Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm.

Intravenous ketamine administered in a supportive environment with preparation, intention-setting, integration sessions, eye shades, and evocative music—paralleling psychedelic therapy—was associated with large reductions in PTSD symptoms. In a retrospective sample of 117 outpatients, mean PCL-5 scores dropped from 52.54 to 28.78, with 75% showing clinically meaningful improvement and 62% suggesting remission. No serious adverse events occurred, and concomitant psychotherapy was a significant moderator. The findings suggest that environmental factors may account for variation in previous ketamine studies and that this approach may be a promising option for PTSD unresponsive to other treatments.

Study at a glance

Abstract

Traditional treatments for post-traumatic stress disorder (PTSD) often show limited success with high dropout. Ketamine, an N-methyl-D-aspartate antagonist known for rapid antidepressant effects, has decreased PTSD symptoms in some studies but not in others. Administering ketamine in ways that parallel psychedelic-assisted treatments-including preparatory, integration, sensory immersion, and psychotherapy sessions-could decrease PTSD symptoms meaningfully. A retrospective sample of 117 screened outpatients with elevated PTSD Checklist for DSM-5 (PCL-5) scores received intravenous ketamine in supportive environments. The protocol included preparation, intention-setting, and integration sessions accompanying at least six administrations. Administration sessions included eye shades and evocative music paralleling typical psychedelic therapy trials. Mean PCL scores decreased from 52.54 (SD = 12.01) to 28.78 (SD = 16.61), d = 1.64. Patients tolerated treatment well, with no serious adverse events. Covariates, including age, gender, days between PCL assessments, number of psychiatric medications, and suicidal ideation were not significant moderators; concomitant psychotherapy did reach significance, d = 0.51. Of the 117 patients' final PCL scores, 88 (75.21%) measures suggested clinically meaningful improvement and 72 (61.54%) suggested remission of PTSD symptoms. Intravenous ketamine in supportive environments, with hallmarks of psychedelic therapy, preceded large reductions in PTSD symptoms. These results highlight ketamine's potential when delivered in this manner, suggesting environmental factors might account for some variation seen in previous work. Given the molecule's cost, minimal interaction with other psychiatric medications, and legal status, intravenous ketamine in a psychedelic paradigm may be a promising option for PTSD unresponsive to other treatments.