Abstract
OBJECTIVE: Emerging evidence suggests that hyperbaric oxygen therapy (HBOT) promotes neuroplasticity and alleviates symptoms in individuals with post-traumatic stress disorder (PTSD). As a biologically based treatment, HBOT may demonstrate a threshold effect, wherein sufficient treatment leads to sustained symptom improvement, while insufficient treatment results in diminishing benefits. This study tested the threshold hypothesis reanalyzing the end of treatment and a 3-month follow-up symptoms scores of a randomized controlled trial (RCT) comparing HBOT to sham treatment in 56 male veterans with treatment-resistant PTSD. METHODS: A post hoc analysis was conducted on data from the RCT. The elbow method identifies thresholds in the relationship between end-of-treatment improvement and follow-up outcomes. Spearman's rank correlation was used to assess the relationship between changes in cluster-specific symptoms and total CAPS scores at the end of treatment and at follow-up evaluation. RESULTS: Participants achieving ≥ 35% improvement by the end of treatment demonstrated continued improvement at follow-up (p = 2e(-6)). Significant correlations were observed between changes in each of the symptom clusters and total CAPS scores, with the strongest correlation in intrusive symptoms (Cluster B, r = 0.74, p = 10e(-4) and r = 0.80, p = 10e(-4)). Changes in avoidance (Cluster C, r = 0.70, p = 10e(-4)) at the end of treatment were the best predictors of follow-up improvements. CONCLUSIONS: A threshold effect is evident in HBOT treatment for PTSD, where ≥ 35% improvement posttreatment predicts continued gains. Symptom reduction beyond the threshold may serve as a target for HBOT when prescribed for PTSD. The suggested underlying physiological mechanisms, involving bistable circuit dynamics, justify evaluating potential threshold effect in other treatment modalities. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT04518007.