Antidepressants in Bipolar Depression: An Enduring Controversy

The proper place and the optimal use of antidepressants in treating bipolar depression continues to be an area of great interest and greater controversy with passionate opinions more common than good studies. Even the handful of meta-analyses in the area disagree with each other. Overall, the evidence that antidepressants are effective in treating bipolar depression is weak. Additionally, many experts and clinicians worry greatly about the capacity of antidepressants to cause affective switching or mood destabilization. Yet, in short term controlled studies, with most patients also taking mood stabilizers, antidepressants are not associated with switches into mania/hypomania. Evidence of cycle acceleration with antidepressants primarily reflects treatment with older antidepressants, e.g., tricyclics. Similar evidence with modern antidepressants such as selective serotonin reuptake inhibitors (SSRIs) is lacking. The key questions should not be: are antidepressants effective in bipolar depression?; And: do antidepressants worsen the course of bipolar disorder? Rather, the question should be focused on subgroups: for which patients are antidepressants helpful and safe, and for which patients will they be harmful? Predictors of affective switching with antidepressants include: bipolar I disorder (vs. bipolar II), mixed features during depression, tricyclics vs. modern antidepressants, rapid cycling and possibly a history of drug abuse, especially stimulant abuse. Additionally, a number of recent studies have demonstrated both the safety and efficacy of antidepressant monotherapy in treating bipolar II depression. Finally, a subgroup of bipolar individuals need antidepressants in addition to mood stabilizers as part of an optimal maintenance treatment regimen. (Reprinted with permission from Int J Bipolar Discord (2018) 6:25)