The efficacy and safety of adjunctive intranasal esketamine treatment in major depressive disorder: a systematic review and meta-analysis

Expert Opin Drug Saf. 2022 Jun;21(6):841-852. doi: 10.1080/14740338.2022.2058488. Epub 2022 Apr 6.

Abstract

Introduction: Intranasal (IN) esketamine represents an innovative treatment for individuals with treatment resistant depression and depression with suicidal ideation and behavior. Herein, we synthesize extant long-term studies (≥ 4 weeks) regarding this treatment.

Research design and methods: The interventional studies of IN esketamine in patients with depression having a study period of at least four weeks were included for our synthesis. A meta-analysis was undertaken for the efficacy and safety parameters of adjunctive IN esketamine vs IN placebo with an oral antidepressant. The data excluded from meta-analysis were synthesized narratively.

Results: After pooling data from seven randomized controlled trials, treatment with adjunctive IN esketamine vs IN placebo was safe overall, and more effective at decreasing depressive symptoms (d = -0.239; 95%CI = -0.335,-0.142;p < 0.0001), with higher response (RR = 1.221; 95% CI = 1.055,1.428; p = 0.017) and remission (RR = 1.366; 95% CI = 1.182,1.578; p < 0.0001) rates. The year-long trials showed that treatment with adjunctive IN esketamine led to lower relapse rates with no considerable long-term side effects.

Conclusion: Intranasal esketamine was demonstrated to be safe, well tolerated, and rapidly effective in individuals with treatment resistant depression, suicidal ideation, and suicidal behavior.

Keywords: Depression; antidepressants; bipolar disorder; esketamine; glutamate; ketamine; mood disorders; rapid-acting treatments; suicide.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antidepressive Agents
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Treatment-Resistant* / drug therapy
  • Humans
  • Ketamine* / adverse effects

Substances

  • Antidepressive Agents
  • Esketamine
  • Ketamine