InterSePT

Population

• 980 patients with schizophrenia or schizoaffective disorder at high risk for suicide because of previous suicide attempts or current suicidal ideation; 26.8% were refractory to previous treatment.

Intervention

Clozapine. After randomization, unmasked clinicians could make any interventions necessary to prevent suicide attempts.

Comparator

Olanzapine, with the same visit schedule to equalize clinical contact.

Key results

• Suicidal behavior was lower with clozapine than olanzapine (HR 0.76, 95% CI 0.58-0.97; P=0.03).
• Fewer clozapine-treated patients attempted suicide (34 vs 55; P=0.03), required hospitalizations to prevent suicide (82 vs 107; P=0.05), or required rescue interventions to prevent suicide (118 vs 155; P=0.01).
• Fewer clozapine-treated patients required concomitant antidepressants (221 vs 258; P=0.01) or anxiolytics or soporifics (301 vs 331; P=0.03).
• Few patients died of suicide (5 with clozapine vs 3 with olanzapine; P=0.73).

Harms

• Death from suicide did not differ (5 clozapine vs 3 olanzapine; P=0.73).
• The abstract does not report agranulocytosis, metabolic, or other drug-specific adverse-event rates.

Practice impact

• In schizophrenia or schizoaffective disorder with prior attempts or current suicidal ideation, use clozapine rather than olanzapine when the goal is fewer suicide attempts and suicide-related hospitalizations.

Applicability

• Most applicable to patients with schizophrenia or schizoaffective disorder at high suicide risk, including a minority (26.8%) refractory to previous treatment, followed for 2 years.

Limitations

• Clinicians were unmasked and could intervene to prevent suicide; only end-point raters, including an independent suicide monitoring board, were masked.
• Completed suicide was rare, so the trial was not informative for death from suicide.
• The abstract does not report clozapine-specific laboratory or metabolic harms.

Common misinterpretations

• InterSePT did not show fewer completed suicides; deaths were 5 vs 3 (P=0.73).
• This is clozapine versus olanzapine in a high-risk sample, not clozapine versus all antipsychotics or versus usual community care.