Lithium overcomes the influence of 5-HTTLPR gene polymorphism on antidepressant response to sleep deprivation.
To the Editors: Several recent studies have shown that mixed or depressive episodes in patients with bipolar I disorder can be successfully treated with atypical antipsychotic monotherapy. Randomized, double-blind, placebo-controlled trials have shown efficacy for quetiapine in bipolar depression and for aripiprazole, risperidone, and ziprasidone in bipolar mixed episodes. However, a major concern is that, in some patients, certain atypical antipsychotic agents have been associated with metabolic adverse events, such as weight gain, insulin resistance, and dyslipidemia. Guidelines from the Consensus Development Conference on Atypical Antipsychotic Drugs and Obesity and Diabetes recommend monitoring such patients closely or selecting a lower-risk agent. Among these agents, ziprasidone is known to have little or no adverse effect on body weight or metabolic parameters. Furthermore, the receptor profile of ziprasidone is predictive of antidepressant activity (it is a potent agonist at 5HT1A receptors and a modest inhibitor of serotonin and norepinephrine reuptake in vitro), although a controlled clinical trial of the drug in the treatment of bipolar depression has not yet been published. In our clinic, we have successfully used ziprasidone monotherapy to treat adult patients with bipolar I disorder who presented with mixed or depressive episodes. These patients were treatment refractory and, as such, received high doses of ziprasidone. None were considered at risk for cardiac arrhythmias, so electrocardiographic monitoring was not used. Moreover, the use of highdose ziprasidone without corrected QT interval abnormalities has been documented. The patients had also gained substantial amounts of weight on their prior (ineffective) therapies. We have observed marked clinical improvement, and substantial weight loss, with the ziprasidone treatment, presumably a reversal of medication-associated weight gain from the prior agents. We review the case reports of 4 of these patients here. In each case, ziprasidone was initially added to the patients’ existing regimen, and then the dose was titrated upward as clinically indicated. Ziprasidone was dosed twice daily with food. The goal was to taper or discontinue some or all of the ineffective medications, consistent with achieving and maintaining the best clinical outcome. Outcome measures were the Beck Depression Inventory, Second Edition (BDI-II), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression–Severity (CGI-S) scale. All 4 patients achieved full remission, defined as a normalization of scores on the YMRS and the BDI-II. The meanCGI-S score dropped from 5.8 at the index visit to 1.3 at the last recorded visit (mean follow-up period, 5.8 months). Weight loss ranged from 16 to 66 lb.