A Review of the Role of Antipsychotics as an Augmentation Agent or Treatment Option for Patients with Treatment Resistant Unipolar Depression

Background: Patients with unipolar depression present a unique challenge for physicians who are considering therapeutic drug treatment. Physicians have historically treated patients who present symptoms of unipolar depression with SSRIs or other medications that are commonly prescribed to patients with non-unipolar depression. Many of these medications are ineffective for patients suffering from unipolar disorder. Recently, an exciting new treatment approach for the depressive symptoms related to unipolar disorder has emerged in the form of secondgeneration atypical antipsychotics. A wealth of empirical support for treating treatment-resistant bipolar depression is becoming increasingly available, but much less is understood regarding the efficacy of atypical psychotics in treating unipolar depression. Methods: An electronic literature review was conducted through PubMed, PsycINFO, the Cochrane Library, Web of Science, and Embase using the following search phrases: depression, unipolar depression, antipsychotics, second-generation antipsychotics, atypical antipsychotics, and depression treatment. There were no restrictions on publication year, type, or language. Meta-analyses and randomized clinical trials (RCTs) were considered. A sensitivity analysis was performed by excluding studies with small sample sizes and a high placebo effect. Discussion: Preliminary evidence for this treatment approach is promising, although additional clinical trials which more clearly elucidate the role of second-generation atypical antipsychotics in treating unipolar depressive symptoms may be warranted. Accordingly, this article discusses the second-generation atypical antipsychotics that have, to date, received empirical support for use in treating patients with unipolar disorder. Proposed mechanisms of action are discussed and current FDA approvals as well as approval status in different countries for usage are reviewed. Indications for future research are also proposed.