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

People who received ketamine for depression in early clinical trials at the National Institute of Mental Health (NIMH) were more likely to obtain ketamine or esketamine after leaving the research setting. Among 203 former participants followed up an average of nine years later, 25.6% had originally received ketamine at the NIMH. Those who had received ketamine were significantly more likely to have used ketamine or esketamine afterward. However, receiving ketamine at the NIMH was not linked to higher rates of suicide attempts, psychiatric hospitalizations, dissociation, hallucinations, or attempts to obtain non-prescribed ketamine. Participants who used ketamine or esketamine after discharge reported more depressive symptoms. No symptoms indicating abuse were reported. The findings highlight the need for long-term monitoring of patients receiving rapid-acting antidepressants.

Study at a glance

Abstract

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. 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. 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. Low follow-up study participation rate; varying time since discharge. 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. NCT04877977.