Progress in the Treatment of Bipolar Depression: Advances and Challenges

Some of the most challenging facets of bipolar disorder involve the management of its depressive symptoms. This article will focus on the pharmacologic management of this phase of bipolar disorder, describing the evidence base for controlled studies, emerging treatments, and expert recommendations. An unmet need exists for acute and maintenance treatments that target depressive symptoms in bipolar disorder. Depression predominates over the course of both bipolar I (BP I) and bipolar II (BP II) disorders, occurring more than 3 times as frequently as manic and hypomanic symptoms combined in BP I,1 and nearly 40 times as frequently as hypomania in BP II.2 Patients repeatedly attribute greater impairment in their work, family life, and psychosocial functioning to depressive symptoms than to mania.3 Even more problematic, the majority of attempted suicides occur in states of depression, in which the rate is 20 times higher than in the general population.4 A significant challenge facing clinicians is the misdiagnosis or underdiagnosis of bipolar depression. Perhaps this is because it presents itself less dramatically and is more difficult to recognize. A large French multicentered study of patients experiencing a major depressive episode, as classified by DSM-IV, found that when systematic methods for identifying hypomania were employed, the rate of BP II disorder nearly doubled, increasing from 22% to 40% of such patients.5 Similarly, when the Mood Disorder Questionnaire was used in a primary care clinic, more than one fifth of patients receiving antidepressants for the treatment of depression screened positive for bipolar disorder.6 Before this assessment, bipolar disorder had not been diagnosed in the majority of these patients. It is clear that early discrimination between bipolar disorder and other psychiatric illnesses, particularly major depressive disorder, is essential to minimize misdiagnosis and provide safe and effective care.