REVIEW OF: Altshuler L et al, Am J Psychiatry 2017;174(3):266–276. doi:10.1176/appi.ajp.2016.15040558

STUDY TYPE: Randomized, double-blind, multi-site comparison

Do antidepressants cause bipolar II patients to switch from depression to hypomania? It’s a controversial question, and you’ll find academic psychiatrists who will argue passionately that antidepressants are either safe or dangerous in these patients. The latest study appears to endorse the “safe” camp.

In this multi-site clinical trial, researchers conducted a 16-week study of 142 outpatients with bipolar II disorder. All were between 18 and 65 (mean age late 30s), and all met DSM-IV criteria for bipolar II disorder, major depressive episode. They were randomized to receive sertraline (N = 45; minimum target dose 100 mg/day), lithium (N = 49; minimum target dose 900 mg/day), or combination treatment with both (N = 48). The primary outcome was rate of switching to a hypomanic or manic episode, and secondary outcomes were treatment response, dropout rates, and side effects.

RESULTS
After 16 weeks, the switch rate (hypomania only) was 17.9% overall (19.4% lithium, 19.9% sertraline, and 13.4% combination treatment). There were no statistically significant differences in switch rate among the three treatment arms, although patients with a history of drug abuse (stimulants in particular) had a higher risk of switching. Most of the switches occurred in the first 5 weeks of treatment. The overall treatment response was 62.7%, also with no differences found between treatments. While rates of side effects did not differ, the dropout rate was higher in the lithium/sertraline arm (70.8%) than the monotherapy arms (55.1% for lithium, 42.2% for sertraline).

TCPR’S TAKE
This is the largest randomized double-blind trial comparing switch rates in bipolar II patients taking lithium, sertraline, or their combination. The findings suggest that in bipolar II disorder, monotherapy with an SSRI is as effective and as safe as combination therapy with lithium.

PRACTICE IMPLICATIONS
This is another data point endorsing the efficacy and safety of SSRI monotherapy in patients with bipolar II disorder. While it is the largest study to date, it is still relatively small, with only about 50 patients in each treatment arm. Some other studies have reported conflicting findings. Regardless of your medication decisions, watch particularly closely for a switch during the first 5 weeks of treatment.