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The use of antidepressants for acute treatment of bipolar depression is a controversial topic in the world of psychiatry today. Studies assessing the propensity of antidepressants to produce a “switch” into mania or hypomania, as well as those evaluating the efficacy of antidepressants in treating bipolar depression, have displayed mixed results. Despite conflicting data, about 50% of patients with bipolar depression are prescribed an antidepressant.1,2 A systematic review and meta-analysis of 12 randomized controlled trials published in 2004 found antidepressants to be both safe and effective for the treatment of bipolar depression.3 More recent randomized, controlled trials of antidepressants have demonstrated different results. Consequently, a systematic review and meta-analysis reassessing the efficacy and safety of antidepressants for acute bipolar depression was recently published in the Journal of Clinical Psychiatry in October of 2010.4

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Fifteen randomized, double-blind trials comparing acute (4-16 weeks) antidepressant treatment with either an active (antidepressant or other pharmacologic medication) or placebo control in adult patients with bipolar I or II depression were included in this meta-analysis. The primary outcome measures were clinical response and remission, as measured by symptom reduction on diagnostic scales. Safety was also assessed by evaluating “switch” into mania or hypomania, also based on diagnostic scale assessments. Most trials were conducted in outpatients and were 6 to 8 weeks in duration. Patients ranged from 18-71 years of age and about 61% were female.

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Randomized, placebo-controlled trials evaluating the efficacy of antidepressants (paroxetine, fluoxetine, imipramine, bupropion) for the treatment of bipolar depression displayed no statistically significant differences in clinical response, remission, or switch rates. Randomized, active-controlled (lithium, lamotrigine, divalproex, idazoxan, L-sulpiride) trials assessing antidepressant (citalopram, paroxetine, bupropion, amitriptyline, fluoxetine) efficacy also yielded no statistically significant difference in the primary outcome measures. Additionally, head-to-head antidepressant trials revealed no statistically significant differences in clinical response and remission.

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Authors of this meta-analysis concluded that antidepressants for the acute treatment of bipolar depression are not associated with improved efficacy or an increased risk of “switch” into mania. It should be noted that different depression rating scales, along with different criteria to define response, remission, and switch, were used across trials. In the placebo-controlled trials and those comparing antidepressants to other pharmacologic medications, about 70% of patients received co-treatment with a mood stabilizer. The meta-analysis combined results from studies evaluating antidepressant monotherapy with those in which patients received co-treatment with a mood stabilizer. Though results from studies evaluating antidepressant monotherapy are valuable, treatment guidelines recommend the use of antidepressants in combination with a mood stabilizer. Thus, it seems inappropriate to include antidepressant monotherapy studies in this meta-analysis since this is not consistent with current clinical practice. 

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Though antidepressants do not appear to effectively treat acute bipolar depression, studies of longer duration in patients with more severe or chronic depressive symptoms should be conducted. Since most of these studies averaged 6 to 8 weeks in duration, the full benefit of antidepressant therapy may not have been revealed. Additionally, the majority of studies included in this meta-analysis ...

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