Key takeaways
- Published May 2024 in Nature Scientific Reports: a randomised prospective trial comparing HBOT vs. FDA-approved pharmacotherapy (pregabalin + duloxetine) in 48 fibromyalgia patients with childhood sexual abuse history.
- HBOT protocol: 60 sessions at 2.0 ATA, 90 minutes each with air breaks — the Efrati Lab neurological protocol.
- Primary endpoint: Fibromyalgia Impact Questionnaire (FIQ) — HBOT showed a large effect size advantage over medication.
- SPECT imaging demonstrated increased activity in pre-frontal and temporal brain regions, correlating with symptom improvement.
- The trial extends the 2015 Efrati fibromyalgia work by targeting a trauma-defined subpopulation and directly comparing with standard-of-care pharmacology.
The study
Zilberman-Itskovich et al. published a randomised prospective clinical trial in Nature Scientific Reports in May 2024 comparing hyperbaric oxygen therapy against FDA-approved pharmacotherapy for fibromyalgia in patients with a history of childhood sexual abuse. Forty-eight participants were enrolled and randomised to either:
- HBOT arm — 60 sessions of 100% oxygen at 2.0 ATA for 90 minutes, with scheduled 5-minute air breaks (the standard Efrati Lab neurological protocol).
- Medication arm — standard-of-care FDA-approved pharmacotherapy: pregabalin (Lyrica) and duloxetine (Cymbalta).
The primary endpoint was the Fibromyalgia Impact Questionnaire (FIQ) — a validated 10-item instrument covering functional ability, pain, fatigue, sleep, and emotional symptoms. Secondary endpoints included emotional status questionnaires, functional measures, pain thresholds, and conditioned pain modulation testing. SPECT brain imaging was performed to assess regional brain activity.
The result
HBOT produced a statistically significant group-by-time interaction favoring the HBOT arm over medication, with a large effect size on the FIQ. Similar advantages were seen across:
- Emotional symptom measures (depression, anxiety)
- Daily functional measures
- Pain threshold and conditioned pain modulation
Critically, SPECT imaging revealed increased activity in the pre-frontal and temporal brain regions in the HBOT arm — and this neuroimaging change correlated with symptom improvement. The medication arm did not show equivalent brain activity changes.
Why trauma-history fibromyalgia?
Fibromyalgia is a heterogeneous syndrome. A substantial literature indicates that fibromyalgia in patients with early-life trauma — particularly childhood sexual abuse — involves distinct neurobiological patterns, including altered brain activity in pain-processing and emotional-regulation regions. The Efrati Lab hypothesis was that HBOT's known neuroplasticity-promoting effects (HIF-1α stabilisation, angiogenesis, M1→M2 macrophage polarisation) would be particularly beneficial in this subpopulation, where symptoms partially reflect altered brain structure and function.
The result supports this hypothesis. The pre-frontal and temporal brain changes seen on SPECT align with areas known to be dysregulated in trauma-history pain populations.
How this extends prior Efrati work
The 2024 paper is the second major Efrati Lab fibromyalgia trial. The Efrati 2015 PLOS ONE trial studied general fibromyalgia using a prospective crossover design and also found significant symptom reduction and SPECT brain changes at 2.0 ATA. Together, the two trials provide:
- Multiple-cohort replication of HBOT benefit in fibromyalgia
- Evidence of a specific trauma-history subpopulation effect
- Direct comparison with standard-of-care pharmacology (not just placebo)
- Consistent SPECT imaging confirmation of a neurobiological mechanism
Where HBOT fits in fibromyalgia care
Standard fibromyalgia care is pharmacological (pregabalin, duloxetine, milnacipran) plus physical therapy, graded exercise, cognitive behavioural therapy, and sleep management. Medications offer modest symptom improvement with significant side-effect profiles.
HBOT appears to offer:
- Larger effect sizes on functional and pain measures in the trial populations studied
- Measurable brain activity changes that medications typically do not produce
- Durability of effect that extends beyond the treatment course (consistent with structural neuroplasticity)
- A favorable safety profile vs. chronic medication exposure
The trade-offs are substantial: the full-course cost ($6,000–$18,000 cash-pay), the 12-week daily commitment, and the fact that HBOT remains off-label and uncovered by insurance for this indication.
Clinical and research implications
For clinicians treating fibromyalgia — particularly in patients with early trauma history — HBOT at the Efrati-protocol dose is now supported by two prospective trials from the same lab, including a head-to-head comparison with pharmacotherapy. The evidence is single-lab and awaits multi-centre replication, but the trial quality and effect sizes are substantial.
For patients: HBOT remains cash-pay. If pursued, choose a facility delivering the full 40-60 session Efrati protocol at 2.0 ATA in a hard-shell chamber. Set realistic expectations — the trial response was significant but not universal, and 20-40% of patients historically show limited benefit.
For researchers: this trial strengthens the case for a UHMS Oxygen Therapy Committee review of fibromyalgia HBOT. The combined 2015 + 2024 evidence from the Efrati Lab, plus the broader meta-analysis literature on HBOT in chronic pain syndromes, is now substantial enough to warrant formal re-evaluation of its research-stage status.
For the full fibromyalgia evidence overview and related studies, see our fibromyalgia evidence page and the studies database.
Frequently Asked Questions
Why specifically childhood sexual abuse patients?
Fibromyalgia is heterogeneous and the trauma-defined subpopulation is thought to have more neuroplasticity-mediated symptoms. The Efrati Lab hypothesis is that HBOT's brain-regenerative effects would be particularly beneficial where symptoms reflect altered brain function from early trauma.
Does this apply to all fibromyalgia patients?
The 2024 trial specifically enrolled trauma-history patients. The earlier 2015 Efrati trial (also PLOS ONE, same lab) studied general fibromyalgia and also showed symptom benefit at 2.0 ATA. Together they support HBOT across fibromyalgia subpopulations, with stronger evidence in trauma subgroups.
Is HBOT covered by insurance for fibromyalgia?
No. Fibromyalgia is not on the UHMS 15 approved indications and is not covered by CMS/Medicare or most US private insurers. Patients typically pay out-of-pocket for a full 40-60 session course.
How does HBOT compare to pregabalin/duloxetine?
In this trial, HBOT produced a significantly larger effect size on the FIQ and secondary emotional/functional measures than the FDA-approved medications. HBOT also demonstrated SPECT-verified brain activity changes that medications typically do not produce.
