In a study published in the Journal of Clinical Psychiatry, the investigators did not recommend increasing antidepressant dosage in response to treatment failure, after analyses of dose increase regimens appeared to reveal insignificant changes in effect size.

Some surveys have demonstrated that a dose increase is the prevailing reaction to a lack of response to antidepressant treatment. Other common recommended practices include switching to a different antidepressant, combining two or more antidepressants, or augmenting treatment with antipsychotics.

The investigators identified 9 studies comprising 1273 adult patients via the CENTRAL, PubMed, Embase, and PsycINFO databases. They included randomized, controlled trials in which patients with unipolar depression who had not responded to antidepressant treatment were assigned to dose increase schedules or continued-dose control groups. All studies examined selective serotonin reuptake inhibitors, with 1 study also reporting on maprotiline.

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Compared with a continued dose in accordance with a patient’s initial prescription, an increased dose was not shown to be more effective, with a negligible standardized mean difference of 0.053 (95% CI, −0.143 to 0.248). In a similar fashion, secondary outcome analyses found a nonsignificant odds ratio of 1.124 for antidepressant response and depression remission.

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The researchers pointed out the considerable heterogeneity of their main analyses, although subgroup and sensitivity analyses also supported their findings. They also cautioned that the findings might not generalize to other types of antidepressants.

As this and previous research on dose increase strategies have produced inconsistent findings, the investigators recommended clinicians consider other responses to antidepressant treatment failure, at least for selective serotonin reuptake inhibitors. The effect of a dose increase in antidepressants other than selective serotonin reuptake inhibitors, they stated, warrants future examination.


Rink L, Braun C, Bschor T, et al.  Dose increase versus unchanged continuation of antidepressants after initial antidepressant treatment failure in patients with major depressive disorder: a systematic review and meta-analysis of randomized, double-blind trials. J Clin Psychiatry. 2018;79(3):17r11693.

This article originally appeared on Psychiatry Advisor