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Am Fam Physician. 1998;57(1):142-144

In the treatment of patients with schizophrenia, use of antipsychotic agents leads to fewer delusions, fewer hospitalizations and more self-reliance. However, the adverse effects of these antipsychotic agents temper complete enthusiasm for them. Newer antipsychotics, such as clozapine, may represent an advance since they have atypical pharmacologic features. Small and associates conducted a double-blind, placebo-controlled trial of quetiapine fumarate, a dibenzothiazepine antipsychotic drug that acts at multiple receptor sites, to determine its efficacy in the treatment of patients with schizophrenia.

Hospitalized adult patients with Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria for acute exacerbation of chronic or subchronic schizophrenia were included in the study if they had no concomitant condition, such as mental retardation, and if they had not received injectable long-acting antipsychotic agents in the previous month. All psychotropic medications were discontinued, and patients were randomized to receive one of three treatment regimens: quetiapine in high dosages (up to 750 mg per day), quetiapine in low dosages (up to 250 mg per day) or placebo. The daily dosage was increased within the prescribed range until an adequate therapeutic effect was achieved. Extrapyramidal effects were evaluated and treated, if necessary. Symptoms of schizophrenia were assessed at baseline and weekly for six weeks. Adverse effects were assessed for severity and recorded.

A total of 96 patients were included in the placebo group, 94 patients were included in the low-dose quetiapine group and 96 patients were included in the high-dose quetiapine group. At least one half of the patients in each group withdrew before the end of the six-week study period, primarily because of treatment failure. At baseline, mean scores on the Brief Psychiatric Rating Scale (BPRS) were similar among the three groups. Patients in the high-dose group consistently showed improvements in BPRS scores compared with patients in the low-dose and placebo groups. Quetiapine was consistently effective in decreasing positive symptoms of schizophrenia. Mean Clinical Global Impression Severity of Illness scores were also significantly better (lower) in the high-dose group compared with the other two groups.

The patients taking high doses of quetiapine and the patients taking placebo received more treatment for extrapyramidal signs than did patients taking low doses of quetiapine. Agitation and somnolence were the most common adverse effects. Akathisia was most common in the patients receiving higher doses of quetiapine. Seventeen patients (seven in the high-dose group, seven in the low-dose group and three in the placebo group) withdrew from the study because of adverse effects. Hematologic test results were not significantly affected by the administration of quetiapine. Low-dose quetiapine was not shown to be more effective than placebo, leading the researchers to conclude that a daily dosage of more than 250 mg of quetiapine is optimum. Treatment with quetiapine was associated with clinically significant weight gain (an increase of more than 7 percent from baseline weight) in 25 percent of the patients in the high-dose group, compared with 16 percent of patients in the low-dose group and 5 percent in the placebo group.

The authors conclude that quetiapine, in dosages of more than 250 mg, was effective for the treatment of acute exacerbation of chronic or subchronic schizophrenia and may represent an advance in the treatment of patients with schizophrenia, especially treatment-resistant patients. Further studies of this drug, both in fixed doses and in comparison with other well-known antipsychotic medications, are warranted.

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Copyright © 1998 by the American Academy of Family Physicians.

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