At the recent International Society for Bipolar Disorders (ISBD) meeting, 2 experts debated the role of antidepressants in the treatment of bipolar disorder. Both sides of the debate presented rational interpretations of existing literature (thus the jest about more blood). Both speakers agreed there is very little evidence for the efficacy of antidepressants in the treatment of bipolar disorder, particularly for longer-term use. They disagreed regarding evidence for the capacity of antidepressants to exacerbate bipolar disorder. The risk of inducing manic symptoms was their main focus, although one should also consider risk of inducing mixed states and the risk of “mood destabilization,” ie, inducing cycling such that more mood-stabilizing medications are required than would be needed without the antidepressant. For all of these risks, there remains room for debate.
Yet such debate may be moot. Look closely at the benefit to risk ratio for treatment of manic episodes in bipolar depression. Imagine a competition, based on this ratio, between antidepressant modalities. In this competition, any treatment that can leap over the bar of efficacy can be compared on the basis of its potential to exacerbate bipolar disorder. If the efficacy bar is set close to zero, which both speakers agreed appears to be the case for antidepressants, then virtually any treatment with evidence of antidepressant effects in some form of depression can be considered for the treatment of bipolar depression. The competition comes down to evidence of exacerbation and other adverse effects and risks—not efficacy.
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This antidepressant debate, however rational, was moot before it began. Clinicians have at least 9 alternatives to antidepressants, all of which have as much evidence for efficacy in bipolar depression as antidepressants do. All 9 alternatives have less risk of inducing hypomania/mania, and at least 5 have very little risk at all—and most of them have additional benefits. The pharmacotherapies have significant risks and warrant careful discussion with patients and individualized decision making. But for the benefit to risk ratio for mania, there is no need for further debate—or blood.