Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression

Lakshmi N. Yatham, Shyam Sundar Arumugham, Muralidharan Kesavan, Kanchana Ramachandran, Nithyananda S. Murthy, Gayatri Saraf, Yongdong Ouyang, David J. Bond, Ayal Schaffer, Arun Ravindran, Nisha Ravindran, Benicio N. Frey, Andrée Daigneault, Serge Beaulieu, Raymond W. Lam, Nithin Kondapuram, M. S. Reddy, R. P. Bhandary, Mysore V. Ashok, Kyooseob HaYong Min Ahn, Roumen Milev, Hubert Wong, Y. C.Janardhan Reddy

Research output: Contribution to journalArticlepeer-review


Background Antidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied. Methods We conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks. The primary outcome, assessed in a time-to-event analysis, was any mood episode, as 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. Key secondary outcomes included the time to an episode of mania or hypomania or depression. Results Of 209 patients with bipolar I disorder who participated in an open-label treatment phase, 150 who had remission of depression were enrolled in the double-blind phase in addition to 27 patients who were enrolled directly. A total of 90 patients were assigned to continue treatment with the prescribed antidepressant for 52 weeks (52-week group) and 87 were assigned to switch to placebo at 8 weeks (8-week group). The trial was stopped before full recruitment was reached owing to slow recruitment and funding limitations. At 52 weeks, 28 of the patients in the 52-week group (31%) and 40 in the 8-week group (46%) had a primary-outcome event. The hazard ratio for time to any mood episode in the 52-week group relative to the 8-week group was 0.68 (95% confidence interval [CI], 0.43 to 1.10; P=0.12 by log-rank test). A total of 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). The incidence of adverse events was similar in the two groups. Conclusions In a trial involving patients with bipolar I disorder and a recently remitted depressive episode, adjunctive treatment with escitalopram or bupropion XL that continued for 52 weeks did not show a significant benefit as compared with treatment for 8 weeks in preventing relapse of any mood episode. The trial was stopped early owing to slow recruitment and funding limitations. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00958633.)

Original languageEnglish
Pages (from-to)430-440
Number of pages11
JournalNew England Journal of Medicine
Issue number5
Publication statusPublished - 2023

All Science Journal Classification (ASJC) codes

  • Medicine(all)


Dive into the research topics of 'Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression'. Together they form a unique fingerprint.

Cite this