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Research Update on Treatment of Depression in Bipolar Disorder

Depression in bipolar disorder is an important component of bipolar disorder. Yet most bipolar research prior to a few years ago focused more on the overall treatment of the disorder rather than treatments to help the depression itself. Depression in bipolar disorder can often last longer than manic episodes, and it often causes greater suffering and potential for harm. People with bipolar disorder in the midst of a depressive episode are at greater risk for suicide than people who only suffer from depression. Depression in bipolar disorder is often referred to as simply “bipolar depression.”

Depression in the context of bipolar disorder can often be misdiagnosed or treated incorrectly. A few studies published in the past year help shed some light on the effectiveness of various treatments for bipolar depression.

In early 2007, a study was published in the New England Journal of Medicine that examined the progress of 366 patients with bipolar disorder and depression. The study, called the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), treated patients for six months with lithium and other mood stabilizers. When one of two antidepressants (bupropion (Wellbutrin) or paroxetine (Paxil)) were added, the researchers discovered the antidepressants had no more effect on depression than adding a placebo or sugar pill. Patients taking these drugs were also no more likely to develop mania, though, contrary to popular professional belief.

This study was considered more realistic, real-world research than previous studies, because patients were more representative of real-world patients undergoing normal, real-world treatments. Patients in the study had different types of bipolar disorder, and some had additional diagnoses, such as anxiety or addictive disorders. The patients could continue any treatment they were already receiving and they were allowed to reject any antidepressant they did not want to take. In many studies, the outcome is judged by changes on a symptom rating scale; in this trial, recovery was defined as the absence of mood symptoms for two months. The unusual study design may help to explain why the results contradict earlier research suggesting that antidepressants can be effective in bipolar depression.

Research on intensive psychotherapy for the treatment of bipolar depression found it was a positive treatment for most. A little less than three-hundred patients were divided into four groups. Three of the groups were given different kinds of intensive psychotherapy, up to 30 sessions in nine months. The fourth group received three sessions in six weeks of educational sessions about the illness and its treatment. All patients took mood stabilizers and some took antidepressant medication.

The intensive treatments studied included:

  • cognitive behavioral therapy — focused on problem-solving, scheduling, stress management, and correction of self-defeating thoughts
  • interpersonal and social rhythm therapy — focused on problems in personal relationships and disrupted social and biological routines
  • family-focused therapy — focused on relatives to improve their communication with the patient, avoid creating stress that provokes symptoms, and develop plans to prevent relapse

Psychotherapy patients also received information about the disorder and the need to take medications, relapse prevention planning, and lessons in illness management. The study appeared in the April 2007 issue of the Archives of General Psychiatry.

The three intensive treatments were equally effective, and all three were more effective than educational information sessions alone. Patients receiving intensive therapy recovered, on average, a month sooner, and they were about 60% more likely to be well in any given month of the study.

Common drug treatments for acute bipolar depression are lithium and the anticonvulsant lamotrigine (Lamictal). To prevent depression from returning after recovery, clinicians may continue to prescribe these drugs and add others, including the antipsychotic drugs olanzapine (Zyprexa) and quetiapine (Seroquel). Fluoxetine (Prozac) and other antidepressants provide another option. Although the FDA has approved a combination of olanzapine and fluoxetine for bipolar depression, the effectiveness and safety of antidepressants in bipolar disorder are still disputed.

Effective treatment of bipolar depression appears to include intensive psychotherapy along with management on appropriate medications. Although specific antidepressant medications were not found helpful in the above study, many doctors and psychiatrists feel it is in the best interests of most patients to consider an antidepressant medication while in the midst of a depressive episode in bipolar disorder.


Belmaker RH. “Treatment of Bipolar Depression,” New England Journal of Medicine (April 26, 2007): Vol. 356, No. 17, pp. 1771–73.

Benazzi F. “Bipolar Disorder — Focus on Bipolar II Disorder and Mixed Depression,” Lancet (March 17, 2007): Vol. 369, pp. 935–45.

Miklowitz DJ, et al. “Psychosocial Treatments for Bipolar Depression: A 1-Year Randomized Trial from the Systematic Treatment Enhancement Program,” Archives of General Psychiatry (April 2007): Vol. 64, pp. 419–27.

Sachs GS, et al. “Effectiveness of an Adjunctive Antidepressant Treatment for Bipolar Depression,” New England Journal of Medicine (April 26, 2007): Vol. 356, No. 17, pp. 1711–22.

Research Update on Treatment of Depression in Bipolar Disorder

Marina Benjamen, Ph.D.

Marina Benjamen, Ph.D. is an award-winning journalist and writer, with wide-ranging interests across the arts and sciences. After serving as Arts Editor of the New Statesman, Deputy Arts Editor at the Evening Standard, she wrote op-ed columns for the Daily Express and Scotland on Sunday. In 2012, she joined the team that launched the online magazine Aeon, where she now works as a senior editor.

APA Reference
Benjamen, M. (2020). Research Update on Treatment of Depression in Bipolar Disorder. Psych Central. Retrieved on August 12, 2020, from
Scientifically Reviewed
Last updated: 30 Jul 2020 (Originally: 17 May 2016)
Last reviewed: By a member of our scientific advisory board on 30 Jul 2020
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