No Need for Blood: Nine Alternatives to the Antidepressant Debate

No Need for Blood: Nine Alternatives to the Antidepressant Debate

Nine alternatives to antidepressants for bipolar depressionTable: Nine alternatives to antidepressants for bipolar depression

“More blood on the stage,” one attendee jokingly requested. 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.

Looked at this way, there are at least 9 alternatives to conventional antidepressants, which for ease of recall can be thought of as “3 columns of 3” as shown in the Table. Most of them have no evidence at all of exacerbating symptoms of bipolar disorder (cost, difficulty, hassle, potential adverse effects, yes; but not the potential for making the condition worse). In this respect, they easily exceed the benefit to risk ratio of conventional antidepressants.

Rare induction of manic symptoms has been reported for 4 of these treatment approaches. Although findings from a secondary analysis by Goldberg and colleagues1 indicate that lamotrigine is no more likely to induce hypomanic/manic symptoms than a placebo is, case reports suggest that at least a few patients can clearly get worse.2 There is only one old case report of omega-3 fatty acids inducing hypomania.3 For quetiapine, a case report and literature review conclude that induction of hypomania is possible but rare.4 Otherwise, there are no data—such as the data that were the focus of the ISBD debate—for this risk from the 9 options shown in the Table.

Therefore, the relative value of the 9 options in comparison with antidepressants for the treatment of bipolar depression should be evaluated on the basis of their other risks and adverse effects (and in some cases, additional benefits).

Not pills

Given the image of psychiatry as portrayed in the media, it is useful to have a list of treatment options that demonstrate that we are not simply “pill pushers.” Granted, the first item on the list—physical activity—is difficult to maintain routinely even for those of us who are not depressed. Given the profound anergy that often accompanies bipolar depression, advocating exercise as an antidepressant tool can have an opposite demoralizing effect if not presented carefully. Acknowledge that it will be extremely difficult, and keep the initial “dose” extremely low, almost laughably achievable. For example, Harvard’s Gary Sachs explains their program’s exercise recommendation: “put your shoes on, go to the door, and open it. Walk in any direction for 7.5 minutes, and then walk home.” One might explore the viability of just 3 to 5 minutes of some activity and build from there.


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