Efficacy and safety of intravenous ketamine treatment in Japanese patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial

Psychiatry Clin Neurosci. 2024 Dec;78(12):765-775. doi: 10.1111/pcn.13734. Epub 2024 Aug 30.

Abstract

Aim: Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD.

Methods: In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score.

Results: Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (-8.1 ± 10.0 vs -2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (-9.1 ± 10.2 vs -2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score.

Conclusion: Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations.

Keywords: ethnicity; ketamine; major depressive disorder; repeated doses; treatment‐resistant depression.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous*
  • Adult
  • Antidepressive Agents* / administration & dosage
  • Antidepressive Agents* / adverse effects
  • Antidepressive Agents* / pharmacology
  • Depressive Disorder, Treatment-Resistant* / drug therapy
  • Double-Blind Method
  • East Asian People
  • Female
  • Humans
  • Japan
  • Ketamine* / administration & dosage
  • Ketamine* / adverse effects
  • Ketamine* / pharmacology
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Treatment Outcome

Substances

  • Ketamine
  • Antidepressive Agents