SSRI Dose Increase Not Recommended for Antidepressant Treatment Failure

Investigators examined whether a dose increase of antidepressants is an effective treatment strategy for antidepressant treatment failure.

Individuals with major depressive disorder and initial antidepressant treatment failure should not be administered increased doses of most selective serotonin reuptake inhibitors (SSRIs), according to a study published in The Journal of Clinical Psychiatry. Further research is needed to investigate dose increase with other antidepressants, lengths of therapy, and types of patient groups.

Study researchers included 1273 individuals from 9 studies in this meta-analysis, whose PROSPERO Registration is CRD42017058389. SSRIs were used in all studies and maprotiline was used in 1 study. Antidepressant dose increase showed a favorable standardized mean difference of 0.053, a statistically nonsignificant summary effect margin (95% CI, -0.143 to 0.248). Sensitivity, subgroup, and secondary outcome analyses gave similar results.

This systematic review included 9 out of 1780 studies drawn from CENTRAL, Embase, PubMed, and PsycINFO, which were initially screened using keywords for depression, randomized controlled trials, and dose increase. The selected randomized controlled trials included participants with a unipolar depression diagnosis, a trial of antidepressants at least 3 weeks in length that ended in antidepressant treatment failure, an increase in dose, and a control group that continued the dose. Data were independently collected by 2 authors according to the Cochrane Handbook for Systematic Reviews, and random effects models were used in evaluation.

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The study researchers conclude that “[with] clinically and statistically nonsignificant effect estimates, there is evidence from [randomized controlled trials] against increasing the dose of SSRIs (with the possible exception of citalopram) in adult patients with major depression and [antidepressant treatment failure]. Dose increase with other antidepressants (eg, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors) and in other patient groups (minor depression, children and adolescents) or after long periods of first-line antidepressant therapy (ie, 8 weeks) have not been or not been sufficiently studied and, at this time, cannot be recommended in clinical practice.”


Rink L, Braun C, Bschor T, Henssler J, Franklin J, Baethge C. 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 trialsJ Clin Psychiatry. 2018; 79(3).