Review of: Bschor T, Kern H, Henssler J, Baethge C. Switching the antidepressant after nonresponse in adults with major depression: A systemic literature search and meta-analysis. J Clin Psychiatry 2016. doi:10.4088/JCP.16r10749. [Epub ahead of print]

Study type: Meta-analysis

Clinical trials have shown that the response rate of major depression to a course of antidepressants is 50% to 70%. After a non-response, what should we do? Increase the dose? Switch to another medication? Augment with a different one? Unfortunately, we have remarkably little to guide us in the way of empirical studies. The largest “real-world” study of antidepressants, the oft-cited STAR*D trial, enrolled plenty of patients and compared various strategies. Unfortunately, that study was not very informative, because there was no placebo group, and patients were not fully randomized to group assignments.

The authors of this meta-analysis sought evidence to answer a specific question: Is it better to stay the course with the original antidepressant, or is it better to switch? They searched the literature for studies that enrolled patients with major depressive disorder who did not respond to at least a 2-week trial of an antidepressant. These patients were then randomly assigned to either continuation of the same medication or a switch to a different one. They found eight relevant studies, and combining them, 783 patients were randomized to continuation arms while 844 were assigned to switching arms. Some of the studies blinded participants to their treatment, but others did not; the follow-up lasted from 4 to 12 weeks, depending on the study.

The studies spanned a long time period, with the oldest published in 2001 and the most recent in 2014. Medications compared included the following (listed in order of continuation medication, switched-to medication): fluoxetine, mianserin; nortriptyline, fluoxetine; venlafaxine, fluoxetine; escitalopram, duloxetine (two studies); various SSRIs, duloxetine; various SSRIs, mirtazapine; desipramine or citalopram, desipramine or citalopram.

Results
There were no statistically significant differences between patients who continued vs those who switched medications. This was true both for the primary outcome of change in depression scale score and for the secondary outcomes of response rate and remission rate.

TCPR’s Take
This is the largest and best study yet looking at whether it’s better to switch antidepressants or stay the course, and the implication is that there is no advantage to switching.

Practice implications
When patients do not respond to an antidepressant, you may be tempted to switch to another one and then rotate through your list of favorites. But given the surprising finding that switching antidepressants incurs no discernible benefit, you may want to instead consider augmentation strategies or a psychotherapy referral.