Combining Ketamine Infusions and Written Exposure Therapy for Chronic PTSD: An Open-Label Trial.

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.