Optimal Strategy for Switching Antidepressants Remains Unknown

While switching antidepressants is an appropriate strategy to use if there is a minimal response to an initial antidepressant, the optimal approach to switching is unknown and more research is needed.

Switching antidepressants is recommended if the response to the previous antidepressant is minimal, but more research is needed to determine the optimal approach, according to a recent article published in the Journal of Affective Disorders.

This research was conducted by clinical and academic experts in mood disorders from Australia and New Zealand, who discussed switching antidepressants in the treatment of depression and completed a literature review. Switching antidepressants is widely recommended when an inadequate response is seen in an initial medication, but what defines an inadequate response remains unclear. Changes in symptoms are often difficult to gauge and many medications have extended periods before they become effective. The correct duration of treatment remains unclear as well.

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The panel agreed that limited improvement (<20% reduction in a depression rating scale score) after 2 to 3 weeks of treatment predicts subsequent nonresponse. Furthermore, when switching antidepressants, switching within class is recommended if side effects are present, unless the side effect relates to the whole class of antidepressants. In this case, switching to another class is recommended. The risks and benefits of switching within class vs switching out of class are unclear. Clinical characteristics of the depressive episode should be considered as switching studies have not considered type of depression. After nonresponse or partial response, the recommended strategy is to cross-taper the antidepressants. Patients who fail to respond to the new antidepressant will require a thorough review.

Study investigators concluded that little evidence exists to suggest what the best strategies for switching antidepressants are, but that “While there is limited research evidence, there is sufficient empirical evidence to recommend switching as an initial strategy for antidepressant non-response once the dose of the initial agent is optimized.” 

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Boyce P, Hopwood M, Morris G, et al. Switching antidepressants in the treatment of major depression: when, how and what to switch to? J Affect Disord. 2019;261:160-163.