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Combined ketamine and psychotherapy provide no additional benefit beyond ketamine alone in treating depression or PTSD: Evidence from a help-seeking sample.

Tyler M Moore, Kathryn Walker, Emma Tung, Adam R. Teed, Franz Hell, Sivan Kinreich, Rex E. Jung, Fadi Abdel, Russell W. Hanson, Shobi S Ahmed

Journal of Affective Disorders July 15, 2025 DOI: 10.1016/j.jad.2025.04.041 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort Peer reviewed
Sample size 624
Population Help-seeking individuals with depression and/or PTSD
Interventions Ketamine alone Ketamine plus psychotherapy
Duration 4-14 treatment sessions within a 30- or 180-day period
Topics Depression Ketamine Esketamine PTSD
Keywords Post-traumatic stress Psychotherapy Mental health Depression therapy Ketamine treatment PTSD Research Clinical trials
Citations 8
Key findings Adding psychotherapy to ketamine treatment did not significantly improve depression or PTSD symptom trajectories compared to ketamine alone over 30 or 180 days.

Abstract

Depression and PTSD are prevalent psychiatric conditions that often co-occur and significantly impact quality of life. Ketamine has emerged as a promising rapid-acting treatment for both conditions, while traditional treatments like psychotherapy typically require weeks to show effects. This study investigated whether combining ketamine with psychotherapy produces greater symptom improvement compared to ketamine alone. We analyzed overlapping samples of N = 202, N = 470, and N = 624 help-seeking individuals (all samples ∼60 % female, mean age ∼ 42 years) who received either ketamine alone (KET) or ketamine plus psychotherapy (KET+PSY) across 4-14 treatment sessions within a 30- or 180-day period. Depression symptoms were measured using the PHQ-9, and PTSD symptoms were assessed using the PCL-5. Trajectories of symptom change were analyzed using generalized additive mixed-effects models, controlling for baseline symptoms, demographics, and treatment intervals. Both treatment groups showed substantial improvement in depression and PTSD symptoms, with similar patterns of rapid initial decline followed by stabilization. Contrary to our hypothesis, we found no significant differences in symptom trajectories between the KET and KET+PSY groups. Exploratory analyses revealed non-significant but notable patterns where younger females showed better outcomes with combined treatment, while older males showed better outcomes with ketamine alone. These findings suggest that ketamine's therapeutic effects may be robust enough that additional psychotherapy during the acute treatment phase does not significantly enhance 30-day (and possibly 180-day) outcomes. However, longer-term benefits of combined treatment and potential demographic-specific treatment responses warrant further investigation. These results have important implications for treatment planning and resource allocation in clinical settings.

Comparable studies

Other observational and cohort studies on ketamine for PTSD, most cited first.

Study Year Design Participants
Impact of oral ketamine augmentation on hospital admissions in treatment-resistant depression and PTSD: a retrospective study. Outpatients with treatment-resistant depression and PTSD 2018 Retrospective review n = 37
Ketamine-Assisted Psychotherapy Provides Lasting and Effective Results in the Treatment of Depression, Anxiety, and Post-Traumatic Stress Disorder at 3 and 6 Months: Findings from a Large Retrospective Effectiveness Study. Adults with a history of major depressive disorder, generalized anxiety disorder, or... 2024 Retrospective effectiveness study n = 346
Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm. Outpatients with elevated PTSD Checklist for DSM-5 scores 2025 Retrospective study n = 117
Ketamine treatment effects on DNA methylation and Epigenetic Biomarkers of aging Individuals with major depressive disorder or posttraumatic stress disorder 2024 Observational cohort n = 20
Ketamine Assisted EMDR Therapy™ for PTSD: investigating the synergistic effects of pharmacotherapy and psychotherapy Clients with PTSD in a private psychotherapy practice 2025 Retrospective clinical chart review n = 8

Citations in the library

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Depression Ketamine Esketamine PTSD

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Ketamine for PTSD Ketamine for depression