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Am Fam Physician. 2004;70(2):379

The typical antipsychotic agents continue to be used in the acute mania phase of patients with bipolar disorder to provide rapid control of acute mania symptoms. Recently, questions have been raised concerning the safety of these agents in patients with bipolar disorder. Many researchers have suggested that the typical antipsychotic agents may worsen the course of bipolar disorder by switching patients into depression and increasing their risk of depressive episodes and rapid cycling. These agents also have safety issues, particularly those of acute extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome. The newer, atypical antipsychotic agents have a lower risk of side effects compared with the older, typical agents. However, there is limited literature available evaluating these two classes of medications in the treatment of patients with bipolar disorder. Tohen and associates evaluated the safety and efficacy of olanzapine (an atypical antipsychotic agent) and haloperidol (a typical antipsychotic agent) in patients diagnosed with acute mania.

The trial was a 12-week, multicenter, randomized, double-blind, parallel group study of patients who met the criteria for bipolar I disorder, manic or mixed type (with or without psychotic features) in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). Participants were included if they had a mania score of 20 or higher on a standardized scale, suggestive of an acute mania phase.

Patients were assessed at baseline and randomized to receive olanzapine (5, 10, 15, or 20 mg per day) or haloperidol (3, 5, 10, or 15 mg per day). Dosages were adjusted during the study period based on the clinical judgment of the attending physician.

Participants were assessed on a weekly basis with multiple standardized surveys, including one for quality of life. Patients who showed improvement in mania score at week 6 were allowed to complete the study; patients whose score did not improve were excluded from the final six-week continuation phase of the study. Adverse events were recorded at each visit, and vital signs, weight, and clinical laboratory tests were assessed at baseline, and at weeks 6 and 12, or when the patient discontinued randomized therapy.

There were 453 participants in the study. The rates of remission of mania symptoms were not significantly different in the olanzapine group than in the haloperidol group. There was a significant increase in the risk of rapid switching to depression and a significant worsening of extrapyramidal symptoms in those receiving haloperidol compared with those receiving olanzapine. Participants were more likely to have a weight gain with olanzapine. Participants who received olanzapine had a statistically significant greater improvement on quality-of-life measurement scores.

The authors conclude that olanzapine and haloperidol provide similar rates of remission in patients in the acute mania phase of bipolar disorder. They add that olanzapine does have a lower risk for extrapyramidal symptoms, but also has a higher risk of weight gain compared with haloperidol.

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