Mania Risk Seen in Treating Bipolar Patients With Antidepressants Alone

Antidepressant monotherapy in patients with bipolar disorder appears to be associated with an increased risk of mania, according to a report published online June 17 in AJP in Advance.

In contrast, no increased risk of mania was seen in patients receiving an antidepressant while treated with a mood stabilizer as well, highlighting the importance of avoiding use of an antidepressant alone in the treatment of bipolar disorder, said the researchers, who are affiliated with Sweden’s Karolinska Institute and University of Gothenburg and the University of Pennsylvania.

They used Swedish national registries to identify 3,240 patients with bipolar disorder who started treatment with an antidepressant and had no antidepressant treatment during the previous year. Patients were categorized as those receiving antidepressant monotherapy and those receiving an antidepressant plus a mood stabilizer. The researchers compared the rate of mania at less than three months and at three to nine months after the start of antidepressant treatment with the rate reported during a preceding nontreatment period.

Nearly 35 percent of the patients were treated with an antidepressant alone. The increased risk of treatment-emergent mania—which had a hazard ratio of 2.83—was confined to patients on antidepressant monotherapy. Among patients treated with a concurrent mood stabilizer, no acute change in mania risk was seen during the three months after the start of antidepressant treatment, and a decreased risk was found during the period three to nine months after treatment initiation.

“Whether antidepressants should be prescribed to treat depression in bipolar disorder has been debated for decades,” the researchers noted. “At the core of this debate is weighing the clinical benefit of antidepressant treatment against risk of worsening the illness by inducing mania or instability. Our study suggests that use of an antidepressant in conjunction with a mood stabilizer does not increase the risk of mania. This is important because treatment options for bipolar depression are urgently needed; patients with bipolar disorder spend most of their time in depressive episodes, and depressive symptoms are the leading cause of impairment and morbidity in bipolar patients.”

Michael Thase, M.D., a professor of psychiatry at the University of Pennsylvania and one of the study co-authors, said that even though current practice guidelines recommend using antidepressants in combination with mood stabilizers in bipolar disorder patients, in Europe the practice of monotherapy is not uncommon. “Our findings suggest that antidepressants alone are associated with increased manic switching, and when it happens, it happens pretty quickly,” he told Psychiatric News. “The converse finding is that patients who got mood stabilizers while treated with antidepressants not only did better in the short term, but had an improved course in the long run. This means if you can prevent cycling or switching to any degree, your patients have a better chance of staying well over the long-term.” ■

“The Risk of Switch to Mania in Patients With Bipolar Disorder During Treatment With an Antidepressant Alone and in Combination With a Mood Stabilizer” can be accessed here.