Suicide is a major contributor to the morbidity and mortality of
schizophrenia, accounting for approximately 10% of deaths in these patients. The known risk factors for suicide in
schizophrenia include prior suicide attempts,
substance abuse, male sex, onset during first decade of illness, social isolation, depression, and feelings of hopelessness. There is significant evidence suggesting that
clozapine reduces the suicide rate in patients with
schizophrenia and
schizoaffective disorder. Possible factors that lead to a decrease in suicidality with
clozapine include the following: a direct
antidepressant action, improved cognitive function and insight, diminished negative symptoms, reduced
substance abuse, and improved compliance. These effects may converge or lessen feelings of hopelessness and more of its converse optimism. The International Suicide Prevention Trial (InterSePT) is a large prospective, 2-year randomized trial of the comparative effects of
clozapine and
olanzapine involving 980 patients at high risk for suicide in 11 countries in 56 sites. The study included complete freedom to augment these treatments if needed, blinded ratings, a blinded Suicide Monitoring Board, and equivalent clinical contact. The results support the superiority of
clozapine over
olanzapine to reduce the risk of suicidality and suggest its use should be considered for all patients with
schizophrenia with high risk for suicide.