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Antidepressant Action of Atypical Antipsychotics: Focus on Ziprasidone Monotherapy, With a Few Twists in the Tale

J Clin Psychiatry 2013;74(3):e193-e196
10.4088/JCP.13f08410

Ziprasidone has many pharmacodynamic properties that suggest it may have antidepressant action. Ziprasidone has established antimanic efficacy, and therefore, there is reason to hope that ziprasidone may be useful in the treatment of depression, especially when there is a risk of a switch into mania. A recent randomized controlled trial (RCT), however, found that ziprasidone monotherapy was no better than placebo in patients with major depressive disorder. Earlier RCTs had found ziprasidone to be ineffective in bipolar depression. These findings do not encourage the use of ziprasidone monotherapy to treat depression. Assuming that these findings are valid, a second take-home message is that clinicians should not rely too much on pharmacodynamic properties to guide expectations of clinical efficacy. Last, but not least, a note is presented on how evidence-based medicine principles should be applied in the interpretation of the results of the ziprasidone RCT in major depressive disorder with regard to a clinical case in point.