Efficacy of hyperbaric oxygen therapy in the treatment of depression

Table 1 Search phrases and terms utilised across the assessed databases

Database	Search string
PubMed	[("Hyperbaric Oxygenation"(MeSH Terms) OR "hyperbaric oxygen therapy"(All Fields) OR HBOT (All Fields)] AND ["Depressive Disorder"(MeSH Terms) OR "depression"(All Fields)]
EMBASE	('Hyperbaric oxygen therapy'/exp OR HBOT) AND ('depression'/exp OR 'depressive disorder'/exp)
PsycINFO	(DE "Hyperbaric Treatment" OR "hyperbaric oxygen therapy" OR HBOT) AND (DE "Depression" OR DE "Major Depressive Disorder")
Cochrane Library	(Hyperbaric NEAR/5 oxygen NEAR/5 therapy OR HBOT) AND (depression OR depressive disorder)
Scopus	((TITLE-ABS-KEY ("hyperbaric oxygen therapy") OR TITLE-ABS-KEY (HBOT)) AND (TITLE-ABS-KEY (depression OR depressive disorder)))
Web of Science	("Hyperbaric oxygen therapy" OR HBOT) AND (depression OR "depressive disorder") AND Language: (English)

Table 2 Demographic variables assessed across the selected trials

Ref.	Country	Protocol	Sample size (n)	Age range (years)	Male: Female ratio
Feng and Li[23], 2017	China	RCT	60	18-50	42:18
Guo et al[24], 2023	China	RCT	180	22-60	104:86
Harch et al[25], 2020	United States	RCT	62	18-65	28:34
Koźmin-Burzyńska et al[26], 2016	Poland	RCT	50	28-80	41:9
Mi et al[27], 2021	China	RCT	64	18-65	Unspecified
Zilberman-Itskovich et al[28], 2022	Israel	RCT	73	48.4 ± 10.6 (mean)	29:34

RCT: Randomized controlled trials.

Table 3 Effect of hyperbaric oxygen therapy on depression as observed across the included trials

Ref.	Treatment duration	Outcome measures	Baseline scores	Post-treatment scores	Statistical significance	Inference drawn
Feng and Li[23]	8 weeks	HAM-D, HAMA, ASIA, FIM	No significant difference in HAM-D, HAM-A, ASIA, FIM scores (P > 0.05)	Significant reduction in HAM-D and HAM-A scores in HBOT group compared to control (P < 0.05); significant increase in ASIA and FIM scores in HBOT group (P < 0.05)	P < 0.05 for HBOT vs control in HAM-D, HAM-A, ASIA, FIM	HBOT significantly improves both depression and functional outcomes in SCI patients
Guo et al[24]	8 weeks	MADRS, NIHSS	No significant difference in MADRS, NIHSS scores (P > 0.05)	Greater reduction in MADRS scores in HBOT group (14.3 ± 5.2) vs control (18.1 ± 3.5), P < 0.001; greater improvement in NIHSS scores in HBOT group (12.2 ± 4.0) vs control (16.1 ± 3.4), P < 0.001	P < 0.001 for HBOT vs control in MADRS, NIHSS	HBOT effectively reduces depression severity and improves neurological function
Harch et al[25]	8 weeks	NSI, cognitive tests (Memory Index, ANAM 4), HAM-D, HAM-A, PSQI, QOLIBRI, PCL	No significant difference in baseline scores reported	Significant 26.3-point decrease in NSI scores in HBOT group vs 2.5-point decrease in control (P < 0.0001); Improved Memory Index, ANAM 4, HAM-D, HAM-A, PSQI, QOLIBRI, PCL in HBOT group	P < 0.0001 for NSI; significant improvements in other measures	HBOT provides substantial relief from post-concussion symptoms and enhances cognitive and emotional well-being
Koźmin-Burzyńska et al[26]	6 weeks	HbA1c, PHQ-9, BHS, HADS A, HADS D, Hamilton Depression Scale	No significant correlations for duration of diabetes and DFS	Higher HbA1c levels correlated with increased depressive symptoms (HADS D, r = 0.20, P < 0.05)	Significant correlation for HbA1c and depressive symptoms (P < 0.05)	HBOT may reduce depressive symptoms, particularly in patients with higher HbA1c levels and severe tissue damage
Mi et al[27]	6 weeks	HAM-D, MoCA	Control: 23.56 ± 4.26; observation: 23.98 ± 4.52 (HAM-D); no significant difference (P > 0.05)	Significant reduction in HAM-D scores at 2 weeks in observation group vs control (P < 0.05); no significant difference at 4 weeks and 6 weeks (P > 0.05)	Significant difference at 2 weeks (P < 0.05)	HBOT combined with escitalopram showed rapid improvement in depression scores at 2 weeks; significant improvement in cognitive function at 4 weeks and 6 weeks
Zilberman-Itskovich et al[28]	8 weeks	Cognitive function, SF-36, PSQI, BSI-18, brain imaging	No significant differences in baseline scores reported	Significant improvement in cognitive function (d = 0.495, P = 0.038); improvements in SF-36, PSQI, and BSI-18 scores; increased gray-matter cerebral blood flow	Significant improvements in multiple measures (P < 0.05)	HBOT significantly improved cognitive function, depressive symptoms, sleep quality, and brain perfusion

HbA1c: Glycated hemoglobin; PHQ-9: Patient Health Questionnaire-9; BHS: Beck Hopelessness Scale; HADS A: Hospital Anxiety and Depression Scale-Anxiety subscale; HADS D: Hospital Anxiety and Depression Scale-Depression subscale; HAM-D: Hamilton Depression Rating Scale; HAM-A: Hamilton Anxiety Rating Scale; ASIA: American Spinal Injury Association; FIM: Functional independence measure; SF-36: Short Form-36 Health Survey; PSQI: Pittsburgh Sleep Quality Index; BSI-18: Brief Symptom Inventory-18; MoCA: Montreal Cognitive Assessment; ANAM 4: Automated Neuropsychological Assessment Metrics, Version 4; QOLIBRI: Quality of Life after Brain Injury; PCL: Post Traumatic Stress Disorder Checklist; HBOT: Hyperbaric oxygen therapy; SCI: Spinal cord injury; NSI: Neurobehavioral Symptom Inventory; DFS: Disability Functional Scale.

Table 4 Vote-count summary of hyperbaric oxygen therapy efficacy across outcome domains (n = 6 randomized controlled trials)

Domain	Significant benefit (HBOT > control)	No significant difference	Significant harm
Mood/depression scales	5	1	0
Cognition/neuropsychology tests	3	11	0
Functional/QoL indices	4	0	0
Perfusion/imaging metrics	1	0	0

¹Two trials did not administer cognitive tests, so denominator = 4.

“Significant benefit”: At least one primary outcome in that domain showed P < 0.05 favouring hyperbaric oxygen therapy (studies could contribute to more than one domain). Numbers add up to > 6 because individual papers reported multiple endpoints. HBOT: Hyperbaric oxygen therapy.

Table 5 GRADE assessment of the selected trials

Study design	Number of studies	Common finding	Bias risk	Variability	Indirect evidence	Precision	Other factors	Certainty
RCT	6	HBOT improves depression, cognitive function, and functional outcomes	Low to moderate	Low	Low	Moderate	None	Moderate

RCT: Randomized controlled trials; HBOT: Hyperbaric oxygen therapy.