Switching Antidepressants During Nonresponse May Be Ineffective

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Adults with major depressive disorder who are nonresponsive to treatment may not benefit from switching antidepressant.
Adults with major depressive disorder who are nonresponsive to treatment may not benefit from switching antidepressant.

One of the biggest challenges in assessing the treatment of major depression is antidepressant effectiveness. All antidepressants share a high rate of nonresponse, which often leads clinical practitioners to switch the antidepressant they have prescribed.

Observational studies often show improvement when nonresponders switch to a second antidepressant. However, it is impossible to conclusively determine whether improvement results from this change, from a placebo effect, or from natural illness course. In order to answer the question of whether switching to a new antidepressant is better than continuation of the first antidepressant, psychiatrists at Schlosspark-Clinic in Berlin, Germany, performed a systematic literature review and meta-analysis of studies that compared continuation of the initial antidepressant with switching to a new one.

This study — an update of a similar analysis from May 2007 — computed standardized mean differences (SMDs) from difference in depression rating scale scores or difference in change in scores at study endpoint, which was no longer than 12 weeks' continuation. Data analyses were performed using Comprehensive Meta-Analysis (Version 2) according to procedures outlined in the Cochrane Collaboration Handbook, and random effects models were applied.

None of the 4 studies fulfilling strict inclusion criteria reported a statistically significant advantage of switching the antidepressant over continuation with the so far ineffective medication, but 1 study found continuation to be superior to switching (SMD = −0.95 [95% CI, −1.51 to −0.38], P =.001). The meta-analytic estimate of all 4 studies combined demonstrated that switching was less effective than continuation, albeit without reaching statistical significance and with considerable heterogeneity. (SMD = −0.17 [95% CI, −0.59 to 0.26], P =.45; I2 =77.8%). The researchers allowed dose increase in 4 additional studies in a broad analysis; results included no significant difference between the 2 strategies of switching and continuation.

The meta-analysis offered no evidence that switching to a new antidepressant is more effective than continuation of the original antidepressant. Outcomes consistently resulted in small and statistically nonsignificant summary effects. As a result, switching cannot be ruled a best practice in treatment of major depressive disorder, supporting the initial meta-analysis from 2007.

Still, the concept of switching antidepressants requires further investigation. “There is an urgent need for further controlled studies on switching,” the authors of this study wrote, “as nonresponse to antidepressants continues to be a serious clinical problem. Physicians should be cautious with switching antidepressants and prefer one of several treatment strategies better evaluated in nonresponders to antidepressant treatment.”


Bschor T, Kern H, Henssler J, Baethge C. Switching the antidepressant after nonresponse in adults with major depression: a systematic literature search and meta-analysis. J Clin Psychiatry. 2016; doi.10.4088/JCP.16r10749. 

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