These data indicate that N-methyl-D-aspartate antagonists produce a broad range of symptoms, behaviors, and cognitive deficits that resemble aspects of endogenous psychoses, particularly schizophrenia and dissociative states.

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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.

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The concept of insight as it applies to patients suffering from psychotic illness is reviewed. An exploratory study using structured interviews with patients recovering from psychotic illness indicated that the characteristics of insight fell into five main dimensions: (1) views about symptoms, (2) views about the existence of an illness, (3) speculations about etiology, (4) views about vulnerability to recurrence, and (5) opinions about the value of treatment. Some preliminary findings regarding the association of patterns of insight with diagnosis and chronicity of illness, and the implications of these findings for clinical work and for future research, are presented.

When fixed doses of haloperidol or perphenazine were used in two separate studies, we found that psychotic males with a prior history of psychotogenic drug use had a poorer early neuroleptic response even in the early stages of their psychotic disorder than psychotic males who had not previously used significant amounts of psychotogenic drugs. Relative neuroleptic refractoriness may be characteristic of some dual diagnosis patients at the beginning of their illness. Antecedent psychotogenic drug use may contribute to the development of psychosis and to relative neuroleptic refractoriness by means of effects upon dopaminergic mechanisms.