HBO Therapy for Post-Traumatic Stress Disorder

CBS news recently highlighted encouraging HBO efficacy data in patients diagnosed with combat-related PTSD, most of whom were refractory to standard care. (1) Its authors are to be congratulated for this undertaking. Any therapeutic intervention that improves the well-being of active and retired military personnel suffering this debilitating condition is heartening and this study appears a step in that direction. As the report has created considerable interest we have been asked to provide some related commentary, particularly given that caveats exist.

As discussed in the program, PTSD involves significant disability/morbidity and is frequently associated with combat-related traumatic brain injury. Some have referred to PTSD/TBI as the signature injurious complex of the middle east war on terror, with an estimated US prevalence of 5-6%. Conventional treatment focuses on psychotherapy and pharmacotherapy, which includes agents that treat symptoms of depression and anxiety, along with stress-relieving interventions. As many such treated patients don’t achieve remission and attendant suicidal ideology omnipresent, a Department of Veterans Affairs 2018 “Evidence Brief” acknowledged the need for innovative therapies. Specifically referencing HBO therapy, it noted that large benefits reported in case series have not been replicated in high quality and well-controlled clinical trials. Referenced trials had resulted in either no demonstrable benefit, benefit that was not enduring, or benefit evident in both treatment and sham groups. In 2022 the Department of Defense opined that “At the present time there is no consensus opinion of the medical community to explain the lack of difference between active treatment (HBO therapy) and control (referencing the trial in which both groups benefited), or the observed benefits in case studies, although competing explanations exist”. Both the VA and DoD argue for more research of greater methodological vigor to differentiate placebo effects from biological effects. This would require trial design that includes formal randomization, sham-controls, provider/assessor blinding and long-term follow-up.

The study introduced by CBS was indeed sham-controlled and provider/assessor blinded but lacked sufficient follow-up to determine if reported benefits were enduring, although it was mentioned that longer follow-up data was previously reported in a less rigorously designed trial. The study’s treatment course was a somewhat arbitrary 60 chamber sessions. I say somewhat as this is the standard number employed within the senior author’s commercial enterprise for essentially every promoted condition. This enterprise has argued elsewhere that only their multiplace hyperbaric chambers are suited to rendering PTSD care, and other proposed indications, as they use an “unique/exclusive” dosing protocol. They further argue that such benefits are not expected to be achieved in monoplace chambers. This is in part, they incorrectly state, as “they lack an air break capability” (when in fact one was introduced into monoplace chamber operations as long ago as 1984 for the purpose of CNS oxygen toxicity mitigation) to adhere to their study protocol, although it is chiefly because of the senior author’s long-held bias. The published paper goes as far as to specifically rule out the monoplace chamber,  likewise all hyperbaric facilities lacking institutionally available professionals in the field of PTSD treatment. I tend to think that outside referral of patients to such specialists (some of whom may already be involved in their care) might be a reasonable enough alternative should memory resurfacing occur, or PTSD symptoms worsen.  

What this group considers unique dosing is employment of intermittent air breathing, namely 20/5 minutes oxygen and air cycling, purportedly    “tricking” brain tissue into believing it is indeed hypoxic during air breathing while oxygen levels aren’t at the point of conventionally defined hypoxia. This “hyperoxia-hypoxic paradox” (there also exists a “normobaric oxygen paradox”)  has been studied in numerous medical and surgical settings over the past two decades and considered to represent a powerful trigger for the regenerative process. This would include stem cell mobilization and resultant angiogenesis/neurogenesis in the context of PTSD/TBI patients. I struggle a bit with acceptance of 20/5 cycling and am presently unconvinced of its therapeutic necessity. Previous research has demonstrated that hyperbaric oxygenation induces these regenerative processes in the lab and clinical settings in its absence (thoughtfully summarized by Barata et al. 2024). One randomized controlled crossover trial published after the VA/DoD reviews referenced above did identify a statistically significant improvement in PTSD symptoms lasting at least two months in patients who underwent 40 sessions at ~1.5 ATA oxygen for 60 minutes without intermittent air breaks. (Harch et al. 2020) This RCT was unblinded and lacked sham controls so inherently susceptible to bias in the context of evidence-based medicine.

Angiogenesis is one of hyperbaric medicine’s principal mechanisms and commonly employed for late radiation tissue injury and diabetic foot ulcers. It is effectively generated without air breaks at 2.0 ATA and with air breaks (30/5 or 30/10) for CNS oxygen toxicity mitigation at higher pressures. These dosing protocols were effectively mobilizing stem cells and inducing angiogenesis decades prior to the Israeli group’s approach.

My personal view is that this trial result must be independently verified, preferably by those without potential commercial bias. It is also my view that this group in question has been a little too quick to monetize their research data prior to its independent verification. Their claim that HBO induces telomere lengthening is a case in point, a finding that was criticized for its unconventional statistical methodology, considered sufficient to invalidate its conclusions. (Mitteldorf J, 2020) Yet this single 26-patient study formed the basis for promoting (at US$60,000.00 per 60 sessions) their private hyperbaric facilities “to reverse the biology of aging”, “maximize cognition”, “optimize golf performance” and several other largely speculative disorders. In a recent LinkedIn post (11/17/2024) the senior author proclaimed, “Our latest study at AVIV Clinics is setting new standards in PTSD research among veterans”. As his AVIV private practice clinics are in Central Florida and Dubai and the published paper cites Shanir Medical Center, Israel as the research location, and where CBS filmed the researchers, his statement again seems a little commercially self-serving.   

Regarding selection of their 60-session threshold, this does not appear based upon studied comparative dosing data. Would 50 sessions suffice? What about the 40 employed by Harch, et al? Not the least one should be sensitive to patients who are likely to pay for this hefty price tag out of pocket. Hyperbaric practitioners readily appreciate HBO promotes healing of injured tissue elsewhere and is only provided to stimulate a healing response  to the point injured tissue becomes self-sustaining in its healing trajectory. Among other things it helps to avoid unnecessary costs.

There is also a political perspective to all of this, with intense lobbying by mostly well-intentioned advocates. This puts congressmen and others in a potentially difficult position. They uniformly want nothing but the most effective care for active-duty personnel and those retired. But they often lack sufficient medical knowledge, or ready access to it, to determine the validity of proposed innovative therapies to make sound decisions and recommendations and likewise use health care resources responsibly. This is particularly the case for studies involving conflicting HBO trial results.

It is my hope that additional hyperbaric research will soon be underwritten by the DoD, or the Veterans Administration, as suggested by the North Carolina congressman interviewed in the program. These two bodies seem the most logical to undertake this and certainly have the requisite resources. Given the high percentage of patients failing to benefit from standard care there is great  urgency to identify effective adjuncts. At least one more positive hyperbaric trial, at the yet to be conducted Phase III RCT level (defined as generating evidence that may lead to a change in healthcare policy and standard of care) would go a long way to formalizing acceptance and facilitating clinical access.

Until then, my view is that HBO therapy remains investigational for PTSD. This does not preclude its use but requires a carefully worded informed consent (including a balanced view of expectations), some thought regarding a dosing protocol and not the least consideration as to who is expected to pay. Finally, as its use would represent an off-label indication, the FDA does not permit overt marketing of one’s availability to treat PTSD.

1.      Doenyas-Barak K, et al. Hyperbaric Oxygen Therapy for Veterans with Combat-Associated Posttraumatic Stress Disorder: A Randomized, Sham Controlled Clinical Trial. Journal Clinical Psychiatry 2024;85(4):