Bipolar II Depression: No Difference Between Monotherapy and Combined Therapy

Bipolar disorder: treatments
Bipolar disorder: treatments
Bipolar II depression therapy options revealed no significant differences in switch rate or treatment relapse.

The results of a randomized double-blind study published in the American Journal of Psychiatry reveal no significant differences in switch rates or treatment response associated with 3 different therapies for patients with bipolar II disorder.1

Compared with patients with bipolar I disorder, those with bipolar II often remain in the depressed phase for a longer duration than the hypomanic phase.2 Antidepressants are commonly prescribed as part of the treatment approach for such patients, despite concerns that they may increase the rate of cycling or switch to hypomania, whether used alone or combined with a mood stabilizer.3

Several studies have found that switch rates caused by antidepressants were lower in bipolar II vs bipolar I depression when the antidepressant was combined with a mood stabilizer.4,5 However, it is unclear whether “monotherapy with a selective serotonin reuptake inhibitor…will destabilize bipolar II patients with depression more than mood stabilizer monotherapy or combination therapy with a mood stabilizer,” wrote Lori L. Altshuler, MD, from the Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at the University of California, Los Angeles, and colleagues, who noted the need for additional treatment options for patients with bipolar II disorder.

In this 16-week trial, they compared switch rates, treatment response, and adverse effects associated with 3 different therapies: sertraline monotherapy, lithium monotherapy, or a combination of the 2 medications. The sample included 142 adult patients with bipolar II disorder and a current depressive episode who met a specific range of scores on various depression and mania scales. They were assessed weekly for the first 6 weeks, and biweekly for the remainder of the study period.

The findings show no significant difference between the 3 regimens, in terms of switch rates or treatment response. The overall treatment response was 62.7%, and 14% of patients experienced a switch to hypomania (12%) or severe hypomania (2%), typically within the first 5 weeks after treatment initiation. There were no incidents of a manic switch or hospitalization resulting from a switch. The highest dropout rate occurred with the lithium/sertraline combination, which is the regimen that is recommended most often in clinical practice.

Although further research is needed to support first-line therapy recommendations, these findings “support the possibility that, unlike in bipolar I patients, an antidepressant monotherapy may be appropriate and carry few risks in some patients with bipolar II disorder,” the authors concluded. It appears that “monotherapy in general, and sertraline monotherapy in particular, may be a viable option…which is of significant clinical import to patients and their physicians.”

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  1. Altshuler LL, Sugar CA, McElroy SL, et al. Switch rates during acute treatment for bipolar II depression with lithium, sertraline, or the two combined: a randomized double-blind comparison. Am J Psychiatry. 2017;174(3):266-276. doi: 10.1176/appi.ajp.2016.15040558
  2. Judd LL, Akiskal HS, Schettler PJ, et al. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003;60(3):261-269.
  3. Viktorin A, Lichtenstein P, Thase ME, et al. The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer  [published online October 1, 2014]. Am J Psychiatry. doi: 10.1176/appi.ajp.2014.13111501
  4. Joffe RT, MacQueen GM, Marriott M, et al. Induction of mania and cycle acceleration in bipolar disorder: effect of different classes of antidepressant. Acta Psychiatr Scand. 2002;105(6):427-430. doi: 10.1034/j.1600-0447.2002.02360.x
  5. Altshuler LL, Suppes T, Black DO, et al: Lower switch rate in depressed patients with bipolar II than bipolar I disorder treated adjunctively with second-generation antidepressants [published online February 1, 2006]. Am J Psychiatry. doi: 10.1176/appi.ajp.163.2.313