In a randomized trial in military populations, repeated ketamine infusions did not reduce PTSD symptoms more than a placebo.
A 2022 trial tested repeated ketamine infusions for PTSD in veterans and active-duty service members whose PTSD hadn't responded to earlier treatment.
In this randomized, placebo-controlled trial, 158 veterans and active-duty service members with treatment-resistant PTSD received eight ketamine infusions over about four weeks, or a placebo, without knowing which. On the main PTSD measures, the ketamine groups did no better than placebo. The higher ketamine dose did rapidly ease depression more than placebo — but that was a secondary finding, not what the trial was built to test. It's an important negative result: for PTSD specifically, this trial did not support ketamine infusions on their own.
This double-blind, randomized, placebo-controlled multicenter trial (n=158) tested repeated intravenous ketamine (0.2 or 0.5 mg/kg, eight infusions twice weekly) against placebo in veterans and active-duty service members with treatment-resistant PTSD. There were no significant group-by-time interactions for PTSD symptoms on the PCL-5 or CAPS-5. As a secondary finding, the standard 0.5 mg/kg dose improved depression (MADRS) significantly more than placebo.
The trial was well-powered and rigorously designed (randomized, double-blind, placebo-controlled), which makes the negative PTSD result informative rather than merely inconclusive. The depression benefit was a secondary outcome and should be read cautiously. Participants had treatment-resistant PTSD, and ketamine was given as infusions alone, not paired with trauma-focused psychotherapy.
The negative PTSD result contrasts with ketamine's established rapid antidepressant effects and with smaller studies pairing ketamine with prolonged exposure therapy, which reported preliminary feasibility and benefit (Shiroma et al., 2020). A later meta-analysis pooling military ketamine studies reported overall symptom improvement across pain, depression, and PTSD combined (Liu et al., 2024) — but that pooled, mixed-outcome estimate is not PTSD-specific, and this trial remains a rigorous single test of ketamine infusions for PTSD in the military.
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