Effect of Benzodiazepines on Esketamine Nasal Spray in Patients With Major Depressive Disorder and Suicidal Ideation

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Post-hoc analyses of pooled data from the randomized, double-blind ASPIRE 1 and ASPIRE II studies were conducted to assess the effect of esketamine in adult patients with major depressive disorder and active suicidal ideation.

The following article is a part of conference coverage from Psych Congress 2020 Virtual Experience, held virtually from September 10 to 13, 2020. The team at Psychiatry Advisor will be reporting on the latest news and research conducted by leading experts in psychiatry. Check back for more from the Psych Congress 2020.


The use of benzodiazepines does not reduce or improve the rapid antidepressant efficacy of esketamine nasal spray in patients with major depressive disorder (MDD) with active suicidal ideation and intent, according to study results presented at Psych Congress 2020, held virtually September 10 to 13, 2020.

These findings were derived from post-hoc analyses of pooled data from the randomized, double-blind ASPIRE 1 (ClinicalTrials.gov Identifier: NCT03039192) and ASPIRE II (ClinicalTrials.gov Identifier: NCT03097133) studies. These analyses included a cohort of adult patients with MDD and active suicidal ideation and intent who were randomly assigned to esketamine nasal spray 84 mg twice weekly or placebo for 4 weeks. Both groups received comprehensive standard of care comprising initial hospitalization and either newly initiated or optimized oral antidepressant therapy. Efficacy and safety endpoints were examined in patients who used concomitant benzodiazepines (n=309) and in those who did not use benzodiazepines (n=142).

Both treatment groups experienced reductions in mean Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to 24 hours after their first treatment dose. A greater improvement in depressive symptoms, however, was observed in patients receiving esketamine plus standard of care vs patients receiving standard of care alone. Among patients using benzodiazepines, the between-group difference favored esketamine over placebo (difference of least squares [LS] mean, -4.3; 95% CI, -6.63 to -1.89). The between-group difference also favored esketamine in patients not taking benzodiazepines (difference of LS mean, 3.1; 95% CI, -6.62-0.45).

The reduction in the MADRS total score was greater with esketamine plus standard of care among patients not taking benzodiazepines vs those taking benzodiazepines (mean, -16.8 vs -15.8, respectively; difference of LS mean, 1.1; 95% CI, -2.24-4.45). In the esketamine group, the incidence of sedation was higher among patients who used vs did not use benzodiazepines (8.1% vs 1.3%, respectively). The incidence of dissociation was similar between those who used vs did not use benzodiazepines (32.0% vs 26.6%).

Limitations of the research include analyses being conducted on a post hoc basis and the fact that the ASPIRE studies did not allow concomitant benzodiazepine use within 8 hours of esketamine dosing or within 8 hours of primary efficacy assessment.

Disclosure: This clinical trial was supported by Janssen Research & Development, LLC. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Diekamp B, Borentain S, Fu D, et al. Effect of benzodiazepines on esketamine nasal spray for treating patients with major depressive disorder with active suicidal ideation and intent. Presented at: Psych Congress 2020 Virtual Experience; September 10-13, 2020. Poster 142.