Extending Hope: Prolonged Antidepressant Treatment in Bipolar Disorder


Published September 2023

By Lauren DeSouza- Master of Public Health, Simon Fraser Public Research University – Canada


Staff Research and Content Writer

© Copyright – SUD RECOVERY CENTERS – A Division of Genesis Behavioral Services, Inc., Milwaukee, Wisconsin – September 2023 – All rights reserved.

A new study could revolutionize the way we treat bipolar disorder.

 In a world-first clinical trial, researchers from Canada found that extending the duration of antidepressant treatment from 8 weeks to 52 weeks could help prevent or delay depressive relapses for patients with bipolar disorder. These results challenge current clinical guidelines and could change the way we treat patients with bipolar disorder.

What is bipolar disorder? 

Bipolar disorder is a mental illness that causes extreme mood swings. Patients cycle through periods of intense emotional highs (mania or hypomania) and lows (depression).

When we think of bipolar disorder, the first thing that comes to mind is often the “manic” side, wherein a person experiences a very “up” mood and energetic, frantic behavior. However, people with bipolar disorder experience depressive episodes three times more often than they experience manic episodes. And these depressive episodes are just as harmful to their health and well-being. People with bipolar disorder experience suicidal attempts and deaths by suicide at a rate 18 times higher during their depressive episodes than during their manic episodes. Safe and effective treatment for the depressive side of bipolar disorder is quite literally life-saving.

What is the current treatment for depression in patients with bipolar disorder?

Providers often prescribe antidepressants to treat acute depression in patients with bipolar disorder. The use of antidepressants in combination with the mood stabilizers or antipsychotic medications used to treat their bipolar disorder is referred to as antidepressant adjunctive therapy.

 While antidepressant adjunctive therapy is commonplace and prescribed to nearly 60% of patients, little is known about its safety and efficacy. In particular, researchers and clinicians have expressed concerns that antidepressants may induce mania, mixed states, or rapid cycling between mania and depression among patients with bipolar disorder.

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Clinical practice guidelines recommend that patients discontinue using this antidepressant once they have been in remission from their depression for at least eight weeks.  However, little is known about how well this treatment works for preventing depressive relapses.

What did this study do?

Researchers at the University of British Columbia conducted a randomized clinical trial comparing the standard treatment for depression in patients with bipolar disorder to a an extended duration treatment. The study aimed to understand better the efficacy and safety of treating patients with antidepressants longer than current guidelines recommend.

 Patients in this study were recruited from outpatient clinics. They were eligible if they had bipolar disorder, were being treated for depression with either adjunctive escitalopram or adjunctive bupropion XL, and had been in remission from their depression for at least two weeks.

 Patients were divided into two treatment groups. The control group received the standard treatment of an adjunct antidepressant, which was discontinued eight weeks post-remission as per clinical guidelines. The treatment group continued to take the antidepressant for 52 weeks after going into remission. The researchers wanted to see how many patients in each group experienced a depressive relapse and the average time it took for the relapse to occur.

What were the results?

The results of this study were mixed. Upon initial analysis, it did not appear that the longer duration of treatment was beneficial in preventing depressive relapse. The relapse rates between the control group (46%) and the treatment group (31%) were not statistically significant, meaning there was no clear benefit to a longer duration of treatment.

 However, the researchers conducted another analysis excluding relapse events in the first six weeks of treatment. Patients in both groups received the same treatment during these first six weeks. By excluding these first six weeks, the researchers could more accurately compare the differences in the two treatment durations.

 Based on this analysis, patients who continued antidepressant treatment for 52 weeks were 40 percent less likely to experience a relapse of any mood event compared to those treated for eight weeks. They were also 59 percent less likely to experience a depressive episode during the study. Specifically, 31 percent of patients in the control (8-week) group had a depressive episode within the 52-week study period compared to only 17 percent of the treatment (52-week) group.

 Dr. Yatham, lead author of the study, summarizes this finding in a news piece for the UBC Faculty of Medicine News:

 From the point where the two groups began receiving different treatments, we see a significant benefit for patients who continued treatment with antidepressants,”

 There was no significant difference in the rate of manic episodes or the rate of adverse events between groups. The study found that both durations of adjunct antidepressant treatment were equally safe, and few people discontinued treatment from either group due to adverse side effects. This finding eased the concern that extended antidepressant treatment could induce mania or rapid mood cycling.

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What are the implications of these findings?

This study found that adjunct antidepressant treatment for patients with bipolar disorder is safe and does not lead to serious adverse effects or a worsening of patients’ bipolar disorder.

 It is unclear whether or not there is a benefit to using antidepressants for longer than recommended by clinical guidelines. While the analysis did suggest that a longer duration could prevent or prolong the time until a depressive relapse, it was not strong enough to draw a firm conclusion. The study instead concludes with support for the current clinical guidelines for bipolar disorder.

 Ultimately, this study opens the door to future research into adjunct antidepressant treatment and potential new treatment options for patients with bipolar disorder.


Lakshmi N. Yatham, Shyam Sundar Arumugham, Muralidharan Kesavan, et al. “Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression.” New England Journal of Medicine, 2023; 389 (5): 430 DOI: 10.1056/NEJMoa2300184

 Modern antidepressants may reduce risk of relapse for patients with bipolar depression. UBC Faculty of Medicine. Published August 3, 2023. Accessed from: https://www.med.ubc.ca/news/modern-antidepressants-may-reduce-risk-of-relapse-for-patients-with-bipolar-depression/