Esketamine Nasal Spray Effective for Treatment-Resistant Depression

A patient is using a nasal spray indoor
Adult patients with treatment-resistant depression showed a favorable improvement in symptoms after a course of esketamine twice-weekly for 28 days.

The use of adjunctive esketamine nasal spray was found to be safe and effective for patients with treatment-resistant depression, according to study results published in the American Journal of Psychiatry.

Researchers conducted a double-blind active-controlled randomized study of 223 individuals with treatment-resistant depression (62% women, mean age 45.7). Participants were randomly assigned to receive either an antidepressant plus esketamine nasal spray (n=114) or placebo nasal spray plus antidepressant (n=109) for a total of 28 days. The nasal spray was dosed at 56 mg or 84 mg twice weekly for the treatment phase. The primary outcome measured was the change in Montgomery-Asberg Depression Rating Scale score from start of therapy to 28 days.

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After analysis, the researchers found that the difference in Montgomery-Asberg Depression Rating Scale score in participants treated with an antidepressant plus esketamine was significantly higher than participants with antidepressant plus placebo after 28 days (difference of least square means, −4.0;  95% CI, −7.31 to −0.64; P =.020).

With respect to safety, the most frequently seen adverse effects (nausea, dizziness, dysgeusia, dissociation, and vertigo) occurred more often in the antidepressant plus esketamine group vs the antidepressant plus placebo group.

One key limitation of the study was the exclusion of individuals with major psychiatric comorbidities.

“The study supports the efficacy and safety of esketamine nasal spray as a rapidly acting antidepressant for patients with treatment-resistant depression,” the researchers wrote.

Several authors are the employees of Janssen Research and Development and hold company equity. See source for complete funding and disclosure information.


Popova V, Daly EJ, Trivedi M, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019;176(6):428-438.