Adjunctive antidepressant maintenance ineffective in bipolar I depression

1. In this randomized controlled trial, adjunctive treatment with escitalopram or bupropion XL for 52 weeks was not superior to eight weeks in preventing relapse of mood episodes among patients with bipolar I depression.

2. The rates of adverse events were comparable across both approaches.

Evidence Rating Level: 2 (Good)

Study Rundown: Bipolar I disorder is characterized by episodes of mania and depressive symptoms. Depression often afflicts bipolar I patients more frequently than mania and is associated with a significantly elevated risk of suicidality. Second-generation antipsychotics are effective in treating acute depressive episodes and maintenance therapies for bipolar I are efficacious in preventing depression. Adjunctive antidepressants are utilized, often for extended periods, following an acute depressive episode to reduce the risk of relapse. However, evidence is limited in the efficacy of these adjuncts. The current study investigated the impact of a 52-week treatment period of adjunctive escitalopram or bupropion XL compared to an eight-week regimen among bipolar I patients who had had remission from a depressive episode. By 52 weeks, the two approaches yielded similar rates of recurrence of any mood episode, including mania, hypomania, and depression. The incidence of adverse events was also similar across the groups. The main limitations included a homogenous demographic makeup and lack of generalizability to antidepressants other than escitalopram or bupropion. These results showed that long-term adjunct with escitalopram or bupropion XL was not superior to short-term adjunct in the recurrence of mood episodes for patients with bipolar I following remission of a depressive episode.

Click here to read the study in NEJM

In-Depth [randomized controlled trial]: The current study was a multi-center, double-blind, randomized, placebo-controlled trial to investigate the impact of long-term maintenance adjunct therapy with escitalopram or bupropion XL in patients with bipolar I after a depressive episode. Patients 18 years of age or older were eligible for inclusion if they had a diagnosis of bipolar I disorder, had started receiving escitalopram or bupropion XL for an acute major depressive episode in the preceding 16 weeks, were receiving standard-of-care bipolar treatment with a mood stabilizer or a second-generation antipsychotic, and had been in remission from the depressive episode for at least 2 weeks. Exclusion criteria included current substance use disorder or current treatment with other psychotropic medications. Overall, 177 patients were randomized 1:1 to a 52-week treatment period of an antidepressant (either escitalopram or bupropion XL) or to a regimen where the antidepressant was switched to a placebo at eight weeks. The primary outcome was a composite of any mood episode, assessed by symptoms of hypomania or mania, depression, suicidality, hospitalization, or suicide attempt. By 52 weeks, 31% of patients in the 52-week group and 46% in the eight-week group had a primary outcome episode, yielding a hazard ratio of 0.68 (95% Confidence Interval [CI], 0.43 to 1.10; p=0.12). The hazard ratio of recurrence was 2.28 (95% CI, 0.86 to 6.08) for mania or hypomania (52-week versus eight-week) and 0.43 (95% CI, 0.25 to 0.75) for depression. The rates of adverse events were similar across the two groups. The study was stopped before full recruitment due to funding limitations. In summary, these results showed that for bipolar I patients who had had remission from an acute depressive episode, a 52-week treatment period of adjunct antidepressants did not offer benefits over a shorter eight-week period.

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