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Cited by 1,393Schizophrenia research and treatmentSuicide and Self-Harm StudiesBipolar Disorder and Treatment

Clozapine Treatment for Suicidality in Schizophrenia<subtitle>International Suicide Prevention Trial (InterSePT)</subtitle>

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Meltzer, Herbert Y.·2003·Archives of General Psychiatry
DOI 10.1001/archpsyc.60.1.82
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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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  • Lithium and clozapine reduce risk of suicidal behavior independently of their effectiveness for mood and psychosis, indicating potential effects via the diathesis.

    “Because both medications reduce the risk of suicidal behavior independently of how effective they are for mood and psychosis (225), this indicates potential effects via the diathesis.”

    From A brain-centric model of suicidal behavior (2020) · cites this paper as [223]

  • One un-replicated RCT has shown that clozapine can reduce suicidal ideation and attempts among thought-disordered patients.

    “one un-replicated RCT has shown that clozapine can reduce suicidal ideation and attempts among thought-disordered patients [16].”

    From One Size Does Not Fit All: A Comprehensive Clinical Approach to Reducing Suicidal Ideation, Attempts, and Deaths (2019) · cites this paper as [16]

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Research works printed but not linked: 2

  1. Cohen LJ, Test MA, Brown RL. Suicide and schizophrenia: data from a prospec- tive community treatment study. Am J Psychiatry. 1990;147:602-607.
  2. Reinstein MJ, Chasonov MA, Colombo KD, Jones LE, Sonnenberg JG. Reduc- tion in suicide inpatients with schizophrenia receiving clozapine. Clin Drug Invest. 2002;22:341-346.

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Authors
Meltzer, H. Y.
Affiliations
Vanderbilt University (US)
Corresponding author
Meltzer, Herbert Y.
ORCID
Meltzer, Herbert Y.
Venue
Archives of General Psychiatry
Publisher
American Medical Association (AMA)
Published
2003-01-01
Volume
60
Issue
1
Pages
82
ISSN
0003-990X (ISSN-L)
DOI
10.1001/archpsyc.60.1.82
OpenAlex
W2166945572
Cited by
1,393
References
48
Citations by year
2026: 42 · 2025: 67 · 2024: 45 · 2023: 63 · 2022: 51 · 2021: 61 · 2020: 71 · 2019: 61 · 2018: 58 · 2017: 37 · 2016: 61 · 2015: 63 · 2014: 55 · 2013: 47 · 2012: 64
FWCI
50.19
Type
journal article
Language
en
Open access
Locations
  • Archives of General Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion)
Funders
Vanderbilt University
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Keywords
clozapine, olanzapine, schizophrenia, schizoaffective disorder, suicidality, suicide attempts, suicide prevention, antipsychotic drugs, treatment-resistant schizophrenia
MeSH terms
Olanzapine, Suicide Prevention, Adolescent, Adult, Benzodiazepines, Clozapine, Female, Humans, Male, Middle Aged, Patient Dropouts, Pirenzepine, Psychotic Disorders, Risk Factors, Schizophrenia, Schizophrenic Psychology, Severity of Illness Index, Suicide, Suicide, Attempted, Antipsychotic Agents, Treatment Outcome, Outcome Assessment, Health Care

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