Ziprasidone Improves Mood With Possible Weight Loss Side Effects

September 28, 2011 · Posted in Current Treatments 

weight lossIn an open study of bipolar disorder treatment, Shefali Srivastava, Terence Ketter and colleagues at Stanford University evaluated ziprasidone as an aid to patients unresponsive to other medications. This study was part of the multi-center research program Systematic Treatment and Evaluation Program for Bipolar Disorder, or STEP-BD. During naturalistic treatment, ziprasidone was added to an average of 3.6 other psychotropic medications and 1.2 other nonpsychotropic medications patients had already been prescribed. The researchers found substantial improvement in mood with ziprasidone, particularly in the patients who had symptomatic levels of depression at baseline. The research team also observed a mean weight decrease from 195 + 50lbs at baseline to 183 + 47lbs at the final visit, with 34.3% of the patients achieving at least a 7% weight loss with ziprasidone.

Mean trial duration was 860 + 700 days, with no subsequent psychotropic agents added in 51.2% of the patients who had a mean trial duration of 221 + 272 days. Ziprasidone was discontinued in 57.3% of the 82 trials after a mean of 208 + 364 days. This was due to side effects in 26.8% of the participants and due to inefficacy for mood in 23.2%.

The investigators concluded that in bipolar patients treated naturalistically with complex pharmacotherapy, ziprasidone decreased overall bipolar illness severity, was helpful in patients with substantial depression at baseline, and also yielded clinically significant weight loss in about one-third of the patients.

Editor’s note: These data are notable because they support ziprasidone’s pattern of weight neutrality and because of the overall improvement in mood symptomatology the drug brought about.

Moreover, in this case ziprasidone was added to a mean of 4.8 other prescribed medications, re-affirming the need for complicated pharmacological regimens in most patients with this disorder. These data mirror what my colleagues and I found while providing naturalistic treatment to bipolar outpatients in the Stanley Bipolar Network. Complex regimens were typically required in order to achieve substantial long-term mood stabilization. (We published this research in the Journal of Clinical Psychiatry last year in the article, “Complexity of pharmacologic treatment required for sustained improvement in outpatients with bipolar disorder.”) The ziprasidone study also highlights the general need to study complicated treatment regimens in order to assess which combinations are most effective and how to develop the best treatment algorithms for achieving good long-term responses.

Most of the atypical antipsychotics have been studied in combination with a mood stabilizer, such as lithium or valproate, in formal randomized controlled clinical trials, and this combination has shown significant superiority over mood stabilizers alone. More complicated treatment regimens have not been systematically studied, despite the fact that many patients with bipolar illness require such regimens. Therefore, careful sequential augmentation trials to assess individual responsiveness and tolerability including detailed longitudinal self-ratings on the NIMH-LCM (or personal calendar, found here) are the most practical way to proceed to maximize chances of clinical remission.


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