Hyperbaric Oxygen Therapy for Veterans With Combat-Associated Posttraumatic Stress Disorder: A Randomized, Sham-Controlled Clinical Trial

Objective: Cumulative data indicate that new protocols of hyperbaric oxygen therapy (HBOT) may induce neuroplasticity and improve clinical symptoms of patients suffering from posttraumatic stress disorder (PTSD). The aim of the current study was to evaluate the effects of HBOT on veterans with combat-associated PTSD (CA-PTSD) in a randomized, sham-controlled trial. Methods: Male veterans aged 25-60 years with CA-PTSD, with a Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) score above 20, were included. Exclusion criteria included a history of traumatic brain injury, other psychiatric diseases, or contraindication to HBOT. Participants were randomly assigned to HBOT or sham intervention. Both interventions involved 60 daily sessions, with 90 minutes of either 100% oxygen at 2 atmospheres absolute (ATA) (HBOT) or 21% oxygen at 1.02 ATA (sham) with 5-minute air breaks every 20 minutes. CAPS-5 score, Beck Depression Inventory-II (BDI-II), the Depression, Anxiety and Stress Scale 21 Items (DASS-21), and resting-state functional magnetic resonance imaging (rsfMRI) were assessed at baseline and posttreatment, with the primary end point defined as a 30% reduction in CAPS-5 score from baseline. Results: The study was conducted between February 2020 and July 2023. Of 63 veterans who underwent randomization, 56 completed the study protocol (28 in each group). The HBOT group showed a significant decrease in mean CAPS-5 total score, from 42.57 ± 9.29 at baseline to 25.8 ± 9.5 following HBOT (P < .001) and 25.08 ± 13.08 at follow-up (P < .001). The sham group demonstrated a significant increase in CAPS-5 total score from baseline to follow-up, from 45.11 ± 8.99 to 47.75 ± 11.27 following HBOT (P = .069) and 49.22 ± 10.26 at follow-up (P = .011). Significant improvements in the depression domain of the DASS-21 questionnaire and BDI-II were demonstrated (F = 4.55, P= .03 and F= 4.2, P= .04, respectively). The stress and anxiety domains of DASS-21 did not reach statistically significant levels. Analysis of rsfMRI demonstrated improved connectivity within the 3 main networks (default-mode network, central-executive network, salience network) in HBOT vs sham groups. Conclusions: Dedicated HBOT protocol can improve PTSD symptoms of veterans with CA-PTSD. The clinical improvement was accompanied by enhanced functional connectivity demonstrated by rsMRI.