MANAGEMENT OF THE ADVERSE-EFFECTS OF CLOZAPINE

Clozapine has been found to be superior to traditional neuroleptics in the treatment of refractory schizophrenia and is increasingly being u sed to treat schizophrenia, affective disorders, some neurological dis orders, and aggression. For many patients, clozapine offers new hope f or the successful pharmacological management of a disabling mental dis order 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 to lerated. This article reviews strategies for minimizing and managing t he adverse effects of clozapine, including agranulocytosis, seizures, sedation, delirium, obsessive-compulsive symptoms, hypotension, tachyc ardia, weight gain, sialorrhea, elevated liver enzymes, constipation, nausea, enuresis, fever, and neuromuscular effects. Incidence and morb idity are presented first. Then, the known or hypothesized pathophysio logy of the adverse effects are described. Finally, nonpharmacological and pharmacological interventions are reviewed. Understanding the inc idence, pathophysiology, and treatments of adverse effects is essentia l for a positive therapeutic outcome when prescribing clozapine.