia
olanzapine
Therapeutics
Psychotic Disorders
Hospitalization
Attempted Suicide
Suicidal Ideation
Anti-Anxiety Agents
Random Allocation
Risk-Taking
Antidepressive Agents
Confidence Intervals

ASJC Scopus subject areas

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

Cite this

Meltzer, H. Y., Alphs, L., Green, A. I., Altamura, A. C., Anand, R., Bertoldi, A., ... Zimmerman, M. A. (2003). Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Archives of General Psychiatry, 60(1), 82-91. https://doi.org/10.1001/archpsyc.60.1.82

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

In: Archives of General Psychiatry, Vol. 60, No. 1, 01.01.2003, p. 82-91.

Research output: Contribution to journalArticle

Meltzer, HY, Alphs, L, Green, AI, Altamura, AC, Anand, R, Bertoldi, A, Bourgeois, M, Chouinard, G, Islam, MZ, Kane, J, Krishnan, R, Lindenmayer, JP, Potkin, S, Altinsan, S, Altman, S, Avigo, L, Balon, R, Benešová, V, Bengochea, L, Bitter, I, Bokowska, E, Carpiniello, B, Casey, D, Cassano, G, Chou, J, Chvila, L, Dalery, J, Delgado, P, Dell'Osso, L, Eisdorfer, C, Emsley, RA, Eng, D, Fahy, TA, Folnegovic, V, Frangou, S, Gargoloff, P, Giannelli, A, Glick, I, Greenberg, R, Grossberg, GT, Gundersen, D, Heila, H, Hsu, G, Iqbal, N, Jakovljevic, MM, Josiassen, RC, Kassaifarkas, A, Kerwin, R, Khidichian, F, Knesevich, MA, Krasuski, J, Kumar, V, Larach, VW, Lesem, M, Lewis, S, Llorca, PM, Logue, HE, Martin, S, Maurel-Raymondet, M, Mod, L, Morik, E, Morra, C, Mortimer, A, Noursalehi, M, Ostorharics-Horvath, G, Paclt, I, Pahl, JJ, Pestreich, L, Peters, JL, Pioli, R, Plopper, MG, Posever, T, Rapaport, M, Robinson, D, Robotti, CA, Rohme, H, Rouillon, F, Sack, D, Sakinsofsky, I, Seibel, P, Simpson, G, Temkin, N, Tomori, O, Vaidain, S, Vyhnándová, Z, Young, F, Zimbroff, D & Zimmerman, MA 2003, 'Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT)', Archives of General Psychiatry, vol. 60, no. 1, pp. 82-91. https://doi.org/10.1001/archpsyc.60.1.82
Meltzer, Herbert Y. ; Alphs, Larry ; Green, Alan I. ; Altamura, A. Carlo ; Anand, Ravi ; Bertoldi, Alberto ; Bourgeois, Marc ; Chouinard, Guy ; Islam, M. Zahur ; Kane, John ; Krishnan, Ranga ; Lindenmayer, J. P. ; Potkin, Steven ; Altinsan, Saide ; Altman, Siemion ; Avigo, Likiana ; Balon, Richard ; Benešová, Vanda ; Bengochea, Luis ; Bitter, Istvan ; Bokowska, Elisabeth ; Carpiniello, Bernardo ; Casey, Daniel ; Cassano, Giovanni ; Chou, James ; Chvila, Libor ; Dalery, Jean ; Delgado, Pedro ; Dell'Osso, Liliana ; Eisdorfer, Carl ; Emsley, Robin A. ; Eng, Dawn ; Fahy, Tom A. ; Folnegovic, Vera ; Frangou, Sophie ; Gargoloff, Pedro ; Giannelli, Alberto ; Glick, Ira ; Greenberg, Richard ; Grossberg, George T. ; Gundersen, Doris ; Heila, Hannale ; Hsu, George ; Iqbal, Naveed ; Jakovljevic, M. Miro ; Josiassen, Richard C. ; Kassaifarkas, Akos ; Kerwin, Rob ; Khidichian, Frederic ; Knesevich, Mary Ann ; Krasuski, Jack ; Kumar, Vinod ; Larach, Veronica Walters ; Lesem, Michael ; Lewis, Shon ; Llorca, Pierre Michel ; Logue, H. Edward ; Martin, Stephen ; Maurel-Raymondet, Muriel ; Mod, Laszlo ; Morik, Eva ; Morra, Carlos ; Mortimer, Ann ; Noursalehi, Mojtaba ; Ostorharics-Horvath, Gyorgy ; Paclt, Ivo ; Pahl, Jorg J. ; Pestreich, Linda ; Peters, Jeffrey Lee ; Pioli, Rosario ; Plopper, Michael G. ; Posever, Thomas ; Rapaport, Mark ; Robinson, Delbert ; Robotti, Carlo Andrea ; Rohme, Harry ; Rouillon, Frederic ; Sack, David ; Sakinsofsky, Isaac ; Seibel, Phillip ; Simpson, George ; Temkin, Nancy ; Tomori, Oladapo ; Vaidain, Santha ; Vyhnándová, Zdeòka ; Young, Frederick ; Zimbroff, Daniel ; Zimmerman, Marie Agathe. / Clozapine treatment for suicidality in schizophrenia : International Suicide Prevention Trial (InterSePT). In: Archives of General Psychiatry. 2003 ; Vol. 60, No. 1. pp. 82-91.
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abstract = "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.",
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TY - JOUR

T1 - Clozapine treatment for suicidality in schizophrenia

T2 - International Suicide Prevention Trial (InterSePT)

AU - Meltzer, Herbert Y.

AU - Alphs, Larry

AU - Green, Alan I.

AU - Altamura, A. Carlo

AU - Anand, Ravi

AU - Bertoldi, Alberto

AU - Bourgeois, Marc

AU - Chouinard, Guy

AU - Islam, M. Zahur

AU - Kane, John

AU - Krishnan, Ranga

AU - Lindenmayer, J. P.

AU - Potkin, Steven

AU - Altinsan, Saide

AU - Altman, Siemion

AU - Avigo, Likiana

AU - Balon, Richard

AU - Benešová, Vanda

AU - Bengochea, Luis

AU - Bitter, Istvan

AU - Bokowska, Elisabeth

AU - Carpiniello, Bernardo

AU - Casey, Daniel

AU - Cassano, Giovanni

AU - Chou, James

AU - Chvila, Libor

AU - Dalery, Jean

AU - Delgado, Pedro

AU - Dell'Osso, Liliana

AU - Eisdorfer, Carl

AU - Emsley, Robin A.

AU - Eng, Dawn

AU - Fahy, Tom A.

AU - Folnegovic, Vera

AU - Frangou, Sophie

AU - Gargoloff, Pedro

AU - Giannelli, Alberto

AU - Glick, Ira

AU - Greenberg, Richard

AU - Grossberg, George T.

AU - Gundersen, Doris

AU - Heila, Hannale

AU - Hsu, George

AU - Iqbal, Naveed

AU - Jakovljevic, M. Miro

AU - Josiassen, Richard C.

AU - Kassaifarkas, Akos

AU - Kerwin, Rob

AU - Khidichian, Frederic

AU - Knesevich, Mary Ann

AU - Krasuski, Jack

AU - Kumar, Vinod

AU - Larach, Veronica Walters

AU - Lesem, Michael

AU - Lewis, Shon

AU - Llorca, Pierre Michel

AU - Logue, H. Edward

AU - Martin, Stephen

AU - Maurel-Raymondet, Muriel

AU - Mod, Laszlo

AU - Morik, Eva

AU - Morra, Carlos

AU - Mortimer, Ann

AU - Noursalehi, Mojtaba

AU - Ostorharics-Horvath, Gyorgy

AU - Paclt, Ivo

AU - Pahl, Jorg J.

AU - Pestreich, Linda

AU - Peters, Jeffrey Lee

AU - Pioli, Rosario

AU - Plopper, Michael G.

AU - Posever, Thomas

AU - Rapaport, Mark

AU - Robinson, Delbert

AU - Robotti, Carlo Andrea

AU - Rohme, Harry

AU - Rouillon, Frederic

AU - Sack, David

AU - Sakinsofsky, Isaac

AU - Seibel, Phillip

AU - Simpson, George

AU - Temkin, Nancy

AU - Tomori, Oladapo

AU - Vaidain, Santha

AU - Vyhnándová, Zdeòka

AU - Young, Frederick

AU - Zimbroff, Daniel

AU - Zimmerman, Marie Agathe

PY - 2003/1/1

Y1 - 2003/1/1

N2 - 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.

AB - 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.

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