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`Switching' Risks Minimal In Bipolar Treatment

Antidepressants can be both safe and effective in the treatment of bipolar depression, without risk of "switching" patients to mania.

Antidepressants are effective in the treatment of bipolar depression and are safe when used for short-term treatment. That is the conclusion of new research whose findings do not support a risk of "switching" patients to mania.

A wide-ranging review of data from randomized controlled trials of antidepressants in bipolar patients also found that selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) are more prudent choices for first-line therapy than tricyclics.

The data were reported in the September American Journal of Psychiatry. The analysis, which was not supported by any pharmaceutical industry funding, was done with the help of the Cochrane Collaboration Depression, Anxiety, and Neurosis Group in the United Kingdom.

"The gap between practice and theory should make us all uncomfortable," wrote the authors, led by Guy Goodwin, M.D., Ph.D., a professor of psychiatry at Warneford Hospital in Oxford, U.K. The question at hand, they noted, is how best to treat a patient in a depressive phase of bipolar disorder. In most countries, the authors stressed, "patients are offered antidepressants with little deliberation. By contrast, in all treatment guidelines, experts appear to agonize over whether antidepressants should be offered at all, at least as monotherapy."

Goodwin and his coauthors systematically assessed data from randomized controlled trials of antidepressants in the short-term treatment of bipolar depression. Using rigorous methods developed by the Cochrane Collaboration, they sought to "produce the best available quantitative estimates of the risks and benefits of antidepressant treatment in bipolar disorder."

The group reviewed 12 randomized, controlled trials, with a total of 1,088 patients enrolled. Five of these trials were direct comparisons of a medication and placebo; three-quarters of those patients were on a concurrent mood stabilizer or an atypical antipsychotic.

The authors noted that one limitation of the study was the fact that "the numbers of bipolar depressed patients entered into clinical trials is around 1 percent of the figures for unipolar depression." However, "the data nevertheless strongly support an average positive efficacy for antidepressants versus placebo in trials up to 10 weeks."

They added, "There is no coherent basis for doubting that conventional antidepressants have efficacy in bipolar depression on the basis of the existing evidence."

Because the trials reviewed were relatively short (between 4 and 12 weeks), the rates of switching from depression to mania were low, and overall antidepressants "did not induce more switching to mania." Switching in patients on antidepressants in the trials occurred at a rate of 3.8 percent, compared with 4.7 percent for those taking a placebo.

Six other trials compared two antidepressants. In these trials, the rate of switching was noted to be 10 percent for tricyclics, compared with only 3.2 percent for all other antidepressants combined.

Goodwin and his colleagues compared their conclusions with the APA Practice Guideline for the Treatment of Patients With Bipolar Disorder, and determined that contrary to what the practice guideline notes—recommending lithium or lamotrigine as first-line treatment for bipolar depression—"there is no strong reason to avoid antidepressants" for these patients. In fact, Goodwin and his colleagues concluded, "we advise adding an antidepressant as a first-line treatment" for those patients already taking a mood stabilizer.

Also in contrast to the practice guideline, which specifically recommends paroxetine and bupropion as antidepressants, Goodwin and colleagues saw "only very limited evidence for bupropion and only limited evidence for a special place for paroxetine among the SSRIs. To prefer either is to move beyond the evidence."

APA practice guidelines undergo regular revision, about every five years, according to Robert Kunkle, M.A., APA's senior program manager for practice guidelines. The bipolar guideline is scheduled for review in 2005. If evidence suggests that recommendations are dated, APA will develop and publish a guideline watch, a guideline revision, or both. Watches briefly summarize major developments since guideline publication that could lead clinicians to treat patients in a manner different from what the guideline recommends.

Finally, the authors concluded, future research is needed to answer several questions: Are patients with bipolar II disorder similar to patients with bipolar I in their response to antidepressants? Does use of antidepressants lead to mood instability or increased cycling? And "is there actually any disadvantage to the long-term use of non-tricyclic antidepressants for the prevention of depressive relapse?"

The report, "Antidepressants for Bipolar Depression: A Systematic Review of Randomized Controlled Trials," is posted online at <http://ajp.psychiatryonline.org/cgi/content/abstract/161/9/1537>.

Am J Psychiatry 2004 161 1537[Abstract/Free Full Text]

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