Adjunctive antidepressants little better than placebo in stemming mood relapse in bipolar 1

Key takeaways:

• Adjunctive antidepressants led to no significant delay in mood episodes after remission of bipolar depression.
• Researchers said the results may not apply to treatment with other antidepressants.

Continuing adjunctive antidepressant therapy for 52 weeks after depressive episode remission in patients with bipolar 1 disorder did not significantly delay further mood episodes vs. stopping treatment after 8 weeks, according to a study.

The time to onset of depression, mania and other mood episode indications did not differ significantly between those given placebo after 8 weeks and those given escitalopram or bupropion XL for 52 weeks, researchers reported in The New England Journal of Medicine.

The multisite, double-blind, randomized, placebo-controlled trial enrolled 177 participants recently in remission from a depressive episode and taking either escitalopram or bupropion XL as adjunctive treatment to a mood stabilizer, second-generation antipsychotic agent or both.

Ninety participants continued adjunctive treatment for 52 weeks, and 87 tapered adjunctive treatment after 6 weeks, replacing it with placebo at 8 weeks. For all participants, treatment with mood stabilizers and antipsychotic agents continued.

Study participants were assessed every 2 to 4 weeks for manifestation of a mood event, such as depression, mania or a suicide attempt.

In the 52-week group, 31% of patients (n = 28) experienced a mood event vs. 46% of patients in the 8-week group (n = 40), researchers reported.

The 52-week group’s hazard ratio for time to any mood episode relative to the 8-week group was 0.68 (95% CI, 0.43-1.1). A sensitivity analysis of mood events past 6 weeks, after the placebo group began tapering off treatment, showed a time-to-episode hazard ratio of 0.6 (95% CI, 0.37-0.98).

The hazard ratio for a manic or hypomanic event in the 52-week group was 2.28 (95% CI, 0.86-6.08), while the hazard ratio for a depressive event was 0.43 (95% CI, 0.25-0.75). However, confidence interval widths on those outcomes “were not adjusted for multiple comparisons, so no definite conclusions should be drawn from these results,” the researchers wrote.

Both groups had similar incidence of adverse events, with no serious adverse events observed in either group.

The study’s main limitation was slow recruiting amid the COVID-19 pandemic, and funding expired before the planned sample size was reached. Its findings also have limited generalizability because most trial participants were recruited from sites in India, with 87% being Asian, the researchers wrote.

The trial population was also skewed toward patients who responded to escitalopram and bupropion XL, and results may not be applicable to treatment with other antidepressants.

The researchers wrote that despite these limitations, the findings shed some light on the understudied effects of antidepressants as maintenance treatment after remission of acute depression in patients with bipolar 1 disorder.