Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT).
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.
Meltzer
Herbert Y
HY
Psychiatric Hospital at Vanderbilt, 1601 23rd Ave S, Suite 306, Nashville, TN 37212, USA. herbert.meltzer@mcmail.vanderbilt.edu
Alphs
Larry
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Green
Alan I
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Altamura
A Carlo
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Anand
Ravi
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Bertoldi
Alberto
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Bourgeois
Marc
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Chouinard
Guy
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Islam
M Zahur
MZ
Kane
John
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Krishnan
Ranga
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Lindenmayer
J P
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Potkin
Steven
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D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines; D003024:Clozapine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D017063:Outcome Assessment, Health Care; D010352:Patient Dropouts; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D013405:Suicide / Q000523:psychology; D013406:Suicide, Attempted / Q000517:prevention & control / Q000523:psychology; D016896:Treatment Outcome; D000092864:Suicide Prevention
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D003024:Clozapine; D000077152:Olanzapine