Hyperbaric Oxygen Therapy for PTSD: Threshold Effect for Sustained Symptom Improvement in a Biologically Based Treatment

Dor Danan; Yaniv Grosskopf; Avi Mayo; Shai Efrati; Ilan Kutz; Erez Lang; Uri Alon; Keren Doenyas-Barak

doi:10.1002/brb3.70757

Hyperbaric Oxygen Therapy for PTSD: Threshold Effect for Sustained Symptom Improvement in a Biologically Based Treatment

Dor Danan
, Yaniv Grosskopf
, Avi Mayo
, Shai Efrati
, Ilan Kutz
, Erez Lang
, Uri Alon
, Keren Doenyas-Barak

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e70757
Journal	Brain and Behavior
Volume	15
Issue number	8
DOIs	https://doi.org/10.1002/brb3.70757
State	Published - Aug 2025
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.

ASJC Scopus subject areas

Behavioral Neuroscience

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10.1002/brb3.70757

Cite this

@article{aff0c709a9ac4decb36fb528cd30e6b5,

title = "Hyperbaric Oxygen Therapy for PTSD: Threshold Effect for Sustained Symptom Improvement in a Biologically Based Treatment",

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.",

author = "Dor Danan and Yaniv Grosskopf and Avi Mayo and Shai Efrati and Ilan Kutz and Erez Lang and Uri Alon and Keren Doenyas-Barak",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.",

year = "2025",

month = aug,

doi = "10.1002/brb3.70757",

language = "English",

volume = "15",

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T2 - Threshold Effect for Sustained Symptom Improvement in a Biologically Based Treatment

AU - Danan, Dor

AU - Grosskopf, Yaniv

AU - Mayo, Avi

AU - Efrati, Shai

AU - Kutz, Ilan

AU - Lang, Erez

AU - Alon, Uri

AU - Doenyas-Barak, Keren

PY - 2025/8

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N2 - 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.

AB - 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.

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AN - SCOPUS:105013979588

SN - 2157-9032

VL - 15

JO - Brain and Behavior

JF - Brain and Behavior

IS - 8

M1 - e70757

ER -

Hyperbaric Oxygen Therapy for PTSD: Threshold Effect for Sustained Symptom Improvement in a Biologically Based Treatment

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