Suicidality in schizophrenia: a review of the evidence for risk factors and treatment options.

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.