Combining Ketamine Infusions and Written Exposure Therapy for Chronic PTSD: An Open-Label Trial.
Adriana Feder, Oneysha Brown, Sarah B Rutter, Leah Cahn, Jessica R Overbey, Saren H Seeley, Alex Yu, Philip A Bonanno, Rachel A Fremont, Andrew A Delgado, Manish K Jha, Sara Costi, Rachel Yehuda, Daniela Schiller, Robert H Pietrzak, Dennis S Charney, Denise M Sloan, James W Murrough
The Journal of clinical psychiatry April 2, 2025 DOI: 10.4088/JCP.24m15622 via PubMed
Summary
AI-generated from the abstractCombining six ketamine infusions with a brief exposure-based psychotherapy, written exposure therapy (WET), produced large and durable reductions in PTSD symptoms for patients with chronic, severe PTSD. In an open-label trial, 13 of 14 patients completed treatment. PTSD symptom severity, measured by the CAPS-5, dropped from an average of 41.6 before treatment to 20.8 at 12 weeks, a large-magnitude improvement. Nine patients (69%) were treatment responders, and eight (61.5%) maintained improvement up to six months. The authors suggest the combined treatment may be effective but call for larger randomized controlled trials to confirm efficacy and synergy.
Study at a glance
| Characteristics | Open-label clinical trial Randomized Peer reviewed |
|---|---|
| Sample size | 14 |
| Population | Patients with chronic posttraumatic stress disorder and high-moderate to severe symptom levels |
| Interventions | Ketamine Written exposure therapy (WET) |
| Dose | 0.5 mg/kg |
| Duration | 2-week intervention, 12-week primary endpoint, up to 6-month follow-up |
| Keywords | PTSD-Treatment Psychedelic-therapy Ketamine-therapy Mental-health-research |
| Registration | NCT04889664 |
| Key finding | Combining six ketamine infusions with written exposure therapy was associated with large-magnitude and durable reductions in PTSD symptoms in patients with chronic, severe PTSD. |
Abstract
Objective: This open-label clinical trial examined the preliminary efficacy of combining a course of 6 ketamine infusions with a brief, evidence-based exposure-based psychotherapy-written exposure therapy (WET)-in patients with chronic posttraumatic stress disorder (PTSD). Methods: The trial was conducted between June 2021 and October 2023. Patients with chronic PTSD and high-moderate to severe symptom levels received 6 intravenous ketamine infusions (0.5 mg/kg), 3 times a week for 2 consecutive weeks, plus 5 WET sessions over 2 weeks, beginning after the first 4 infusions and administered on different days than infusion days. The primary outcome was change in the Clinician Administered PTSD Scale for DSM-5 (CAPS-5) scores from baseline (before the first infusion) to 12 weeks from start of WET ("Week 12"). Results: Fourteen eligible patients began treatment, and 13 completed all infusions and WET. The combined treatment was associated with large-magnitude improvement in PTSD symptom severity from baseline (mean CAPS 5 = 41.6 [SD = 6.2]) to Week 12 (CAPS 5 = 20.8 [14.8], Cohen d [95% CI] = 1.9 [1.0-2.8], P < .001). Nine (69%) patients were treatment responders (≥30% improvement on the CAPS-5). Response was rapid and also durable in 8 (61.5%) patients, assessed up to 6 months from baseline. Conclusions: Preliminary findings from this open-label clinical trial suggest that the combined treatment may yield large magnitude and durable reductions in PTSD symptoms for patients with more severe chronic PTSD. Large-scale randomized controlled trials are needed to determine the efficacy and potential synergistic effect of this promising combined treatment in this patient population. Trial Registration: ClinicalTrials.gov identifier: NCT04889664.