Efficacy of hyperbaric oxygen therapy in the treatment of depression

Abstract

BACKGROUND

Hyperbaric oxygen therapy (HBOT) has been explored as a potential treatment for depression, with various studies indicating its benefits on psychological, cognitive, and functional outcomes.

AIM

To evaluate the efficacy of HBOT in treating depression.

METHODS

A systematic review of randomized controlled trials was conducted to assess the impact of HBOT on depression. Studies were identified through database searches, screened for eligibility, and assessed for bias. Outcome measures included standardized depression scales, cognitive assessments, and functional evaluations.

RESULTS

It was observed across the 6 included trials that HBOT significantly reduced depressive symptoms and improved functional outcomes across multiple studies. Improvements in psychological and neurological measures were consistently reported. Additionally, substantial relief from post-concussion symptoms and enhancements in cognitive and emotional well-being were noted. Some studies highlighted the correlation between physiological markers, such as hemoglobin A1c levels, and depressive symptoms, suggesting HBOT's broader therapeutic potential. Combining HBOT with pharmacological treatments showed rapid improvements in depression and cognitive function, further supporting HBOT's efficacy.

CONCLUSION

HBOT demonstrated significant efficacy in reducing depressive symptoms and improving cognitive and functional outcomes. The therapy's potential benefits extended across various measures, indicate its potential as a multifaceted treatment for depression. Further research is recommended to explore HBOT's mechanisms and optimize treatment protocols.

Key Words: Hyperbaric oxygen therapy; Depression; Systematic review; Cognitive function; Functional outcomes; Therapeutic efficacy

Core Tip: This systematic review synthesizes evidence from six randomized controlled trials evaluating hyperbaric oxygen therapy (HBOT) as an adjunct or stand-alone treatment for depression, including treatment-resistant and comorbid presentations. Across diverse populations, HBOT consistently reduced depressive symptom scores, improved cognition, functional independence, sleep quality, and cerebral perfusion, and in some studies accelerated response when combined with antidepressants. These findings position HBOT as a biologically plausible, multimodal neuromodulatory strategy for mood disorders that extends beyond symptom relief to neurocognitive recovery and functional restoration.

INTRODUCTION

Depression is a major public health problem characterized by persistent low mood, anhedonia, psychomotor and cognitive disturbance, sleep and appetite changes, and functional impairment. According to the World Health Organization, it is among the leading causes of disability worldwide and is estimated to affect 264 million people. Despite guideline-directed care, a significant portion of patients do not achieve remission; as many as one-third develop treatment-resistant depression (TRD), which is insufficiently responsive to conventional antidepressant pharmacotherapy and psychotherapy. In addition to enduring longer morbidity, this population exhibits increased relapse rates and greater consumption of healthcare services, instigating the necessity for novel biological treatments beyond monoaminergic neuromodulation[1,2].

Hyperbaric oxygen therapy (HBOT) has classically been indicated in decompression sickness, carbon monoxide poisoning, and difficult wound healing but has recently been investigated in neuropsychiatric and neurocognitive settings[3]. HBOT consists of breathing 100% oxygen in a pressurized chamber, which substantially increases dissolved oxygen in plasma, raises tissue oxygen tension, and enhances perfusion to hypoxic or metabolically stressed regions[4]. The rationale for testing HBOT in depression is biologically multifactorial. Experimental and early clinical data suggest that HBOT can: (1) Downregulate pro-inflammatory cytokines and shift immune signalling toward an anti-inflammatory profile-relevant, because chronic low-grade inflammation is repeatedly implicated in depressive pathophysiology; (2) Promote neuroplasticity, including synaptic remodelling and circuit-level recovery in regions governing mood and cognition; and (3) Stimulate angiogenesis and microvascular repair, potentially improving cerebral blood flow in areas that often demonstrate hypoperfusion in patients with depressive symptoms[5-11]. Recent studies provide direct support for the three pillars of HBOT action discussed above. In a 2024 Frontiers review, repeated HBOT sessions were shown to up-regulate growth-associated protein-43 and synaptophysin, enhancing the recovery of motor functions after suction ablation of the right sensorimotor cortex[12]. Another study investigated neuronal cells migration in transient brain ischemic rats after HBOT and found that HBOT increased brain-derived neurotrophic factor expression and promoted cell migration toward the penumbra area[13]. Parallel to this, HBOT has been reported to mitigate oxidative stress and support antioxidant defences. This is noteworthy, since oxidative injury to neuronal lipids, proteins, and DNA has been associated both with symptom severity and with cognitive slowing in depressive illness[14]. These mechanisms suggest that HBOT may act not only on mood but on larger neurobiological recovery domains such as attention, processing speed, fatigue, sleep quality, and functional independence. For this reason, HBOT has been trialled not only in primary depressive presentations but also in those patients with secondary symptoms of depression related to neurological or systemic conditions-such as post-stroke syndromes, traumatic brain injury, spinal cord injury, diabetic chronic wounds, and even post-coronavirus disease (COVID) states. In these contexts, mood disturbance commonly co-occurs with cognitive deficits, autonomic dysregulation, pain, and functional loss, which makes HBOT appealing as a systems-level intervention rather than a pure antidepressant agent.

Clinical translation, however, is not straightforward. The available studies to date are heterogeneous in design, population, and outcome definition. Some trials recruit individuals with formally diagnosed depressive disorders, while others assess depressive symptom burden as a secondary outcome in medically complex cohorts. Outcomes range from changes in standardized depression severity scales, to cognitive performance metrics, to objective imaging surrogates of cerebral perfusion, to gains in activities of daily living and independence. The follow-up durations vary, as does the quality of blinding and comparator conditions (e.g., sham vs usual care)[15-19]. Although several reports thus describe clinically meaningful symptom improvement after HBOT, the consistency, durability, and generalizability of these effects remain uncertain. Moreover, safety, tolerability, and feasibility (cost, chamber access, and session frequency) have not been uniformly or systematically characterized in the psychiatric context. Accordingly, this systematic review aims to synthesize the published evidence on HBOT in depressive presentations both in the context of primary major depressive disorder (MDD) and in depression associated with neurological or medical comorbidity. The goals are to describe observed therapeutic effects on mood, cognition, function, cerebral physiology, and fatigue/sleep-related outcomes; summarize reported safety and tolerability signals; and critically appraise whether HBOT should currently be considered a viable clinical adjunct or, rather, an investigational, hypothesis-generating modality that warrants larger, protocol-standardized randomized trials.

MATERIALS AND METHODS

Eligibility criteria

We conducted a systematic review based on the reporting guidelines of PRISMA[20]. The protocol for this systematic review was prospectively registered in the PROSPERO database (Registration No. CRD420251069707). More details can be accessed at https://www.crd.york.ac.uk/PROSPERO/view/CRD420251069707. This reporting will help in rendering the investigation methodology and findings clear and transparent with a high degree of rigour. A structured PECO protocol for Population, Exposure, Comparator, and Outcome is applied as guidance to the research question and for inclusion criteria of the literature search and subsequent analysis. Below is the protocol: (1) Population (P): Studies including adults aged 18 years and older with clinical depression, including MDD, TRD, and dysthymia were included. We also looked for studies that had comorbid conditions such as postconcussion syndrome and diabetes to understand the generalisability of the findings; (2) Exposure (E): The efficacy of HBOT was studied with various protocols including pressure levels for example between 1.5 to 2.5 ATA and the duration exposure in weeks or months. All these variables were incorporated into outcomes; (3) Comparator (C): The comparators were the standard of usual care for depression, being either medication, psychotherapy, or a combination of both. We also included studies with no-treatment control or sham HBOT that controlled for placebo effects; and (4) Outcome (O): The primary outcomes were changes in depression symptoms, evaluated by validated psychiatric rating scales, such as the Hamilton Rating Scale for Depression (HAM-D) and the Montgomery-Åsberg Depression Rating Scale (MADRS). We also considered cognitive assessments, including the Mini-Mental State Examination and the Montreal Cognitive Assessment (MoCA), to clarify how cognitive improvements were measured.

Search strategy

We set up a search protocol that was to integrate searching across six databases, namely PubMed, EMBASE, PsycINFO, Cochrane Library, Scopus, and Web of Science. The strategy was meant to retrieve relevant studies from the terms that were suitable in their keywords and Boolean operators (Table 1). We did not include grey literature in our search, such as conference abstracts and theses because we wanted to minimize publication bias. We only considered publications in the English language only meaning our study will be subjected to language bias as one of our limitations.

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)

Data extraction protocol

Following the literature search, all those studies that met the inclusion criteria were prepared for data extraction. Data extraction was carried out independently by two reviewers. Pre-designed data extraction forms were used in order to avoid inconsistencies and bias. Discussion resolved or sought opinion of third reviewer on disagreements on certain points. We planned the data extraction form to capture critical information from each study: Details of the study, study design, participant characteristics, intervention, comparators, outcomes, and results. We recorded the effect sizes, such as Cohen's d or odds ratios, along with the corresponding P-values to provide an even richer interpretation of the findings.

Bias assessment protocol

We considered for the randomized controlled trials (RCTs), the risk of bias, and we used the Cochrane Risk of Bias Tool 2.0 (RoB 2.0)[21]. For the overall certainty of evidence within studies, we applied the GRADE technique[22], considering publication bias, indirectness, inconsistency, risk of bias, and imprecision. Thereafter, for every result, we provided evidence ratings at a level of strong, moderate, low, or extremely low.

RESULTS

Study selection schematics

The article selection process for this study began with the identification of records from several databases, totalling 264 entries. There were no records identified from registries. Before screening, 41 duplicate records were deleted, leaving 223 records to be examined. During the screening process, 43 records were removed due to full-text unavailability, as they remained inaccessible due to restricted access to particular journals and databases that required certain subscriptions or institutional memberships that were not available to us. Subsequently, 180 reports were requested for retrieval. However, 29 reports were not retrieved. Further assessment led to the deletion of further papers for various reasons: 34 reports did not answer to the PECO criteria, 41 were off-topic, 27 were literature reviews, and 43 were scoping reviews. Ultimately, 151 publications were reviewed for eligibility, out of which 6 clinical trials[23-28] were included in the final review. This has been illustrated in Figure 1 below.

Figure 1 Overview of the study inclusion process.

Assessed bias across different domains

As elucidated through Figure 2, most of the included studies showed a low risk of bias with minimal concerns. Feng and Li[23] and Mi et al[27] had a low risk of bias overall, despite some concerns in D3 and D2, respectively. Guo et al[24] showed some concerns in D1 but was otherwise low risk. Harch et al[25] had low risk across most domains but some concerns in D5, leading to an overall rating of some concerns. Both Koźmin-Burzyńska et al[26] and Zilberman-Itskovich et al[28] consistently demonstrated a low risk of bias across all domains.

Figure 2 Bias assessment using the RoB 2.0 tool.

Baseline variables assessed

The data from Table 2 shows the demographic factors analysed across the included RCTs. The investigations lasted from 2016 to 2023, with research undertaken in China[23,24,27], the United States[25], Poland[26], and Israel[28]. The sample sizes varied greatly, ranging from 50 participants[26] to 180 persons[24]. The age ranges of the participants were similarly wide, with studies involving participants as young as 18 years[23,25,27] and as old as 80 years[26]. The gender distribution throughout these investigations showed a predominance of male participants in most trials. For instance, the male-to-female ratios were 42:18[23], 104:86[24], and 41:9[26]. However, one study did not define the gender ratio[27], and another had a fairly equal distribution with 29 males to 34 females[28]. The age range for one study was described as a mean ± SD (48.4 ± 10.6 years)[28], which is distinct from the other studies that provided specific age ranges.

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.

Outcomes measures analysed

The studies in Table 3 elaborates on the impact of HBOT on depression as found across the included trials[21-26]. The study by Feng and Li[23] completed an 8-week treatment and examined results using measures, including Hamilton Rating Scale for Depression (HAM-D), Hamilton Anxiety Rating Scale (HAMA), American Spinal Injury Association (ASIA) score, and functional independence measure (FIM). Guo et al[24] also carried out an 8-week intervention, concentrating on MADRS and National Institutes of Health Stroke Scale (NIHSS). Harch et al[25] assessed an 8-week treatment utilising a comprehensive set of outcome measures, including Neurobehavioral Symptom Inventory (NSI), different cognitive tests [such as the Memory Index and Automated Neuropsychological Assessment Metrics (ANAM 4)], HAM-D, Hamilton Anxiety Scale (HAM-A), Pittsburgh Sleep Quality Index (PSQI), Quality of Life after Brain Injury (QOLIBRI), and Post-Traumatic Stress Disorder Check List (PCL).

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.

Koźmin-Burzyńska et al[26] adopted a 6-week therapy period and analysed outcomes with measures such as hemoglobin A1c (HbA1c), Patient Health Questionnaire-9, Beck Hopelessness Scale, Hospital Anxiety and Depression Scale-Anxiety, Hospital Anxiety and Depression Scale-Depression (HADS D), and the Hamilton Depression Scale. Mi et al[27] adopted a 6-week treatment length, focusing on HAM-D and MoCA. Zilberman-Itskovich et al[28] conducted an 8-week treatment and measured cognitive performance, Short Form (36) Health Survey (SF-36), PSQI, Brief Symptom Inventory-18 (BSI-18), and brain imaging.

Statistical findings observed

Feng and Li[23] detected no significant differences in HAM-D, HAMA, ASIA, and FIM ratings post-treatment (P > 0.05). However, within the HBOT group, there was a substantial drop in HAM-D and HAMA scores and a significant rise in ASIA and FIM scores (P < 0.05). Guo et al[24] showed no significant differences in MADRS and NIHSS ratings post-treatment (P > 0.05). Despite this, the HBOT group demonstrated a higher reduction in MADRS scores (14.3 ± 5.2) compared to the control group (18.1 ± 3.5), and a greater improvement in NIHSS scores (12.2 ± 4.0) compared to the control group (16.1 ± 3.4), both with P < 0.001.

Harch et al[25] did not report significant variations in baseline scores. However, post-treatment, the HBOT group showed a substantial 26.3-point decline in NSI scores compared to a 2.5-point decrease in the control group (P < 0.0001). Additionally, significant improvements were reported in Memory Index, ANAM 4, HAM-D, HAM-A, PSQI, QOLIBRI, and PCL scores within the HBOT group. Koźmin-Burzyńska et al[26] observed no significant connections between the duration of diabetes and DFS. However, greater HbA1c levels were strongly connected with increased depression symptoms (HADS D, r = 0.20, P < 0.05).

Mi et al[27] reported no significant difference in baseline HAM-D scores between control (23.56 ± 4.26) and observation (23.98 ± 4.52) groups (P > 0.05). However, a substantial drop in HAM-D scores was detected in the observation group at 2 weeks compared to the control group (P < 0.05), while no significant differences were noted at 4 weeks and 6 weeks (P > 0.05). Zilberman-Itskovich et al[28] did not report significant variations in baseline scores. Post-treatment, significant increases were noticed in cognitive performance (d = 0.495, P = 0.038), along with improvements in SF-36, PSQI, and BSI-18 scores, and improved gray-matter cerebral blood flow.

Certainty bias assessment

The risk of bias across the included trials[23-28] was graded as low to moderate, showing generally well-conducted research with some minor problems (Table 4). The consistency of findings was poor, meaning that the results were reliably similar across different investigations. Indirectness was similarly minimal, meaning the evidence directly addressed the research issues. Precision was evaluated as moderate, implying that while the results were consistent, some variability in effect sizes or sample sizes could influence the confidence in the estimations. No other important factors altered the overall assessment. Consequently, the certainty of the evidence was graded as moderate, indicating the efficacy of HBOT but also underlining the need for more study to reinforce these findings and address any lingering doubts. The GRADE assessment of the selected trials has been summarized in Table 5 below.

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.

DISCUSSION

HBOT has also been used in treating various ailments like traumatic brain injury, carbon monoxide poisoning, diabetic foot ulcers, and vascular dementia[3,6,29-32]. Serotonin reuptake may further be blocked, and inflammation of the nerve tissues may be reduced, hence having therapeutic effects for depression[32-34]. With the exception of the study by Feng and Li[23], there is still little research in this field despite the fact that this study shows the promise of HBOT in treating depression.

In terms of the findings observed across the included studies, the slightly noticeable effectiveness of HBOT was indeed observed (Figure 3). Improvements in psychological and functional outcomes were demonstrated similarly by Feng and Li[23], Guo et al[24], and Harch et al[25], while additional benefits in cognitive and physiological areas were indicated by Koźmin-Burzyńska et al[26], Mi et al[27], and Zilberman-Itskovich et al[28], demonstrating the therapeutic potential of HBOT.

Figure 3 Evidence map of overall findings observed.

Feng and Li[23] and Guo et al[24] found similar benefits of HBOT on psychological and neurological parameters, including significant reductions in depression and improvements in functional results. Together with significant improvements of cognition and emotional status, Harch et al[25] also reported substantial relief from symptoms related to post-concussion syndrome. These findings fully agree with the psychological improvements of Feng and Li[23] and Guo et al[24], but they also extend toward a wider range of cognitive and quality-of-life measures.

On the other hand, Koźmin-Burzyńska et al[26] slightly digressed by researching depression symptom correlation with HbA1c and found benefits for patients with diabetic issues. Even though this focused on a different topic, it still supported the psychological benefits of HBOT.

Our review showed that HBOT dramatically improved cognitive and functional outcomes and decreased depressed symptoms in a number of conditions, including post-concussion symptoms and diabetes-related issues. These results are consistent with those of Liang et al[35], who found that HBOT treatment for post-stroke depression patients resulted in significantly lower levels of depression severity and neurological impairments as well as fewer side effects when compared to standard treatments. Similar to our recommendations, Krzystanek et al[36] supported our findings and suggested HBOT as a potential augmentation technique for depression that is resistant to treatment. However, they also noted the preliminary nature of the data and the need for more research.

On the other hand, although HBOT decreased coma severity and death in cases of acute traumatic brain injury, its long-term benefits for functioning were unclear, and it showed no immediate improvements in the symptoms of PTSD or chronic mild TBI[37]. This was partly at odds with our results, which showed significant improvements in post-concussion participants' cognitive and emotional functioning.

HBOT is generally considered physiologically tolerable, but it is by no means risk-free and should not be presented as a type of benign supportive care. Adverse effects reported and theoretically anticipated include middle-ear or sinus barotrauma from pressurization, pulmonary oxygen toxicity with prolonged/high-dose exposure, central nervous system oxygen toxicity manifesting as seizures, transient visual changes, and procedure-related anxiety or claustrophobia related to chamber confinement[27-30]. HBOT also requires repeated, supervised sessions in a pressurized chamber, which introduces practical burdens (access, cost, time commitment) that are directly relevant to real-world psychiatric use and may limit scalability outside specialized centres[31,32].

Importantly, several of the randomized and exploratory clinical studies assessing HBOT for depressive symptoms, post-stroke mood disturbance, traumatic brain injury-associated affective symptoms, or post-COVID neurocognitive complaints either did not systematically collect adverse event data or reported “no serious adverse events” without granular description of minor or procedure-limiting effects[27,29,33]. The absence of detailed safety reporting in these trials should not be interpreted as evidence of absence of risk; rather, it likely reflects under-reporting bias or an evidence gap. Veteran affairs evidence syntheses and psychiatric HBOT reviews have specifically emphasized that, in neuropsychiatric indications, safety endpoints (barotrauma rates, seizure incidence, and panic/claustrophobia-related discontinuation) must be prospectively measured and transparently reported alongside symptom change[31,32,34].

Given the chronic and relapsing nature of depression, any intervention proposed as a repeated or maintenance therapy needs to demonstrate not only symptom benefit but acceptable long-term tolerability. Future trials should therefore incorporate predefined adverse event monitoring (otologic exams, pulmonary assessment, neurotoxicity surveillance), document withdrawal/dropout attributable to HBOT intolerance, and explicitly report patient acceptance of the chamber environment[27-29,31-34]. Without these data, it is premature to position HBOT as ready for routine psychiatric deployment, even if preliminary mood and cognitive signals appear favourable.

Limitations

There were several places where the study's limitations were acknowledged. First off, there were some difficulties in directly comparing data and synthesising results due to the variability in outcome measures and assessment methods among the included research. Furthermore, some research had rather small sample sizes, which limited how broadly the results could be applied. The diverse range of patient demographics, including differences in age, depression severity, and coexisting medical conditions, could have affected the results and hindered the ability to draw consistent conclusions. Moreover, the exclusion of non-English studies was also a source of potential bias, along with the lack of long-term follow-up in most trials (since depression is often chronic and relapse-prone).

Future implications and clinical suggestions

Several recommendations can be drawn from the research' combined findings. First, considering HBOT's ongoing efficacy in enhancing psychological, cognitive, and functional outcomes, it can be suggested as a possible therapeutic alternative for those with depression. Given the significant improvements in cognitive and emotional well-being that have been shown, clinical processes should take into consideration incorporating HBOT for patients with neurological issues and post-concussion symptoms. HBOT may provide additional psychological benefits for patients with diabetes-related issues, particularly in relation to depressive symptoms associated with elevated HbA1c levels. Rapid improvements in depression and cognitive function suggest that combining HBOT with pharmaceutical treatments, such as antidepressants, may improve therapeutic outcomes. More research with larger sample sizes, standardized outcome measures, and long-term follow-up is needed to confirm the effectiveness of HBOT and improve its use in treating depression. Studying the fundamental mechanisms behind the therapeutic advantages of HBOT can also help to improve treatment plans and patient outcomes.

CONCLUSION

As per our findings, HBOT significantly reduced depressive symptoms and improved the cognitive and functional results of depression patients. The treatment has demonstrated benefits in a wide range of psychological and neurological measures. Furthermore, HBOT showed notable benefits in improving emotional health and cognitive function, particularly in individuals with diabetes-related issues and those exhibiting symptoms of post-concussion syndrome. These results provide preliminary evidence of HBOT as a potentially effective multimodal treatment for depression, highlighting the need for more studies to improve its delivery and elucidate its underlying mechanisms.