Long-Term Effects of Repeated Ketamine Infusions for Comorbid PTSD and Treatment-Resistant Depression


Objective: This study investigated the effectiveness, safety, and lasting effects of repeated ketamine infusions for treating comorbid posttraumatic stress disorder (PTSD) and treatment-resistant depression (TRD) in a group of veterans.

Methods: Fifteen individuals diagnosed with both DSM-5-defined PTSD and DSM-IV-defined major depressive disorder received six intravenous ketamine infusions (0.5 mg/kg) on Mondays, Wednesdays, and Fridays over a 12-day period from May 2015 to June 2016. Symptom data were collected before and 24 hours after each infusion, as well as weekly for 8 weeks following the final infusion.

Results: Significant improvements in symptoms were observed for both PTSD and depression, with substantial effect sizes (average decrease in PTSD Checklist for DSM-5 score = 33.3 points [95% CI, 23.0-43.5 points], P < .0005, adjusted Cohen’s d [d’] = 2.17; average decrease in Montgomery-Asberg Depression Rating Scale score = 26.6 points [95% CI, 23.0-30.2 points], P < .0005, d’ = 4.64). The remission rate for PTSD was 80.0%, and the response rate for TRD was 93.3%. Participants who achieved PTSD remission post-infusion series (n = 12) had a median relapse time of 41 days. Similarly, participants whose depression responded to the infusions (n = 14) had a median relapse time of 20 days. Repeated ketamine infusions led to temporary increases in dissociative symptoms, but no participant reported worsening PTSD symptoms during the study.

Conclusions: This pioneering open-label study of repeated ketamine infusions in a comorbid population demonstrated rapid and sustained improvements in PTSD and depression symptoms. The findings suggest that repeated ketamine treatments are safe and potentially effective for individuals with comorbid PTSD and TRD.

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