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A retrospective analysis of ketamine intravenous therapy for post-traumatic stress disorder in real-world care settings.

L. Mcinnes, Robert M. Berman, Matthew J Worley, E. Shih

Psychiatry Research August 20, 2025 DOI: 10.1016/j.psychres.2025.116689 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort study using electronic health record data Peer reviewed
Sample size 8,136
Population Outpatient psychiatric patients diagnosed with PTSD, 87% with comorbid depression
Intervention Ketamine Intravenous Therapy (KIT)
Dose 0.6-0.8 mg/kg
Measures PTSD Checklist for DSM-5 (PCL-5), Patient Health Questionnaire-9 (PHQ-9)
Topics Esketamine Ketamine PTSD
Key findings The number of ketamine intravenous therapy treatments was associated with significant reductions in PTSD and depression symptoms, with the largest improvements in the first three treatments. By the sixth treatment, model-estimated mean reductions were 22.4 points on the PCL-5 and 7.1 points on the PHQ-9, both exceeding thresholds for clinically meaningful change, though improvements diminished with additional treatments and higher later doses did not appear to meaningfully enhance symptom reduction.

Abstract

Objective: The study evaluated the effectiveness of Ketamine Intravenous Therapy (KIT) in reducing post-traumatic stress disorder (PTSD) and depression symptoms, using electronic health record data from outpatient psychiatric patients with PTSD.

Method: We analyzed data from 8,136 patients diagnosed with PTSD, 87 % (N = 7,070) of whom also had comorbid depression. Symptom severity was measured using the PTSD Checklist for DSM-5 (PCL-5) and the Patient Health Questionnaire-9 (PHQ-9). Linear mixed effects models were used to estimate changes in symptoms over time, with number of treatments as the primary predictor. Linear, quadratic, and logarithmic terms for treatment number were tested to explore different possible patterns of symptom change over time.

Results: The number of KIT treatments was associated with significant reductions in PTSD and depression symptoms. The model using a logarithmic transformation of treatment number provided the best fit to the data, suggesting diminishing improvements with additional treatments. By the 6th treatment, model-estimated mean reductions reached 22.4 points on the PCL-5 and 7.1 points on the PHQ-9, both exceeding thresholds for clinically meaningful change. The largest improvements occurred within the first three treatments, at doses of 0.6-0.8 mg/kg. While higher doses were often used in later treatments, our findings suggest that this did not appear to meaningfully enhance symptom reduction.

Conclusions: KIT is associated with reduced PTSD and depression symptoms in a community sample, with the most substantial gains occurring early in treatment. These findings support KIT as a promising treatment option for PTSD patients.

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
Combined ketamine and psychotherapy provide no additional benefit beyond ketamine alone in treating depression or PTSD: Evidence from a help-seeking sample. Help-seeking individuals with depression and/or PTSD 2025 Observational cohort n = 624
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

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