Multi-center, randomized controlled efficacy and comparative-effectiveness study evaluating ketamine, stellate ganglion blocks, combination treatment, and sham treatments for posttraumatic stress disorder and traumatic brain injury-associated headache: a study protocol

01/10/2026

AI Summary

Multi-centre, double-blind RCT across three US and Ukrainian sites randomising 210 PTSD and/or TBI headache patients into four arms in 2:2:2:1 ratio.
Bivariate co-primary outcomes assess change in Headache Impact Test or PTSD Checklist at four weeks, with responders followed to six months.
A pragmatic comparison of ketamine, stellate ganglion block, combination and placebo to generate real-world efficacy and comparative-effectiveness data potentially informing clinical guidelines.

Pain Manag. 2026 Oct 1:1-11. doi: 10.1080/17581869.2026.2738419. Online ahead of print.

ABSTRACT

BACKGROUND: Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are conditions that share common mechanisms and are highly co-prevalent with each other and chronic pain. This pragmatic study will compare ketamine infusions to stellate ganglion blocks (SGB), their combination, and a placebo-sham-controlled arm.

METHODS: A double-blind study conducted at 3 U.S. and Ukrainian sites will be performed. Two hundred ten patients with PTSD and/or TBI-associated headache will be allocated in a 2:2:2:1 ratio to receive SGB/placebo ketamine, ketamine/sham SGB, ketamine/SGB, and placebo/sham. The bivariate co-primary outcome will evaluate change in Headache Impact Test and PTSD Checklist depending on diagnosis, at 4 weeks. Participants who experience a positive binary outcome will remain in the study through 6 months or until their outcome becomes negative.

DISCUSSION: Because PTSD and TBI have no discrete pathophysiological mechanisms and are co-prevalent with pain and psychopathology, they are associated with poor outcomes, polypharmacy, and high non-adherence rates, indicating a need for minimally invasive treatments that obviate these barriers. Whereas both therapies have evidence underpinning efficacy, results in clinical trials are conflicting. This study will provide real-world evidence in generalizable populations on the efficacy and comparative-effectiveness of ketamine and SGB, alone and in combination, with the possibility of changing clinical guidelines.

CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT06608277.

PMID:42817839 | DOI:10.1080/17581869.2026.2738419

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