Author:

Keywords:

esketamine, resistant depression, Science & Technology, Life Sciences & Biomedicine, Neurosciences, Psychiatry, Neurosciences & Neurology, Efficacy, Esketamine, Intravenous, Safety, TRD, Treatment-resistant depression, STAR-ASTERISK-D, D-ASPARTATE ANTAGONIST, MAJOR DEPRESSION, HEALTHY-VOLUNTEERS, KETAMINE, ANTIDEPRESSANT, TRIAL, PHARMACOKINETICS, PERCEPTION, DISORDERS, Adolescent, Adult, Depressive Disorder, Treatment-Resistant, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Infusions, Intravenous, Ketamine, Male, Middle Aged, Young Adult, 06 Biological Sciences, 11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences, 31 Biological sciences, 32 Biomedical and clinical sciences, 52 Psychology

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.