Long-term follow-up of participants in ketamine clinical trials for mood disorders

J Affect Disord. 2024 Jul 15:357:134-137. doi: 10.1016/j.jad.2024.04.062. Epub 2024 Apr 22.

Abstract

Background: Participants who received ketamine at the NIMH were among the first to receive ketamine for depression in controlled clinical trials, providing a unique opportunity to assess long-term outcomes. This analysis evaluated the relationship between participating in a ketamine clinical trial and subsequent ketamine/esketamine use after leaving the research setting.

Methods: Participants seen within the NIMH Experimental Therapeutics and Pathophysiology Branch from 2002 to 2022 (n = 1000) were contacted for follow-up assessment. Participants reported whether they had used ketamine/esketamine, sought non-prescribed ketamine, attempted suicide, or been psychiatrically hospitalized since discharge. Information regarding their recent depressive symptoms, dissociative symptoms, and hallucinations was also collected.

Results: Of the 203 participants in follow-up assessments (55 % female, average time since leaving NIMH = 9.04 years), 52 (25.6 %) had originally received ketamine at the NIMH, and the rest had participated in non-ketamine studies. Individuals who had received ketamine at the NIMH were more likely to have received ketamine/esketamine post-discharge than those who did not receive ketamine at the NIMH (OR = 0.25, p < .001). Participants who reported using ketamine/esketamine post-discharge reported more depressive symptoms than those who had not (p < .001). Receiving ketamine at the NIMH was not associated with differences in suicide attempts, psychiatric hospitalizations, dissociation, hallucinations, or attempt to obtain non-prescribed ketamine.

Limitations: Low follow-up study participation rate; varying time since discharge.

Conclusions: Participants who received ketamine in an NIMH clinical trial were more likely to receive ketamine/esketamine post-discharge, but none reported symptoms indicating abuse. Results underscore the critical need for long-term follow-up of individuals receiving these and other rapid-acting antidepressants.

Clinical trials identifier: NCT04877977.

Keywords: Clinical trials; Depression; Esketamine; Ketamine.

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use
  • Dissociative Disorders / drug therapy
  • Female
  • Follow-Up Studies
  • Hallucinations / drug therapy
  • Humans
  • Ketamine* / therapeutic use
  • Male
  • Middle Aged
  • Mood Disorders / drug therapy
  • Suicide, Attempted*

Substances

  • Ketamine
  • Esketamine
  • Antidepressive Agents

Associated data

  • ClinicalTrials.gov/NCT04877977