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

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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  • Authors+Show Affiliations

    ,

    Psychiatric Hospital at Vanderbilt, 1601 23rd Ave S, Suite 306, Nashville, TN 37212, USA. herbert.meltzer@mcmail.vanderbilt.edu

    , , , , , , , , , , , ,

    Source

    Archives of general psychiatry 60:1 2003 Jan pg 82-91

    MeSH

    Adolescent
    Adult
    Antipsychotic Agents
    Benzodiazepines
    Clozapine
    Female
    Humans
    Male
    Middle Aged
    Olanzapine
    Outcome Assessment (Health Care)
    Patient Dropouts
    Pirenzepine
    Psychotic Disorders
    Risk Factors
    Schizophrenia
    Schizophrenic Psychology
    Severity of Illness Index
    Suicide
    Suicide, Attempted
    Treatment Outcome

    Pub Type(s)

    Clinical Trial
    Comparative Study
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    12511175

    Citation

    Meltzer, Herbert Y., et al. "Clozapine Treatment for Suicidality in Schizophrenia: International Suicide Prevention Trial (InterSePT)." Archives of General Psychiatry, vol. 60, no. 1, 2003, pp. 82-91.
    Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry. 2003;60(1):82-91.
    Meltzer, H. Y., Alphs, L., Green, A. I., Altamura, A. C., Anand, R., Bertoldi, A., ... Potkin, S. (2003). Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Archives of General Psychiatry, 60(1), pp. 82-91.
    Meltzer HY, et al. Clozapine Treatment for Suicidality in Schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry. 2003;60(1):82-91. PubMed PMID: 12511175.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Clozapine treatment for suicidality in schizophrenia: 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 - ,, PY - 2003/1/7/pubmed PY - 2003/1/24/medline PY - 2003/1/7/entrez SP - 82 EP - 91 JF - Archives of general psychiatry JO - Arch. Gen. Psychiatry VL - 60 IS - 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. SN - 0003-990X UR - https://www.unboundmedicine.com/medline/citation/12511175/full_citation L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=12511175.ui DB - PRIME DP - Unbound Medicine ER -