Antidepressants are commonly prescribed to treat acute depressive episodes in bipolar disorder, but their role as maintenance therapy has not been extensively studied. A recent paper published in the New England Journal sought to examine the efficacy of antidepressants as maintenance treatment after the remission of depression.

In this multisite, double-blind, randomized, placebo-controlled trial, maintenance of treatment with adjunctive escitalopram or bupropion XL was compared to discontinuation of antidepressant therapy. The cohort studied was patients with bipolar 1 disorder who had recently had remission of a depressive episode. Patients were randomly assigned to either continue treatment with antidepressants for 52 weeks after remission, or to switch to placebo at 8 weeks.

The primary outcome was any mood episode, which the authors defined by scores on scales measuring symptoms of hypomania or mania, depression, suicidality, and mood-episode severity; additional treatment or hospitalization for mood symptoms; or attempted or completed suicide. Secondary outcomes included time to an episode of mania or hypomania or depression.

The main finding of the study was that continuing antidepressants for 52 weeks did not significantly prolong time to mood relapse versus switching to placebo at 8 weeks (hazard ratio 0.68, 95% CI 0.43-1.10, P=0.12). With respect to the secondary outcomes, 11 patients in the 52-week group (12%) as compared with 5 patients in the 8-week group (6%) had mania or hypomania (hazard ratio, 2.28; 95% CI, 0.86 to 6.08), and 15 patients (17%) as compared with 35 patients (40%) had recurrence of depression (hazard ratio, 0.43; 95% CI, 0.25 to 0.75). There was no significant difference in the incidence of adverse events in the two groups.

A limitation of the study was that the planned sample size could not be reached due to the COVID-19 pandemic and expiration of funding. Also, a majority of patients recruited in this trial were from India, which may limit generalizability. Finally, since only bupropion XL and escitalopram were studied, these findings may not be applicable to other antidepressants.

Reference:
Yatham LN et al. N Engl J Med. 2023;389(5):430-440. Abstract.