TITLE: Hyperbaric Oxygen Therapy for Adults with Mental Illness: A Review of the Clinical Effectiveness

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TITLE: Hyperbaric Oxygen Therapy for Adults with Mental Illness: A Review of the Clinical Effectiveness DATE: 27 August 2014 CONTEXT AND POLICY ISSUES Mental illness, including major depressive episode, bipolar disorder, generalized anxiety disorder, alcohol abuse, and other drug abuse or dependence, affects approximately 1 in 3 Canadians at some point in their lives. 1 Depression is the most common mood disorder, with a lifetime incidence of 11.3%, while the lifetime incidence of generalized anxiety disorder is 8.7%. 1 Hyperbaric oxygen therapy (HBOT) is administered inside a treatment chamber and provides the patient with 100% oxygen at high atmospheric pressures. 2 There have been a number of medical conditions in which treatment with hyperbaric oxygen has been investigated, including, but not limited to, treatment of carbon monoxide poisoning, improved wound healing, and decompression sickness and air embolism due to ascending too quickly in aviation or deep water diving. 3 It has been hypothesized that hyperbaric oxygen therapy may be beneficial in the treatment of certain mental health disorders such as post-traumatic stress disorder occurring in the setting of a traumatic brain injury. In an uncontrolled pre-post study, 4 a group of patients with blast-induced post-concussion syndrome with or without post-traumatic stress disorder demonstrated improvement in a number of physical, psychological, and cognitive measured hen tested within a week of completing 30 days of HBOT. The proposed mechanism of action of hyperbaric oxygen in traumatic brain injury is that increasing oxygenation of blood and tissues to supraphysiological levels results in the improvement of neuronal functioning by the reactivation of metabolic or electrical pathways. Stem cell mobilization to sites of injury, immune modulation and impact on neurotransmitters have also been hypothesized as possible mechanisms. 5 Currently, the value of using hyperbaric oxygen therapy in the treatment of mental illness has not been well-established. The purpose of this report was to review existing studies on the use of hyperbaric oxygen therapy for adults with post-traumatic stress disorder, generalized anxiety disorder, or depression. Disclaimer: The Rapid Response Service is an information service for those involved in planning and providing health care in Canada. Rapid responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. Rapid responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material and may contain material in which a third party owns copyright. This report may be used for the purposes of research or private study only. It may not be copied, posted on a web site, redistributed by email or stored on an electronic system without the prior written permission of CADTH or applicable copyright owner. Links: This report may contain links to other information available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners own terms and conditions.

RESEARCH QUESTIONS 1. What is the clinical effectiveness of hyperbaric oxygen therapy for the treatment of adults with post-traumatic stress disorder? 2. What is the clinical effectiveness of hyperbaric oxygen therapy for the treatment of adults with generalized anxiety disorder? 3. What is the clinical effectiveness of hyperbaric oxygen therapy for the treatment of adults with depression? KEY FINDINGS No relevant literature regarding the clinical effectiveness of hyperbaric oxygen for the treatment of adults with post-traumatic stress disorder, generalized anxiety disorder, or depression was identified. METHODS Literature Search Strategy A limited literature search was conducted on key resources including PubMed, Ovid PsycINFO, The Cochrane Library (2014, Issue 7), University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused Internet search. No filters were applied to limit the retrieval by study type. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 1, 2004 and July 29, 2014. Selection Criteria and Methods One reviewer screened the titles and abstracts of the retrieved publications and evaluated the full-text publications for the final article selection, according to the selection criteria outlined in Table 1. Population Intervention Comparator Outcomes Study Designs Table 1: Selection Criteria Adults with post-traumatic stress disorder, generalized anxiety disorder or depression Hyperbaric oxygen therapy Any active treatment (e.g. usual care, pharmacotherapy, counselling) Clinical effectiveness (e.g. symptom reduction), quality of life, safety Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-randomized studies Hyperbaric Oxygen for Mental Illness 2

Exclusion Criteria Articles were excluded if they did not meet the selection criteria outlined in Table 1, if they were duplicate publications of the same study or were published prior to 2004. SUMMARY OF EVIDENCE Quantity of Research Available The literature search yielded 267 citations. No additional studies were identified by searching the grey literature. After screening titles and abstracts, seven potentially relevant studies were selected for full-text review. Of the seven potentially relevant reports, none of them met the selection criteria. Five of the seven reports that were excluded from this review examined participants that were not relevant to the population defined in the selection criteria. Of the other two reports excluded, one did not include a comparator group and the other included a comparative medication that is not currently available in Canada. Appendix 1 describes the PRISMA flowchart of the process for study selection. Summary of Findings There was no evidence found on the clinical effectiveness of hyperbaric oxygen therapy for the treatment of adults with post-traumatic stress disorder, generalized anxiety disorder, or depression. Therefore no summary can be provided. CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING No relevant literature was identified; therefore, no conclusions can be drawn about the clinical effectiveness of hyperbaric oxygen therapy for the treatment of adults with post-traumatic stress disorder, generalized anxiety disorder, or depression. PREPARED BY: Canadian Agency for Drugs and Technologies in Health Tel: 1-866-898-8439 www.cadth.ca Hyperbaric Oxygen for Mental Illness 3

REFERENCES 1. Pearson C, Janz T, Ali J. Mental and substance use disorders in Canada [Internet]. Ottawa (ON): Statistics Canada; 2013 Sep. [cited 2014 Aug 13]. Available from: http://www.statcan.gc.ca/pub/82-624-x/2013001/article/11855-eng.pdf 2. Verghese G, Verma R, Bhutani S. Hyperbaric oxygen therapy in the battlefield. Med J Armed Forces India [Internet]. 2013 Jan [cited 2014 Jul 31];69(1):94-6. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/pmc3862713 3. Mechem CC, Manaker S. Hyperbaric oxygen therapy. 2013 Oct 16 [cited 2014 Aug 26]. In: UpToDate [Internet]. Version 14.0. Waltham (MA): UpToDate; 1992 -. Available from: www.uptodate.com Subscription required. 4. Harch PG, Andrews SR, Fogarty EF, Amen D, Pezzullo JC, Lucarini J, et al. A phase I study of low-pressure hyperbaric oxygen therapy for blast-induced post-concussion syndrome and post-traumatic stress disorder. J Neurotrauma. 2012 Jan 1;29(1):168-85. 5. Wolf G, Cifu D, Baugh L, Carne W, Profenna L. The effect of hyperbaric oxygen on symptoms after mild traumatic brain injury. J Neurotrauma. 2012 Nov 20;29(17):2606-12. Hyperbaric Oxygen for Mental Illness 4

APPENDIX 1: Selection of Included Studies 267 citations identified from electronic literature search and screened 260 citations excluded 7 potentially relevant articles retrieved for scrutiny (full text, if available) 0 potentially relevant reports retrieved from other sources (grey literature, hand search) 7 potentially relevant reports 7 reports excluded: -irrelevant population (5) -irrelevant comparator (2) 0 reports included in review Hyperbaric Oxygen for Mental Illness 5