While studies in the past have focused more on treatment of the manic phase of bipolar disorder (BD), recent findings demonstrate the depressive phase to be at least as debilitating. However, in contrast to unipolar depression, depression in bipolar patients exhibits a varying response to antidepressants, raising questions regarding their efficacy and tolerability. Methods. We conducted a MEDLINE and Cochrane Collaboration Library search for papers published between 2005 and 2011 on the subject of antidepressant treatment of bipolar depression. Sixty-eight articles were included in the present review. Results. While a few studies did advocate the use of antidepressants, most well-controlled studies failed to show a robust effect of antidepressants in bipolar depression, regardless of antidepressant class or bipolar subtype. There was no significant increase in the rate of manic/hypomanic switch, especially with concurrent use of mood stabilizers. Prescribing guidelines published in recent years rely more on atypical antipsychotics, especially quetiapine, as a first-line therapy. Conclusions. Antidepressants probably have no substantial role in acute bipolar depression. However, in light of conflicting results between studies, more well-designed trials are warranted. 1. Introduction Bipolar disorder (BD) is a devastating illness, carrying an immense burden of both morbidity [1] and all-cause mortality [2], including high rates of completed suicide [3]. With a lifetime prevalence of 1.5–2% in Europe [4] and a similar prevalence in the USA [5], much attention has been drawn to assessing potential treatments for alleviating the symptoms of this condition, manic and depressive alike. However, while clinical focus in the past tended to be more on the manic phase of the disorder, recent findings illustrate the need to focus on effective treatment strategies for the depressive phase, for several reasons. First, observations of the natural course of BD show the considerable amount of time spent in the depressive phase compared to the manic phase (30% on average compared to 10% in bipolar 1 disorder) [6], leading to severe morbidity, including a marked occupational impairment [7]. Second, the depressive phase of BD is more prone to suicide [8]. Incomplete remission, with enduring subsyndromal depressive symptoms, has been demonstrated both to cause functional impairment [9] and increase the risk of relapse [10], emphasizing the importance of optimizing the treatment for the depressive phase of BD. Since their conception, antidepressants have been the mainstay of
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