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Antidepressants in the Treatment of Bipolar Disorder: Decoding Contradictory Evidence and Opinion

For many people with bipolar disorder, the goal of consistent mood stabilization is never achieved. Rates of relapse and inter-episode subsyndromal symptoms are high.1−3 On average, patients in these studies were well only for about 50% of the time or less. Furthermore, bipolar disorder has not only an extreme level of morbidity, but also a very significant mortality rate due to suicide—estimated to be approximately 15%.4−6 The role of antidepressants in the treatment of bipolar disorder poses critical, but controversial, questions. While it is generally accepted that mood stabilizers form the foundation for treating bipolar disorder, the effectiveness and safety of adjunctive antidepressant medications have not been definitively established. Research on this problem is extremely difficult to undertake, given the unstable nature of the illness and the requirement for multiple interventions over long periods of time. Reviews and meta-analyses from highly regarded academic centers have yielded contradictory findings and given rise to conflicting opinions. Concern about the negative impact of antidepressant medications—that they caused rapid cycling and switches from depression into mania—was initially raised by Wehr and Goodwin.7 There continue to be questions about the propensities of antidepressants to cause cycle acceleration, switches into hypomania or mania, and mixed states. The