Extrapyramidal Adverse Events Associated With Atypical Antipsychotic Treatment of Bipolar Disorder

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Second-generation antipsychotics (SGAs) have generally replaced classic neuroleptics in managing bipolar disorder because of their property of inducing extrapyramidal symptoms (EPS) less frequently than conventional agents. However, EPS and tardive dyskinesia both remain a concern especially in bipolar patients who may be at greater risk of developing these unwanted events. Hence, the aim of this study was to identify a definite rank order of EPS potential among such agents. All original research articles published in English on the use of SGAs for the treatment of bipolar patients were identified through a comprehensive Medline search. Only double-blind, randomized, placebo- and/or active comparator-controlled studies evaluating the effectiveness of atypical antipsychotics in bipolar patients were included in this article. Available literature data seem to suggest that EPS may occur in a significantly greater proportion of aripiprazole-treated patients than placebo-treated patients. The relevant bias characterizing most of quetiapine trials makes the finding that the incidence of EPS does not differ statistically between medicated and placebo groups doubtful. Among SGAs, risperidone seems to be associated with the highest risk of inducing EPS at doses lower than 6 mg/d. Conversely, data on olanzapine appear to be quite reassuring. Although it has been reported that there are no statistically significant differences between ziprasidone- and placebo-treated patients in the incidence rates of EPS, this information requires further confirmation. Thus, as it regards the risk of inducing EPS, among SGAs, olanzapine should be considered a first-choice medication for bipolar patients. However, clinicians should take into consideration the relatively high risk of metabolic complications associated with olanzapine use as well as with most of the other SGAs.

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