Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm
In a real-world sample of 117 treatment‑resistant PTSD outpatients, intravenous ketamine delivered within a supportive “psychedelic” paradigm (preparation, music, integration and psychotherapy) was associated with large, rapid and sustained reductions in PCL‑5 scores (mean 52.5 → 28.8, d = 1.64), with 75% showing clinically meaningful improvement and 62% meeting criteria for remission. Treatment was well tolerated with no serious adverse events, suggesting this delivery model may enhance ketamine’s effectiveness for refractory PTSD.
Abstract
Background
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 others. Administering ketamine in ways that parallel psychedelic-assisted treatments—including preparatory, integration, sensory immersion, and psychotherapy sessions—could decrease PTSD symptoms meaningfully.
Methods
A 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.
Results
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.
Conclusion
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.
Research Summary of 'Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm'
Introduction
Post-traumatic stress disorder (PTSD) is a chronic, disabling condition characterised by intrusive memories, avoidance, negative mood and heightened arousal. Conventional therapies—trauma-focused psychotherapies and pharmacotherapy (primarily SSRIs)—have substantial limitations: many patients do not achieve remission, dropout rates can be high, and pharmacological benefits often take weeks to appear. Interest in rapid-acting treatments has therefore increased, and ketamine, an N-methyl-D-aspartate (NMDA) antagonist with rapid antidepressant effects at subanaesthetic doses, has been investigated for PTSD with mixed findings across trials. Macconnel and colleagues set out to examine clinical outcomes after delivering intravenous ketamine within a treatment model that intentionally incorporated elements common to psychedelic-assisted therapies—psychological preparation, sensory immersion (music and eye shades), integration sessions and supportive staffing—at a real‑world clinic. The study reports a retrospective chart review of patients treated at a single clinic and aims to assess change in PTSD symptoms measured by the PCL-5 and to explore moderators such as concomitant psychotherapy, demographic factors and prior medication trials in this psychedelic-style delivery context.
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Study Details
- Study Typeindividual
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- APA Citation
MacConnel, H. A., Earleywine, M., & Radowitz, S. (2024). Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm. https://doi.org/10.31234/osf.io/78m96
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