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J Clin Psychiatry. 1995 Sep;56(9):411-7.

Clozapine in severe mood disorders.

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Bipolar and Psychotic Disorders Program, Mailman Research Center, McLean Hospital, Belmont, Mass 02178, USA.



A growing literature suggests that the atypical antipsychotic agent clozapine may be effective in schizoaffective and psychotic mood disorders.


To evaluate the efficacy and tolerability of clozapine in severe mood disorders, we reviewed published studies on clozapine in schizophrenia, bipolar disorder, schizoaffective disorder, major depression, and organic disorders with psychotic or major affective syndromes, identified through the MEDLINE data base.


Patients in manic or psychotic phases of schizoaffective or bipolar disorder were significantly more likely to respond to clozapine than patients with schizophrenia (p = .006) or severe depressive syndromes (unipolar, bipolar, and schizoaffective depression combined; p = .001). There was no significant difference in the side effect profile secondary to clozapine in patients with severe mood disorders compared to patients with schizophrenia.


Clozapine appears to be effective and well-tolerated in the short-term and maintenance treatment of severe or psychotic mood disorders, particularly in the manic-excited phases of schizoaffective and bipolar disorders, even in patients who have not responded well to conventional pharmacotherapies.

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