Oral ketamine, when added to sertraline, is associated with significant improvements in depressive symptoms compared with placebo, according to findings from a double-blind, placebo-controlled trial published in the Journal of Affective Disorders.

Investigators assigned a total of 81 patients with major depressive disorder (MDD) to receive 50 mg/day oral ketamine plus 150 mg/day sertraline (n=41) or 50 mg/day placebo plus 150 mg/day sertraline (n=40). There were no differences between the 2 groups in terms of baseline MDD duration or baseline Hamilton Depression Rating Scale scores. Hamilton Depression Rating Scale score changes from baseline were compared at 2, 4, and 6 weeks in both groups following treatment initiation.

A significantly greater proportion of patients with MDD randomly assigned to receive ketamine experienced early improvements in depressive symptoms compared with those assigned to receive placebo (85.4% vs 42.5%, respectively; odds ratio [OR], 7.89; 95% CI, 2.70-22.98; P <.001).

Continue Reading

A greater proportion of patients randomly assigned to ketamine vs placebo responded to therapy at week 6 (85.4% vs 57.5%, respectively; OR, 4.31; 95% CI, 1.48-12.55; P =.005). The number of patients with disease remission, however, did not differ between the 2 groups (22.0% vs 15.0%; OR, 1.59; 95% CI, 0.51-4.98; P =.42). Side effects were minimal, did not differ between groups, and were mild in intensity.

Related Articles

The short duration of follow-up (6 weeks) prevented the investigators from determining whether potential long-term adverse effects of ketamine negated its observed short-term advantages. Longer-term trials may be helpful to determine the treatment’s sustainability in patients with MDD.

Investigators of this study suggest that the “short lag between ketamine administration and alleviation of depressive symptoms makes ketamine a good option” as an adjunct to a sertraline antidepressant regimen.


Arabzadeha S, Hakkikazazia E, Shahmansouri N, et al. Does oral administration of ketamine accelerate response to treatment in major depressive disorder? Results of a double-blind controlled trial [published online February 21, 2018]. J Affect Disord. doi: 10.1016/j.jad.2018.02.056