Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study
Jaskaran Singh, Maggie Fedgchin, Ella Daly, Liwen Xi, Caroline Melman, Geert De Bruecker, Andre Tadic, Pascal Sienaert, Frank Wiegand, Husseini Manji, Wayne C. Drevets, Luc Van Nueten
Biological Psychiatry November 4, 2015 DOI: 10.1016/j.biopsych.2015.10.018 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Double-blind Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Patients with treatment-resistant depression |
| Intervention | Esketamine |
| Dose | 0.20 mg/kg or 0.40 mg/kg |
| Duration | 40-minute infusion on day 1, with assessment on day 2 |
| Topics | Depression Esketamine |
| Citations | 466 |
| Key findings | Both 0.20 mg/kg and 0.40 mg/kg doses of intravenous esketamine produced rapid and significant antidepressant effects compared to placebo in treatment-resistant depression, with the lower dose potentially offering better tolerability. |
Abstract
Background: The purpose of this study was to assess the efficacy and safety and to explore the dose response of esketamine intravenous (IV) infusion in patients with treatment-resistant depression (TRD).
Methods: This multicenter, randomized, placebo-controlled trial was conducted in 30 patients with TRD. Patients were randomly assigned 1:1:1 to receive an IV infusion of .20 mg/kg or .40 mg/kg esketamine or placebo over 40 minutes on day 1. The primary end point was change in Montgomery-Åsberg Depression Rating Scale total score from day 1 (baseline) to day 2. Nonresponders who received placebo on day 1 were randomly assigned again 1:1 to IV esketamine .20 mg/kg or .40 mg/kg on day 4. Secondary efficacy and safety measures were also evaluated.
Results: Of the enrolled patients, 97% (29 of 30) completed the study. The least squares mean changes (SE) from baseline to day 2 in Montgomery-Åsberg Depression Rating Scale total score for the esketamine .20 mg/kg and .40 mg/kg dose groups were -16.8 (3.00) and -16.9 (2.61), respectively, and showed significant improvement (one-sided p = .001 for both groups) compared with placebo (-3.8 [2.97]). Esketamine showed a rapid (within 2 hours) and robust antidepressant effect. Treatment-emergent adverse events were dose dependent. The most common treatment-emergent adverse events were headache, nausea, and dissociation; the last-mentioned was transient and did not persist beyond 4 hours from the start of the esketamine infusion.
Conclusions: A rapid onset of robust antidepressant effects was observed in patients with TRD after a 40-minute IV infusion of either .20 mg/kg or .40 mg/kg of esketamine. The lower dose may allow for better tolerability while maintaining efficacy.
In the evidence
This study is part of the evidence base for 3 syntheses in the library. Here is how each one recorded it.
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Both 0.20 mg/kg and 0.40 mg/kg intravenous esketamine produced rapid, significant antidepressant effects versus placebo, with dose-dependent adverse events.
Synthesized
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Both 0.20 mg/kg and 0.40 mg/kg intravenous esketamine produced rapid, significant antidepressant effects versus placebo, with dose-dependent adverse events.
Synthesized
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State of the evidence: Esketamine Supports
Both 0.20 mg/kg and 0.40 mg/kg doses of intravenous esketamine produced rapid and significant antidepressant effects compared to placebo in treatment-resistant depression, with the lower dose potentially offering better tolerability.
Synthesized
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.