
Is Esketamine Augmentation a Win for Depression?
Last year, the FDA approved esketamine, a rapidly acting adjunctive intranasal therapy for treatment-resistant depression. Now, researchers are exploring its efficacy in major depressive disorder.
RESEARCH UPDATE
How well does
The primary outcome was the standardized mean difference (SMD) in change in depression scores between adjunctive esketamine and placebo. Secondary outcomes were the relative risk for response and remission between these two groups. The authors analyzed the data using a random effects meta-analysis. They calculated a quality score for each included trial and assessed for publication bias with a funnel plot and Egger’s test.
The authors identified 8 articles for full-text review from PubMed, of which 2 were included in the meta-analysis. They also identified 5 additional completed clinical trials from scientific meetings, of which 3 were included. Thus, the meta-analysis comprised 5 trials (with 11 esketamine-placebo comparator arms), all of which used the MADRS as their primary outcome measure. The pooled sample included 774 patients with MDD. The authors found that adjunctive intranasal esketamine was associated with significantly greater MADRS score reduction than placebo with a small-to-medium effect size (SMD=0.36). Intranasal esketamine was also associated with a significantly increased likelihood of response (RR=1.40) and remission (RR=1.45).
Papakostas and colleagues concluded that augmentation of antidepressants with intranasal esketamine was significantly more effective than placebo for both continuous and categorical measures of depression severity in patients with MDD. The reduction in MADRS scores was approximately 2-5 points lower in patients treated with intranasal esketamine versus placebo. The number needed to treat for response and remission was 6 and 7, respectively. The authors noted that treatment effects may be larger for repeated intravenous ketamine than for intranasal esketamine, but said further investigation is needed. Limitations include the possibility of unpublished or unpresented studies, non-standard definitions of treatment-resistant depression, and different study durations.
The bottom line
The authors found meta-analytic evidence for the efficacy of augmentation with intranasal esketamine (versus placebo) in the acute phase of treatment for MDD.
Disclosures:
Dr Miller is Associate Professor, Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA. He is the Schizophrenia Section Chief for Psychiatric Times. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, the Brain and Behavior Research Foundation, and the Stanley Medical Research Institute.
References:
1. FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic. Press release. US Food & Drug Administration website. March 5, 2019. https://www.fda.gov/news-events/press-announcements/fda-approves-new-nasal-spray-medication-treatment-resistant-depression-available-only-certified
2. Papakostas G, Salloum NC, Hock RS, et al. Efficacy of esketamine augmentation in major depressive disorder: a meta-analysis. J Clin Psychiatry. 2020;81:4.
Newsletter
Receive trusted psychiatric news, expert analysis, and clinical insights — subscribe today to support your practice and your patients.