Efficacy of Drugs in Bipolar Depression: What the Data Show

Note: For the first installment of this series, click here. For the third installment, click here.

This is the second installment of a new series in which clinically relevant research is briefly discussed and, perhaps more important, a few tips on how to read and interpret research studies are presented. Your feedback, suggestions, and questions are eagerly solicited at rajnish.mago@jefferson.edu

More efficacious treatments are sorely needed for the treatment of the major depressive episodes of bipolar I and bipolar II disorders (“bipolar depression”). For example, lamotrigine has been found to be more effective than placebo for delaying occur-rence of both depressive and, to a lesser extent, manic episodes during 18 months in patients with bipolar I disorder (who were recently or currently in a manic, mixed, or depressive episode and whose condition was first stabilized with the use of lamotrigine).¹ Its efficacy in the acute phase of bipolar depression is, however, much less clear.

The published literature on the treatment of acute bipolar depression with lamotrigine was somewhat misleading until recently. One clinical trial found lamotrigine to be more efficacious than placebo on at least some of the outcome measures.²

The American Psychiatric Association’s practice guideline for bipolar disorder advocates using lamotrigine as one of the first-line options for bipolar depression.³ However, 4 other randomized, placebo-controlled clinical trials (similar in size to the published one) were not published (although the results of 1 of these 4 were mentioned as part of a review article). These 4 trials did not find lamotrigine to be more efficacious than placebo on most of the outcome measures. This was a prominent example of publication bias in which studies that fail to find a treatment to be effective are much less likely to be published, thus significantly biasing the published literature in favor of the proposed treatment.⁴

TIP: In assessing whether a particular treatment is efficacious for a particular disorder, or reading a review or meta-analysis that attempts to do this, it is essential that all randomized, controlled clini-cal trials on the topic be taken into consideration. Unfortunately, this is commonly not done, so readers must be vigilant for this.

Finally, in 2008 the results of all 5 randomized, placebo-controlled studies of the efficacy of lamotrigine monotherapy for acute bipolar depression were published in a single article.⁵

These studies randomized about 200 patients each and lasted for 7 to 10 weeks. Three of the studies included only patients with bipolar I disorder, 1 included only those with bipolar II disorder, and 1 included patients with both. The final dosage of lamotrigine was 200 mg/d in 3 studies, 1 study compared 50 mg/d and 200 mg/d with placebo, and 1 study used a flexible dosage between 100 and 400 mg/d.

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