© 1998 by Oxford University Press and the Maryland Psychiatric Research Center (MPRC)
Management of the Adverse Effects of Clozapine
Psychopharmacology Fellow, Department of Psychiatry, Yale University School of Medicine, and Chief Resident of the Adult Treatment Program at the Yale-New Haven Hospital New Haven, CT
Professor of Psychiatry, Yale University School of Medicine, and the Medical Attending for the Adult Treatment Program at the Yale-New Haven Hospital New Haven, CT
Associate Professor of Psychiatry, Yale University School of Medicine, and Director of the Adult Treatment Program at the Yale-New Haven Hospital New Haven, CT
Reprint requests should be sent to Dr. C.M. Mazure, Yale-New Haven Hospital, 20th St., E.P. 10-8, New Haven, CT 06504
Clozapine has been found to be superior to traditional neuroleptics in the treatment of refractory schizophrenia and is increasingly being used to treat schizophrenia, affective disorders, some neurological disorders, and aggression. For many patients, clozapine offers new hope for the successful pharmacological management of a disabling mental disorder. However, up to 17 percent of patients must discontinue treatment with clozapine because of adverse effects, which also limit the rate at which the dose can be increased and the maximum dose that can be tolerated. This article reviews strategies for minimizing and managing the adverse effects of clozapine, including agranulocytosis, seizures, sedation, delirium, obsessive-compulsive symptoms, hypotension, tachycardia, weight gain, sialorrhea, elevated liver enzymes, constipation, nausea, enuresis, fever, and neuromuscular effects. Incidence and morbidity are presented first. Then, the known or hypothesized pathophysiology of the adverse effects are described. Finally, nonpharmacological and pharmacological interventions are reviewed. Understanding the incidence, pathophysiology, and treatments of adverse effects is essential for a positive therapeutic outcome when prescribing clozapine.
Keywords: Clozapine / atypical antipsychotics / adverse effects / side effects
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