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. Under-standing the incidence, pathophysiology, and treatments of adverse effects is essential for a positive therapeutic outcome when prescribing clozapine.

Clozapine is increasingly being used for clinical indications in addition to treatment-resistant schizophrenia; this article reviews the relevant literature. The first section reassesses the risks associated with clozapine treatment, particularly agranulocytosis. The next section discusses its use for schizophrenia in patients who are treatment resistant, not treatment resistant, and intolerant of traditional drug treatments. Subsequent sections address its use in mood disorders, neurologic conditions, comorbid substance abuse, aggressive behavior, and childhood schizophrenia. Each includes the initial rationale for the use of clozapine in the disorder, a critical evaluation of the relevant literature, and theories as to why clozapine's unique pharmacodynamic profile may be efficacious for the specific condition. This body of literature suggests clozapine may be an effective treatment for a wide range of disorders.

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Sir: Hallucinogen persisting perception disorder is the reexperiencing of the perceptual symptoms experienced while intoxicated with the hallucinogen. Examples of these perceptual distortions include geometric hallucinations, false perceptions of movement in the peripheral visual fields, flashes of color, positive afterimages, macropsia, and micropsia. Various pharmacologic treatments of "flashbacks," including neuroleptics and benzodiazepines, and electroconvulsive therapy have met with limited success. 1 Case report. Mr. A, a 22-year-old male college student, presented to a college counseling center with symptoms of mild depression. Six months prior to his evaluation, he had stopped using lysergic acid diethylamide (LSD), after an 8-month history of LSD abuse during which he had used between 1000 to 1800 µg at least twice a week. Despite his abstinence, he noticed the persistence of LSD-like phenomena. These phenomena included visual illusions, trailing images, depersonalization, images in his peripheral field, and visions of colorful geometric forms when he closed his eyes. They occurred almost daily, were not distressing to the patient, and had preceded the onset of his depressive symptoms. He had no history of seizures or migraines.Antidepressant treatment was begun with sertraline 25 mg and was titrated upward slowly owing to concern about these flashbacks. Mild exacerbations of these LSD-like phenomena were noted for 2 to 4 days after each dosage increase, primarily as flashes of color, positive afterimages, and fleeting hallucinations in his peripheral vision. Within 1 month after the target dose of 100 mg was reached, these perceptual disturbances decreased until they had almost completely remitted. The depressive symptoms also improved. These gains were maintained for 4 months, at which point Mr. A graduated and terminated treatment.