Beyond Depression

Depression is where ketamine research began, but a substantial share of the trials published since 2023 have targeted other conditions — particularly post-traumatic stress disorder and obsessive-compulsive disorder. The results are genuinely encouraging in places and genuinely disappointing in others, and the honest summary requires both halves.

PTSD: A Split Randomized Record

The positive trials

The foundational randomized evidence comes from Feder and colleagues (American Journal of Psychiatry, 2021), who randomized 30 patients with chronic PTSD to six ketamine infusions or midazolam. CAPS-5 scores were 11.88 points lower in the ketamine group, a large effect (Cohen d = 1.13), with 67% responding versus 20% on midazolam.

A 2025 trial from New Zealand extended this. Beaglehole, Glue and colleagues (BJPsych Open, October 2025) ran a double-blind crossover study in 33 patients with treatment-resistant PTSD, using fentanyl as an active control to help mask ketamine's subjective effects. Response rates at 24 hours, defined as a greater than 50% reduction on the Impact of Event Scale-Revised:

  • Fentanyl control: 18%
  • Ketamine 0.5 mg/kg: 64%
  • Ketamine 1.0 mg/kg: 81%

The dose-response pattern is notable, but the sample was small, the design was crossover, and follow-up was short.

The negative trial that matters

Abdallah and colleagues (Neuropsychopharmacology, 2022) conducted the largest randomized ketamine PTSD trial to date: 158 veterans and active-duty service members receiving eight infusions. There was no significant group-by-time effect on either the PCL-5 or CAPS-5. Ketamine did produce a rapid antidepressant effect in that population, but it did not outperform control on PTSD symptoms.

Any clinic presenting ketamine as an established PTSD treatment is overstating the record. The most defensible reading is that ketamine shows promise for PTSD, with conflicting results in the two largest randomized efforts and unresolved questions about which patients respond.

Real-world data at scale

Observational data is much larger. McInnes and colleagues (Psychiatry Research, 2025) analyzed 8,136 PTSD patients treated with IV ketamine in real-world clinics, 87% of whom also had depression. By the sixth infusion, model-estimated improvements were 22.4 points on the PCL-5 and 7.1 points on the PHQ-9, with the largest gains concentrated in the first three treatments. Registry data of this kind cannot separate drug effect from expectancy, regression to the mean, or concurrent care — but the size and consistency are hard to dismiss.

Ketamine-Assisted Psychotherapy for PTSD

Because ketamine's acute effects fade, several groups have tested pairing infusions with structured trauma therapy.

  • Feder and colleagues (Journal of Clinical Psychiatry, April 2025) combined ketamine infusions with Written Exposure Therapy in an open-label trial of 14 patients with chronic PTSD. Mean CAPS-5 fell from 41.6 to 20.8 at 12 weeks, with 69% meeting response criteria. No control group, so the effect cannot be attributed to ketamine specifically.
  • A 2026 individual-participant-data meta-analysis (Psychotherapy and Psychosomatics) pooled 12 ketamine-assisted psychotherapy studies and 533 participants. The most consistent predictor of greater improvement was higher baseline symptom severity — a finding that also raises regression-to-the-mean concerns.

Ketamine-assisted psychotherapy is a plausible and actively studied model, but as of now it rests largely on open-label and uncontrolled data.

OCD: Small Trials, Short Effects

OCD research is at an earlier stage. The same New Zealand group published a double-blind crossover trial in the Journal of Psychopharmacology (January 2025) involving 12 randomized patients with treatment-resistant OCD, 10 of whom completed it. Both ketamine doses produced greater Y-BOCS reductions than the fentanyl control at 1, 2, and 24 hours — but the residual difference at 168 hours (one week) was not statistically significant.

Interpretation with 10 completers should be cautious. What the OCD literature currently supports is a transient acute reduction in obsessive-compulsive symptoms in some patients, not a durable treatment. Exposure and response prevention therapy and SSRIs remain the evidence-based standard.

Anxiety Disorders

A systematic review by Masdrakis and colleagues (Journal of Psychopharmacology, December 2025) covered 78 studies of ketamine and esketamine for anxiety disorders and anxiety symptoms in depression. Anxiety symptoms decreased across both populations, and benefits were sustained with repeated or maintenance dosing — but relapse followed discontinuation, and the authors noted that no study primarily investigated a DSM-5 anxiety disorder using esketamine. Most of what we know about ketamine and anxiety is derived from depression trials in which anxiety was a secondary measure.

What to Take From This

  • PTSD: Promising but unsettled. Two contradictory large randomized trials; large supportive observational datasets.
  • OCD: Early. Small crossover trials show short-lived acute benefit only.
  • Anxiety: Mostly secondary-outcome evidence; effects appear to require ongoing dosing.
  • Across all three: First-line trauma-focused and cognitive behavioral therapies remain the standard of care, and ketamine is best framed as an adjunct being studied, not a replacement.

Our overview of ketamine for PTSD covers proposed mechanisms in more depth. If you are considering treatment, search clinics by state and ask specifically whether trauma-focused therapy is integrated into their protocol.

Sources

  • Beaglehole B, Glue P, et al. Ketamine for treatment-resistant post-traumatic stress disorder: double-blind active-controlled randomised crossover study. BJPsych Open. 2025;11(6). doi:10.1192/bjo.2025.10854
  • Beaglehole B, Glue P, et al. Ketamine for treatment-resistant obsessive-compulsive disorder: Double-blind active-controlled crossover study. J Psychopharmacol. 2025;39(1):23-28. PubMed 39609659
  • Feder A, et al. Combining Ketamine Infusions and Written Exposure Therapy for Chronic PTSD: An Open-Label Trial. J Clin Psychiatry. 2025. PubMed 40215385
  • McInnes LA, et al. A retrospective analysis of ketamine intravenous therapy for post-traumatic stress disorder in real-world care settings. Psychiatry Research. 2025. PubMed 40848332
  • Abdallah CG, et al. Repeated ketamine infusions for PTSD: a randomized controlled trial. Neuropsychopharmacology. 2022. PubMed
  • Masdrakis VG, et al. Ketamine/esketamine pharmacotherapy for treatment of anxiety disorders and anxiety symptoms in depression: Systematic review. J Psychopharmacol. 2025. doi:10.1177/02698811251389583