Antidepressant use in bipolar disorder linked to increased disease severity

Naveed Saleh, MD, MS, for MDLinx | April 06, 2018

Despite the uncertainties in treating bipolar disorder with antidepressants, patients did tend to increase the use of antidepressants when their illness was more severe, according to researchers in a recently published article in the Journal of Affective Disorders. The researchers also determined that bipolar II patients were treated with antidepressants more often than bipolar I patients.


In people with bipolar disorder, antidepressant use increases as their illness becomes more severe, new study finds.

“The heightened severity associated with antidepressants may reflect greater utilization of antidepressants during depressed mood states, and greater illness burden associated with depression rather than mood elevation,” wrote researchers led by Farnaz Hooshmand, MD, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA.

Antidepressants are the most common medications prescribed to treat bipolar disorder, yet little data on their use in the treatment of this condition exist. Moreover, data examining the efficacy and safety of such an intervention in bipolar disorder have varied widely.

Researchers suggest that antidepressants may help alleviate the symptoms of bipolar disorder for two possible reasons. First, antidepressant medications may treat the depressive component of bipolar disorder by means unmet by other drugs. Second, the three FDA-approved treatments for bipolar depression have antipsychotic components that limit tolerability among patients.

Even so, physicians know that antidepressant use in those with bipolar disorder may trigger mood instability and hypomania or mania.

In this study, researchers used data from 503 outpatients with bipolar disorder who were referred to the Stanford Bipolar Clinic between 2000 and 2011. Of these participants, 243 (48.3%) had bipolar I disorder and 260 (51.7%) had bipolar II disorder. The mean age of patients was 35.6 years and 58.3% were women. Participants had bipolar disorder for a mean duration of 17.7 years, and took an average of 2.3 core psychotropic medications.

Results of the study showed that, overall, 39.0% of participants used antidepressants. Rates of antidepressant use were higher among patients with bipolar II disorder (46.9%) than those of bipolar I disorder (30.5%, P=0.0002). Corresponding rates of antidepressant use in other studies have ranged between 30% and 80%.

Use of antidepressants among participants with bipolar II disorder was higher during periods of euthymia and subsyndromal symptoms but not during depression or mood elevation compared with those of participants with bipolar I disorder. “This finding,” wrote Dr. Hooshmand and coauthors, “could be related to increased use of antidepressants during depression in [bipolar disorder] I patients and decreased use of antidepressants during mood elevation in BD II patients.”

Participants with bipolar I disorder and bipolar II disorder who took antidepressants also took more core psychotropics and had higher rates of complex pharmacotherapy, defined as “≥4 mood stabilizers, antipsychotics, and/or antidepressants.” According to Dr. Hooshmand and coauthors, this finding, as well as other clinical variables examined during the study, is “consistent with overall higher severity of illness in BD patients taking versus not taking antidepressants.”

One limitation of this study is that its generalizability to a wider population may be limited. The participants were referred to a bipolar disorder specialty clinic in an affluent and well-educated suburban North California community.

Of note, researchers could not determine causality tying baseline antidepressant use and clinical correlates, such as whether antidepressant administration increased anhedonia or, conversely, whether anhedonia increased antidepressant administration. The researchers were also unable to determine the various reasons that the participants were prescribed antidepressants, such as anxiety or depression.

The authors concluded: “Given the commonly inadequate outcomes associated with bipolar depression and antidepressant use, further examination of this relationship is warranted in order to better understand mechanisms and clinical implications.”