Effectiveness of Mindful Breathing Exercises on Symptom Reduction, quality of life, and Psychological Well-being in Individuals with Major Depressive Disorder: A Systematic Review and Meta-analysis Protocol

Effectiveness of Mindful Breathing Exercises on Symptom Reduction, quality of life, and Psychological Well-being in Individuals with Major Depressive Disorder: A Systematic Review and Meta-analysis Protocol | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effectiveness of Mindful Breathing Exercises on Symptom Reduction, quality of life, and Psychological Well-being in Individuals with Major Depressive Disorder: A Systematic Review and Meta-analysis Protocol Saad Bin Muaythir, Nombeko Mshunqane, Bashir Bello, Enos Ramano, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7820951/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Introduction Major depressive disorder (MDD) is a prevalent mental health condition marked by persistent sadness, loss of interest, and impaired cognition, significantly affecting quality of life. While pharmacotherapy and psychotherapy are standard treatments, non-pharmacological interventions like mindful breathing exercises have gained attention for their potential to reduce depressive symptoms and enhance well-being. Despite some evidence of effectiveness, a comprehensive, up-to-date synthesis focusing solely on mindful breathing in MDD is lacking. This systematic review protocol will evaluate the impact of mindful breathing exercises on depressive symptom severity, quality of life, and psychological well-being in adults with MDD. Methods and analysis This review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2015 checklists. A comprehensive search of Cochrane, Medline, PEDro, CINAHL, Scopus, Web of Science, and BioMed Central will be carried out from inception to April 2025. Using the PICOs framework, we will include quantitative studies (randomised controlled trials and controlled observational designs) involving adults aged 18 and above who have been diagnosed with MDD using standardised criteria (e.g., DSM-5, ICD-10). Three reviewers will independently screen titles, abstracts, and full texts and extract data using the COVIDENCE software. The risk of Bias Assessment will be conducted using Cochrane RoB 2 (RCTs) and ROBINS-I (non-randomised studies), and the evidence quality will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. A meta-analysis using RevMan 5.4 will pool mean differences, standardised mean differences, or odds ratios if data permit; otherwise, a narrative synthesis will be conducted. The search began in September 2025, with completion anticipated by December 2025. Ethics and dissemination No ethical approval is required as this review uses existing published data. Findings will be disseminated through a peer-reviewed journal and presented at academic conferences. PROSPERO registration : CRD420251032845 Mindful breathing exercises major depressive disorders quality of life psychological well-being Strengths and Limitations of This Study This protocol follows PRISMA-P guidelines and Cochrane methodology, which ensures a rigorous, transparent and reproducible systematic review process. Mindful breathing exercises are inexpensive, simple to use, and widely available. Particularly in environments with limited resources, assessing the efficacy of these approaches provides valuable information for mental health treatment. The review will provide a more comprehensive understanding of patient-centred outcomes by evaluating quality of life and well-being in addition to the reduction of symptoms associated with MDD. The exclusion of non-English studies may introduce language bias, potentially missing relevant evidence from diverse settings. This could create a limitation of the study. Heterogeneity may be introduced by differences in the kind, length, frequency, and mode of delivery of mindful breathing interventions among studies, making direct comparisons and meta-analytical pooling more difficult. Studies with positive results are more likely to be published than those with null or negative results, which could skew the review's findings. Introduction Psychiatric disorders impose a significant global health burden, with major depressive disorder (MDD) standing out as a primary contributor to disability. The Global Burden of Disease study identifies depression as one of the top ten causes of years lost to disability (YLD) in high-income countries, a reflection of its widespread prevalence and debilitating effects 1 . MDD is characterised by persistent low mood, anhedonia (loss of interest or pleasure), fatigue, excessive guilt, low self-esteem, disrupted sleep or appetite, and impaired cognitive function, as delineated in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) 2 3 . These symptoms distinguish MDD from other psychiatric conditions like schizophrenia or bipolar disorder. Yet, its global prevalence, estimated at 13.3% among adults and over 10% in children, marks it as a uniquely pervasive challenge 4 5 . The World Health Organisation (WHO) projects that by 2030, MDD will surpass all other conditions to become the leading cause of disability worldwide, highlighting the critical need for effective, scalable interventions 6 . Beyond its symptomatic toll, MDD profoundly impacts health-related quality of life (HRQoL). Research consistently shows that individuals with MDD experience reduced physical, social, and emotional functioning, often exacerbated by comorbidities such as anxiety, substance use disorders, or chronic physical illnesses like diabetes 7 8 . This multidimensional burden contributes to substantial disability-adjusted life years (DALYs) and premature mortality, which is straining healthcare systems globally 9 . In high-income settings, where mental health resources are relatively accessible, the persistence of MDD-related disability suggests gaps in current treatment approaches 10 . In low- and middle-income countries, these gaps widen due to limited infrastructure, amplifying the public health crisis 10 . Consequently, addressing MDD requires innovative strategies that complement existing therapies and bridge accessibility barriers. Standard MDD management relies on pharmacotherapy (e.g., selective serotonin reuptake inhibitors [SSRIs]) and psychotherapy (e.g., cognitive-behavioral therapy [CBT], interpersonal therapy [IPT]), which are supported by robust evidence 11 . Meta-analyses, such as that by Cuijpers et al. (2008), report moderate to large effect sizes for these interventions in reducing depressive symptoms; however, their limitations are well recognised 12 . Up to 50% of patients exhibit partial or no response to antidepressants, with side effects like weight gain or emotional numbing deterring adherence 13 . Psychotherapy, while effective, demands trained providers and sustained patient engagement, often impractical in resource-scarce settings or for those facing logistical or stigma-related barriers, like in Saudi Arabia 14 15 . These challenges have fueled interest in non-pharmacological alternatives, particularly mindfulness-based interventions, which capitalise on the interplay between emotional regulation, lifestyle, and resilience 16 . Mindful breathing exercises, a focused subset of mindfulness practices, involve structured techniques, such as diaphragmatic breathing, deep breathing, or breath counting, to enhance present-moment awareness and regulate emotional responses 17 . By activating the parasympathetic nervous system, these exercises reduce sympathetic arousal, countering the physiological stress response that is central to MDD’s pathology 18 . Unlike comprehensive mindfulness programs, which blend meditation, body awareness, and cognitive strategies, mindful breathing offers a standalone, accessible practice requires minimal training 19 . Preliminary studies suggest that it may reduce depressive symptoms, improve HRQoL, and enhance psychological well-being, potentially through mechanisms such as increased vagal tone or modulated amygdala-prefrontal cortex connectivity 20 – 22 . However, the evidence is inconsistent, with many trials embedding breathing within broader interventions or lacking rigorous controls 23 24 . Existing systematic reviews have explored mindfulness-based therapies for depression, but rarely isolate mindful breathing’s specific effects 25 26 . A comprehensive meta-analysis that included a range of mindfulness practices was performed, which consequently restricted its relevance to interventions centred solely on breathing 25 . Additionally, a review of exercise therapies was conducted that completely overlooked this particular technique 26 . Given the heterogeneity of MDD and the potential of mindful breathing as a low-cost, scalable adjunct, a targeted systematic review with meta-analysis is warranted. This protocol aims to synthesise evidence on the effects of mindful breathing exercises on depressive symptom severity, quality of life, and psychological well-being in adults with MDD, using meta-analytic techniques to quantify intervention efficacy and guide clinical practice. Methods and analysis Study design Quantitative RCTs and controlled observational studies in English, with no publication year restriction. This systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, ensuring transparency and reproducibility 27 . It will adopt Cochrane methodology for systematic reviews of interventions, incorporating a meta-analysis to provide a quantitative synthesis where feasible 28 . The review is registered on PROSPERO (CRD420251032845) to enhance accountability and minimise duplication. It will include quantitative studies, such as experimental studies, to evaluate the impact of mindful breathing exercises on MDD outcomes. This protocol began the literature search from September 2025, with data extraction anticipated to be completed by December 2025. Search strategy A comprehensive search, conducted in collaboration with an information specialist, will target the Cochrane Library, Medline (via PubMed), PEDro, CINAHL, Scopus, Web of Science, and BioMed Central, spanning from inception to September 2025. Search terms will combine Medical Subject Headings (MeSH) and free-text: (“Major Depressive Disorder” OR “Depression”) AND (“Mindful Breathing” OR “Breathing Exercises”) AND (“Quality of Life” OR “Depressive Symptoms”). Boolean operators will refine results, with English-language filters applied. Grey literature (e.g., ClinicalTrials.gov) will identify unpublished trials. Searches will be logged in Covidence software for transparency. Eligibility criteria This systematic review will include studies that meet the following criteria, structured according to the PICOS framework: the "Population," "Intervention," "Comparison," "Outcomes," and "Study Characteristics” 25 . Population Adults aged 18 and above diagnosed with MDD using standardised diagnostic criteria, specifically the Diagnostic and Statistical Manual of Mental Disorders, or the International Classification of Diseases, 10th Revision (ICD-10). The DSM-5, published by the American Psychiatric Association, defines MDD as the presence of at least five of nine symptoms (e.g., depressed mood, anhedonia, fatigue, guilt, impaired concentration) over two weeks, with at least one being depressed mood or loss of interest, causing significant distress or impairment 29 . The ICD-10, a WHO classification system, identifies MDD (codes F32/F33) through core symptoms (depressed mood, loss of interest, reduced energy) and additional symptoms (e.g., sleep disturbance, low self-esteem), with severity graded by symptom count and functional impact (e.g., mild 4 + symptoms, moderate 6+) 30 . These systems ensure diagnostic consistency across studies, with DSM-5 prevalent in North America and ICD-10 globally adopted, enhancing the review’s generalizability. Adolescents and children will be excluded due to potential developmental differences in their responses to the intervention 31 . Studies with mixed psychiatric diagnoses (e.g., MDD with bipolar disorder) are eligible only if MDD-specific data are isolable. Intervention Mindful breathing exercises (e.g., diaphragmatic breathing, deep breathing), either standalone or with separable effects if combined with other therapies (e.g., yoga). Comparison Standard care (e.g., pharmacotherapy), placebo (e.g., sham breathing), or no intervention. Outcomes The primary outcome is depressive symptom severity, measured using validated scales (e.g., Beck Depression Inventory [BDI], Hamilton Depression Rating Scale [HDRS], Patient Health Questionnaire-9 [PHQ-9]). Secondary outcomes include quality of life (e.g., SF-36) and psychological well-being (e.g., Ryff Scales). Exclusion criteria include studies without comparators, those with participants contraindicated for breathing exercises (e.g., severe respiratory conditions), or those lacking standardised MDD outcome measures. Non-peer-reviewed sources (e.g., preprints) will be excluded. Study selection Two reviewers (SA and NM) will independently screen titles and abstracts in Covidence, followed by full-text review against eligibility criteria. A third reviewer (BB) will resolve disputes. A PRISMA flow diagram will document the process, detailing the studies screened, included, and excluded, along with the reasons for exclusion. Risk of bias and quality assessment Risk of bias will be assessed using Cochrane RoB 2 for RCTs (randomisation, blinding, attrition) 28 and ROBINS-I for non-randomised studies (confounding, selection bias) 32 . Domains will be rated as low, high, or unclear risk, with overall study ratings assigned. Two supervisors (NM and BB) will conduct assessments, resolving disagreements via discussion. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will evaluate evidence quality across outcomes, considering the risk of bias, inconsistency, and precision 33 . High-bias studies may be excluded from meta-analysis or analysed separately. Data extraction A piloted form in Covidence will extract study characteristics (author, year, design, sample size), participant details (age, sex, MDD duration), intervention specifics (type, frequency, duration), comparator details, and outcome data (pre-and post-intervention scores, means, standard deviations). The two reviewers (SA and NM) will extract the data, with a third reviewer (BB) adjudicating any discrepancies. Missing data will prompt the author to contact us (via three attempts over a four-week period); unresolved cases will be excluded from the meta-analysis if key variables (e.g., effect sizes) are missing. Data synthesis Data synthesis will combine narrative and quantitative approaches, with a meta-analysis as the primary goal where data permit. A narrative synthesis will use thematic analysis to code study findings, identifying patterns in symptom reduction, quality of life improvements, and well-being outcomes. For the meta-analysis, a random-effects model will be employed in RevMan 5.4 to account for the expected heterogeneity across studies 34 . Effect measures will include: Mean Differences (MD) : For continuous outcomes (e.g., BDI scores) using the same scale, calculated as post-intervention differences between intervention and control groups. Standardised Mean Differences (SMD) : For outcomes measured with different scales (e.g., HDRS vs. PHQ-9), using Cohen’s d to standardise effects. Odds Ratios (OR) : For binary outcomes (e.g., remission rates), derived from dichotomous data where reported. Heterogeneity will be assessed using I² statistics and chi-squared tests, with I² >50% indicating substantial variability 35 . Sources of heterogeneity (e.g., intervention duration, comparator type) will be explored through subgroup analyses (e.g., short-term vs. long-term interventions) and sensitivity analyses that exclude studies with high-bias. Publication bias will be evaluated using funnel plots and Egger’s test if ≥ 10 studies are included 36 . If meta-analysis is unfeasible due to heterogeneity or insufficient data, a structured qualitative synthesis will summarise findings by outcome domain, supported by tables and narrative descriptions. Statistical significance will be set at α = 0.05, with confidence intervals (95%) reported for all effect estimates. Ethics and dissemination No ethical approval is required, as this review uses existing published data. Results will be submitted to a peer-reviewed journal in mental health or physiotherapy by late 2025, informing evidence-based MDD management. Data will be available upon request from the corresponding author. Protocol amendments will be documented with dates and rationales, reported in the final publication. Discussion This protocol for a systematic review and meta-analysis seeks to thoroughly assess the impact of mindful breathing exercises on alleviating symptoms, enhancing quality of life, and improving psychological well-being in individuals diagnosed with MDD. By consolidating existing evidence, this review aims to provide a detailed insight into the potential advantages and disadvantages of using mindful breathing as a supplementary intervention. The anticipated results are designed to guide clinicians, researchers, and policymakers in considering the incorporation of mindful breathing techniques into the treatment of MDD, potentially offering an affordable, easily accessible, and non-medicated approach to enhance patient outcomes. Additionally, this protocol emphasises the planned methodological rigour for the review, including clear eligibility criteria, a thorough literature search, and standardised procedures for data collection and analysis, all aimed at reducing bias and improving reproducibility. However, expected challenges, such as inconsistencies in intervention protocols, measures of outcomes, and the quality of studies, may restrict the applicability of the findings. These issues will be addressed through subgroup analyses and sensitivity analyses when applicable. Ultimately, this review will add to the body of evidence regarding non-pharmacological treatments for MDD and may inform future research, clinical practices, and policy formulation in the realm of mental health care. Declarations Author contributions : The authors contributed equally to the drafting and final version of the manuscript. Funding : This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Competing Interest : None declared. References Reiner RC, Olsen HE, Ikeda CT, et al. Diseases, injuries, and risk factors in child and adolescent health, 1990 to 2017: findings from the global burden of diseases, injuries, and risk factors 2017 study. JAMA Pediatr. 2019;173(6):e190337–37. Bains N, Abdijadid S. Major depressive disorder. 2020. American Psychiatric Association, Association A. AP. Diagnostic and statistical manual of mental disorders: DSM-IV. Washington, DC: American Psychiatric Association; 1994. Abdoli N, Salari N, Darvishi N, et al. The global prevalence of major depressive disorder (MDD) among the elderly: A systematic review and meta-analysis. Neurosci Biobehavioral Reviews. 2022;132:1067–73. Kieling C, Buchweitz C, Caye A, et al. Worldwide prevalence and disability from mental disorders across childhood and adolescence: evidence from the global burden of disease study. JAMA psychiatry. 2024;81(4):347–56. WHO. Improving Healthcare Quality in Europe: Characteristics, Effectiveness and Implementation of Different Strategies. Google Book: OECD Publishing; 2019. Gerber M, Beck J, Brand S, et al. The impact of lifestyle Physical Activity Counselling in IN-PATients with major depressive disorders on physical activity, cardiorespiratory fitness, depression, and cardiovascular health risk markers: study protocol for a randomized controlled trial. Trials. 2019;20:1–21. Liu J, Yan F, Ma X, et al. Prevalence of major depressive disorder and socio-demographic correlates: Results of a representative household epidemiological survey in Beijing, China. J Affect Disord. 2015;179:74–81. Nigussie K, Tesfaye D, Bete T, et al. Perceived stigma, common mental disorders and associated factors among primary caregivers of adult patients with mental illness attending at public hospitals, Harari regional state, Eastern Ethiopia: a multicenter cross-sectional study. Front Public Health. 2023;11:1024228. Patel V, Saxena S, Lund C, et al. The Lancet Commission on global mental health and sustainable development. Lancet. 2018;392(10157):1553–98. Kamenov K, Twomey C, Cabello M, et al. The efficacy of psychotherapy, pharmacotherapy and their combination on functioning and quality of life in depression: a meta-analysis. Psychol Med. 2017;47(3):414–25. Cuijpers P, Van Straten A, Andersson G, et al. Psychotherapy for depression in adults: a meta-analysis of comparative outcome studies. J Consult Clin Psychol. 2008;76(6):909. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905–17. Thornicroft G, Chatterji S, Evans-Lacko S, et al. Undertreatment of people with major depressive disorder in 21 countries. Br J Psychiatry. 2017;210(2):119–24. 10.1192/bjp.bp.116.188078 . [published Online First: 20161201]. Clement S, Schauman O, Graham T, et al. What is the impact of mental health-related stigma on help-seeking? A systematic review of quantitative and qualitative studies. Psychol Med. 2015;45(1):11–27. 10.1017/s0033291714000129 . [published Online First: 20140226]. Kabat-Zinn J. Full catastrophe living: Using the wisdom of your body and mind to face stress, pain, and illness, 15th anniversary ed. New York, NY, US: Delta Trade Paperback/Bantam Dell. 2005. Bentley TG, D’Andrea-Penna G, Rakic M, et al. Breathing practices for stress and anxiety reduction: Conceptual framework of implementation guidelines based on a systematic review of the published literature. Brain Sci. 2023;13(12):1612. Brown RP, Gerbarg PL. Sudarshan Kriya yogic breathing in the treatment of stress, anxiety, and depression: Part I—neurophysiologic model. J Altern Complement Med. 2005;11(1):189–201. Segal Z, Williams M, Teasdale J. Mindfulness-based cognitive therapy for depression. Guilford Press; 2012. Balban MY, Neri E, Kogon MM et al. Brief structured respiration practices enhance mood and reduce physiological arousal. Cell Rep Med 2023;4(1). Effect of mindfulness breathing meditation on. depression, anxiety, and stress: A randomized controlled trial among university students. Healthcare; 2022. Doll A, Hölzel BK, Bratec SM, et al. Mindful attention to breath regulates emotions via increased amygdala–prefrontal cortex connectivity. NeuroImage. 2016;134:305–13. Brush C, Hajcak G, Bocchine AJ, et al. A randomised trial of aerobic exercise for major depression: examining neural indicators of reward and cognitive control as predictors and treatment targets. Psychol Med. 2022;52(5):893–903. Calisgan E, Cumurcu HB, Talu B, et al. The effects of physiotherapy methods combined with respiratory and relaxation exercises on patients with major depression. Medicine. 2020;9(4):837–43. Hofmann SG, Sawyer AT, Witt AA, et al. The effect of mindfulness-based therapy on anxiety and depression: A meta-analytic review. J Consult Clin Psychol. 2010;78(2):169. Miller KJ, Goncalves-Bradley DC, Areerob P, et al. Comparative effectiveness of three exercise types to treat clinical depression in older adults: A systematic review and network meta-analysis of randomised controlled trials. Ageing Res Rev. 2020;58:100999. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Reviews. 2015;4(1):1. 10.1186/2046-4053-4-1 . Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. 10.1136/bmj.d5928 . American Psychiatric Association A. Diagnostic and statistical manual of mental disorders: DSM-IV. Washington, DC: American Psychiatric Association; 1994. WHO. International statistical classification of diseases and related health problems: 10th revision (ICD-10). http://www who int/classifications/apps/icd/ icd 1992. Zalsman G, Brent DA, Weersing VR. Depressive disorders in childhood and adolescence: an overview: epidemiology, clinical manifestation and risk factors. Child Adolesc Psychiatric Clin. 2006;15(4):827–41. Sterne JA, Hernán MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. 10.1136/bmj.i4919 . Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating the quality of evidence and the strength of recommendations. BMJ. 2008;336(7650):924–26. Borenstein M, Hedges LV, Higgins JP et al. Introduction to meta-analysis: Wiley 2021. Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60. Egger M, Smith GD, Schneider M et al. Bias in meta-analysis detected by a simple, graphical test. bmj 1997;315(7109):629 – 34. Supplementary Files PRISMAPchecklist.pdf Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 07 Jan, 2026 Reviewers agreed at journal 15 Dec, 2025 Reviewers invited by journal 03 Dec, 2025 Editor assigned by journal 30 Nov, 2025 First submitted to journal 09 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7820951","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":554876933,"identity":"21475b14-1607-4f4c-a411-fa4a50a8da4f","order_by":0,"name":"Saad Bin Muaythir","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYJACaSDmYWBmPgCkJWSI1JLAIMPAzpYA0sJDtBYbBn4eAwawdYSAfPvhh7cLf9jxGBzm+fzqRo0FDwP74aMb8GkxOJNmbD0jIZlHspl3m3XOMaDDeNLSbuDVwpBgJs2TcICHn5l3m3EOG1CLBI8ZXi3y/c+/gbWwMfM8M875R4QWhhs5MFt4mB/nthGhxeDGm2JrnjSQX9jMmHP7JHjYCPlFvj99420eGzt7g/OHH3/O+VYnx89++Bh+hyEBNgkwSaxyEGD+QIrqUTAKRsEoGDkAAM/5PUalOzD7AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-1498-4752","institution":"University of Pretoria","correspondingAuthor":true,"prefix":"","firstName":"Saad","middleName":"Bin","lastName":"Muaythir","suffix":""},{"id":554876934,"identity":"8a694b27-3187-49a5-a571-bb6d3b365e12","order_by":1,"name":"Nombeko Mshunqane","email":"","orcid":"","institution":"University of Kwazulu-Natal","correspondingAuthor":false,"prefix":"","firstName":"Nombeko","middleName":"","lastName":"Mshunqane","suffix":""},{"id":554876935,"identity":"46b7dd17-8bff-4b97-9df5-a17a2af8f01e","order_by":2,"name":"Bashir Bello","email":"","orcid":"","institution":"Bayero University","correspondingAuthor":false,"prefix":"","firstName":"Bashir","middleName":"","lastName":"Bello","suffix":""},{"id":554876936,"identity":"f3b76a02-4cbd-4ffd-a3c8-f2ae7c6bb0e6","order_by":3,"name":"Enos Ramano","email":"","orcid":"","institution":"University of Pretoria","correspondingAuthor":false,"prefix":"","firstName":"Enos","middleName":"","lastName":"Ramano","suffix":""},{"id":554876937,"identity":"8eac8f84-d40b-48d5-9e3c-36c51d83df37","order_by":4,"name":"Nontembiso Magida","email":"","orcid":"","institution":"University of Pretoria","correspondingAuthor":false,"prefix":"","firstName":"Nontembiso","middleName":"","lastName":"Magida","suffix":""}],"badges":[],"createdAt":"2025-10-09 21:26:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7820951/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7820951/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97535319,"identity":"61e4d2dc-2763-49d5-b55f-a2da940e0cca","added_by":"auto","created_at":"2025-12-05 14:05:59","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":9421,"visible":true,"origin":"","legend":"","description":"","filename":"sysrSYSRD2501377.xml","url":"https://assets-eu.researchsquare.com/files/rs-7820951/v1/6879dbe71353f207c348322e.xml"},{"id":97535316,"identity":"2d7cc90b-b6de-419b-a5f1-08cb555ad74b","added_by":"auto","created_at":"2025-12-05 14:05:58","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1042,"visible":true,"origin":"","legend":"","description":"","filename":"SYSRD250137723583.go.xml","url":"https://assets-eu.researchsquare.com/files/rs-7820951/v1/02e15655123e11dc522eec48.xml"},{"id":97535317,"identity":"abdfb6c8-dea5-46ff-b427-551e6880185d","added_by":"auto","created_at":"2025-12-05 14:05:59","extension":"xml","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":915,"visible":true,"origin":"","legend":"","description":"","filename":"SYSRD2501377Import.xml","url":"https://assets-eu.researchsquare.com/files/rs-7820951/v1/ea663d956fc74be58a76b6b1.xml"},{"id":97535320,"identity":"3e69e75e-f1a7-4990-bc27-ac7b608598df","added_by":"auto","created_at":"2025-12-05 14:05:59","extension":"xml","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":71452,"visible":true,"origin":"","legend":"","description":"","filename":"SYSRD25013770enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7820951/v1/50d777f7f13b787804e47497.xml"},{"id":97535318,"identity":"e339a201-c988-4961-a0d3-8ea765caf4f6","added_by":"auto","created_at":"2025-12-05 14:05:59","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":69934,"visible":true,"origin":"","legend":"","description":"","filename":"SYSRD25013770structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7820951/v1/0a6c53c34d2291c676b3e185.xml"},{"id":97670987,"identity":"eb0bcafb-820f-40ab-8337-e7be8da28694","added_by":"auto","created_at":"2025-12-08 09:31:41","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":78174,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7820951/v1/302aa032308550a0e6107f20.html"},{"id":97677753,"identity":"8f3803bc-4550-4493-9371-b5db44ca1171","added_by":"auto","created_at":"2025-12-08 09:54:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":524794,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7820951/v1/bea4efaa-95d1-49ca-8e2b-9e765629cca1.pdf"},{"id":97535321,"identity":"dca7a812-1c49-4d90-abc6-8be61e89d743","added_by":"auto","created_at":"2025-12-05 14:05:59","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":121726,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMAPchecklist.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7820951/v1/c9f92edf9feea0d8b47beb45.pdf"}],"financialInterests":"","formattedTitle":"Effectiveness of Mindful Breathing Exercises on Symptom Reduction, quality of life, and Psychological Well-being in Individuals with Major Depressive Disorder: A Systematic Review and Meta-analysis Protocol","fulltext":[{"header":"Strengths and Limitations of This Study ","content":"\u003cul\u003e\n \u003cli\u003eThis protocol follows PRISMA-P guidelines and Cochrane methodology, which ensures a rigorous, transparent and reproducible systematic review process.\u003c/li\u003e\n \u003cli\u003eMindful breathing exercises are inexpensive, simple to use, and widely available. Particularly in environments with limited resources, assessing the efficacy of these approaches provides valuable information for mental health treatment.\u003c/li\u003e\n \u003cli\u003eThe review will provide a more comprehensive understanding of patient-centred outcomes by evaluating quality of life and well-being in addition to the reduction of symptoms associated with MDD.\u003c/li\u003e\n \u003cli\u003eThe exclusion of non-English studies may introduce language bias, potentially missing relevant evidence from diverse settings. This could create a limitation of the study.\u003c/li\u003e\n \u003cli\u003eHeterogeneity may be introduced by differences in the kind, length, frequency, and mode of delivery of mindful breathing interventions among studies, making direct comparisons and meta-analytical pooling more difficult.\u003c/li\u003e\n \u003cli\u003eStudies with positive results are more likely to be published than those with null or negative results, which could skew the review\u0026apos;s findings.\u003c/li\u003e\n\u003c/ul\u003e\n"},{"header":"Introduction","content":"\u003cp\u003ePsychiatric disorders impose a significant global health burden, with major depressive disorder (MDD) standing out as a primary contributor to disability. The Global Burden of Disease study identifies depression as one of the top ten causes of years lost to disability (YLD) in high-income countries, a reflection of its widespread prevalence and debilitating effects\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. MDD is characterised by persistent low mood, anhedonia (loss of interest or pleasure), fatigue, excessive guilt, low self-esteem, disrupted sleep or appetite, and impaired cognitive function, as delineated in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR)\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. These symptoms distinguish MDD from other psychiatric conditions like schizophrenia or bipolar disorder. Yet, its global prevalence, estimated at 13.3% among adults and over 10% in children, marks it as a uniquely pervasive challenge \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The World Health Organisation (WHO) projects that by 2030, MDD will surpass all other conditions to become the leading cause of disability worldwide, highlighting the critical need for effective, scalable interventions \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eBeyond its symptomatic toll, MDD profoundly impacts health-related quality of life (HRQoL). Research consistently shows that individuals with MDD experience reduced physical, social, and emotional functioning, often exacerbated by comorbidities such as anxiety, substance use disorders, or chronic physical illnesses like diabetes\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. This multidimensional burden contributes to substantial disability-adjusted life years (DALYs) and premature mortality, which is straining healthcare systems globally \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. In high-income settings, where mental health resources are relatively accessible, the persistence of MDD-related disability suggests gaps in current treatment approaches \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. In low- and middle-income countries, these gaps widen due to limited infrastructure, amplifying the public health crisis\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Consequently, addressing MDD requires innovative strategies that complement existing therapies and bridge accessibility barriers.\u003c/p\u003e\u003cp\u003eStandard MDD management relies on pharmacotherapy (e.g., selective serotonin reuptake inhibitors [SSRIs]) and psychotherapy (e.g., cognitive-behavioral therapy [CBT], interpersonal therapy [IPT]), which are supported by robust evidence \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. Meta-analyses, such as that by Cuijpers et al. (2008), report moderate to large effect sizes for these interventions in reducing depressive symptoms; however, their limitations are well recognised\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Up to 50% of patients exhibit partial or no response to antidepressants, with side effects like weight gain or emotional numbing deterring adherence \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Psychotherapy, while effective, demands trained providers and sustained patient engagement, often impractical in resource-scarce settings or for those facing logistical or stigma-related barriers, like in Saudi Arabia\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. These challenges have fueled interest in non-pharmacological alternatives, particularly mindfulness-based interventions, which capitalise on the interplay between emotional regulation, lifestyle, and resilience\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eMindful breathing exercises, a focused subset of mindfulness practices, involve structured techniques, such as diaphragmatic breathing, deep breathing, or breath counting, to enhance present-moment awareness and regulate emotional responses \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. By activating the parasympathetic nervous system, these exercises reduce sympathetic arousal, countering the physiological stress response that is central to MDD\u0026rsquo;s pathology\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Unlike comprehensive mindfulness programs, which blend meditation, body awareness, and cognitive strategies, mindful breathing offers a standalone, accessible practice requires minimal training\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. Preliminary studies suggest that it may reduce depressive symptoms, improve HRQoL, and enhance psychological well-being, potentially through mechanisms such as increased vagal tone or modulated amygdala-prefrontal cortex connectivity \u003csup\u003e\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. However, the evidence is inconsistent, with many trials embedding breathing within broader interventions or lacking rigorous controls \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eExisting systematic reviews have explored mindfulness-based therapies for depression, but rarely isolate mindful breathing\u0026rsquo;s specific effects\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. A comprehensive meta-analysis that included a range of mindfulness practices was performed, which consequently restricted its relevance to interventions centred solely on breathing\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Additionally, a review of exercise therapies was conducted that completely overlooked this particular technique\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Given the heterogeneity of MDD and the potential of mindful breathing as a low-cost, scalable adjunct, a targeted systematic review with meta-analysis is warranted. This protocol aims to synthesise evidence on the effects of mindful breathing exercises on depressive symptom severity, quality of life, and psychological well-being in adults with MDD, using meta-analytic techniques to quantify intervention efficacy and guide clinical practice.\u003c/p\u003e"},{"header":"Methods and analysis","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003eQuantitative RCTs and controlled observational studies in English, with no publication year restriction. This systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, ensuring transparency and reproducibility\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. It will adopt Cochrane methodology for systematic reviews of interventions, incorporating a meta-analysis to provide a quantitative synthesis where feasible\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. The review is registered on PROSPERO (CRD420251032845) to enhance accountability and minimise duplication. It will include quantitative studies, such as experimental studies, to evaluate the impact of mindful breathing exercises on MDD outcomes. This protocol began the literature search from September 2025, with data extraction anticipated to be completed by December 2025.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSearch strategy\u003c/h3\u003e\n\u003cp\u003eA comprehensive search, conducted in collaboration with an information specialist, will target the Cochrane Library, Medline (via PubMed), PEDro, CINAHL, Scopus, Web of Science, and BioMed Central, spanning from inception to September 2025. Search terms will combine Medical Subject Headings (MeSH) and free-text: (\u0026ldquo;Major Depressive Disorder\u0026rdquo; OR \u0026ldquo;Depression\u0026rdquo;) AND (\u0026ldquo;Mindful Breathing\u0026rdquo; OR \u0026ldquo;Breathing Exercises\u0026rdquo;) AND (\u0026ldquo;Quality of Life\u0026rdquo; OR \u0026ldquo;Depressive Symptoms\u0026rdquo;). Boolean operators will refine results, with English-language filters applied. Grey literature (e.g., ClinicalTrials.gov) will identify unpublished trials. Searches will be logged in Covidence software for transparency.\u003c/p\u003e\n\u003ch3\u003eEligibility criteria\u003c/h3\u003e\n\u003cp\u003eThis systematic review will include studies that meet the following criteria, structured according to the PICOS framework: the \"Population,\" \"Intervention,\" \"Comparison,\" \"Outcomes,\" and \"Study Characteristics\u0026rdquo;\u003csup\u003e25\u003c/sup\u003e.\u003c/p\u003e\n\u003ch3\u003ePopulation\u003c/h3\u003e\n\u003cp\u003eAdults aged 18 and above diagnosed with MDD using standardised diagnostic criteria, specifically the Diagnostic and Statistical Manual of Mental Disorders, or the International Classification of Diseases, 10th Revision (ICD-10). The DSM-5, published by the American Psychiatric Association, defines MDD as the presence of at least five of nine symptoms (e.g., depressed mood, anhedonia, fatigue, guilt, impaired concentration) over two weeks, with at least one being depressed mood or loss of interest, causing significant distress or impairment\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. The ICD-10, a WHO classification system, identifies MDD (codes F32/F33) through core symptoms (depressed mood, loss of interest, reduced energy) and additional symptoms (e.g., sleep disturbance, low self-esteem), with severity graded by symptom count and functional impact (e.g., mild 4\u0026thinsp;+\u0026thinsp;symptoms, moderate 6+)\u003csup\u003e30\u003c/sup\u003e. These systems ensure diagnostic consistency across studies, with DSM-5 prevalent in North America and ICD-10 globally adopted, enhancing the review\u0026rsquo;s generalizability. Adolescents and children will be excluded due to potential developmental differences in their responses to the intervention\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Studies with mixed psychiatric diagnoses (e.g., MDD with bipolar disorder) are eligible only if MDD-specific data are isolable.\u003c/p\u003e\n\u003ch3\u003eIntervention\u003c/h3\u003e\n\u003cp\u003eMindful breathing exercises (e.g., diaphragmatic breathing, deep breathing), either standalone or with separable effects if combined with other therapies (e.g., yoga).\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eComparison\u003c/h2\u003e\u003cp\u003eStandard care (e.g., pharmacotherapy), placebo (e.g., sham breathing), or no intervention.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome is depressive symptom severity, measured using validated scales (e.g., Beck Depression Inventory [BDI], Hamilton Depression Rating Scale [HDRS], Patient Health Questionnaire-9 [PHQ-9]). Secondary outcomes include quality of life (e.g., SF-36) and psychological well-being (e.g., Ryff Scales). Exclusion criteria include studies without comparators, those with participants contraindicated for breathing exercises (e.g., severe respiratory conditions), or those lacking standardised MDD outcome measures. Non-peer-reviewed sources (e.g., preprints) will be excluded.\u003c/p\u003e\n\u003ch3\u003eStudy selection\u003c/h3\u003e\n\u003cp\u003eTwo reviewers (SA and NM) will independently screen titles and abstracts in Covidence, followed by full-text review against eligibility criteria. A third reviewer (BB) will resolve disputes. A PRISMA flow diagram will document the process, detailing the studies screened, included, and excluded, along with the reasons for exclusion.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eRisk of bias and quality assessment\u003c/h2\u003e\u003cp\u003eRisk of bias will be assessed using Cochrane RoB 2 for RCTs (randomisation, blinding, attrition)\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e and ROBINS-I for non-randomised studies (confounding, selection bias)\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. Domains will be rated as low, high, or unclear risk, with overall study ratings assigned. Two supervisors (NM and BB) will conduct assessments, resolving disagreements via discussion. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will evaluate evidence quality across outcomes, considering the risk of bias, inconsistency, and precision\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e. High-bias studies may be excluded from meta-analysis or analysed separately.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eData extraction\u003c/h2\u003e\u003cp\u003eA piloted form in Covidence will extract study characteristics (author, year, design, sample size), participant details (age, sex, MDD duration), intervention specifics (type, frequency, duration), comparator details, and outcome data (pre-and post-intervention scores, means, standard deviations). The two reviewers (SA and NM) will extract the data, with a third reviewer (BB) adjudicating any discrepancies. Missing data will prompt the author to contact us (via three attempts over a four-week period); unresolved cases will be excluded from the meta-analysis if key variables (e.g., effect sizes) are missing.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eData synthesis\u003c/h2\u003e\u003cp\u003eData synthesis will combine narrative and quantitative approaches, with a meta-analysis as the primary goal where data permit. A narrative synthesis will use thematic analysis to code study findings, identifying patterns in symptom reduction, quality of life improvements, and well-being outcomes. For the meta-analysis, a random-effects model will be employed in RevMan 5.4 to account for the expected heterogeneity across studies\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e. Effect measures will include:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eMean Differences (MD)\u003c/b\u003e: For continuous outcomes (e.g., BDI scores) using the same scale, calculated as post-intervention differences between intervention and control groups.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eStandardised Mean Differences (SMD)\u003c/b\u003e: For outcomes measured with different scales (e.g., HDRS vs. PHQ-9), using Cohen\u0026rsquo;s d to standardise effects.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eOdds Ratios (OR)\u003c/b\u003e: For binary outcomes (e.g., remission rates), derived from dichotomous data where reported.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003eHeterogeneity will be assessed using I\u0026sup2; statistics and chi-squared tests, with I\u0026sup2; \u0026gt;50% indicating substantial variability \u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. Sources of heterogeneity (e.g., intervention duration, comparator type) will be explored through subgroup analyses (e.g., short-term vs. long-term interventions) and sensitivity analyses that exclude studies with high-bias. Publication bias will be evaluated using funnel plots and Egger\u0026rsquo;s test if\u0026thinsp;\u0026ge;\u0026thinsp;10 studies are included\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e. If meta-analysis is unfeasible due to heterogeneity or insufficient data, a structured qualitative synthesis will summarise findings by outcome domain, supported by tables and narrative descriptions. Statistical significance will be set at α\u0026thinsp;=\u0026thinsp;0.05, with confidence intervals (95%) reported for all effect estimates.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eEthics and dissemination\u003c/h2\u003e\u003cp\u003eNo ethical approval is required, as this review uses existing published data. Results will be submitted to a peer-reviewed journal in mental health or physiotherapy by late 2025, informing evidence-based MDD management. Data will be available upon request from the corresponding author. Protocol amendments will be documented with dates and rationales, reported in the final publication.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis protocol for a systematic review and meta-analysis seeks to thoroughly assess the impact of mindful breathing exercises on alleviating symptoms, enhancing quality of life, and improving psychological well-being in individuals diagnosed with MDD. By consolidating existing evidence, this review aims to provide a detailed insight into the potential advantages and disadvantages of using mindful breathing as a supplementary intervention. The anticipated results are designed to guide clinicians, researchers, and policymakers in considering the incorporation of mindful breathing techniques into the treatment of MDD, potentially offering an affordable, easily accessible, and non-medicated approach to enhance patient outcomes. Additionally, this protocol emphasises the planned methodological rigour for the review, including clear eligibility criteria, a thorough literature search, and standardised procedures for data collection and analysis, all aimed at reducing bias and improving reproducibility. However, expected challenges, such as inconsistencies in intervention protocols, measures of outcomes, and the quality of studies, may restrict the applicability of the findings. These issues will be addressed through subgroup analyses and sensitivity analyses when applicable. Ultimately, this review will add to the body of evidence regarding non-pharmacological treatments for MDD and may inform future research, clinical practices, and policy formulation in the realm of mental health care.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e: The authors contributed equally to the drafting and final version of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interest\u003c/strong\u003e: \u0026nbsp;None declared.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eReiner RC, Olsen HE, Ikeda CT, et al. Diseases, injuries, and risk factors in child and adolescent health, 1990 to 2017: findings from the global burden of diseases, injuries, and risk factors 2017 study. JAMA Pediatr. 2019;173(6):e190337\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBains N, Abdijadid S. Major depressive disorder. 2020.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmerican Psychiatric Association, Association A. AP. Diagnostic and statistical manual of mental disorders: DSM-IV. Washington, DC: American Psychiatric Association; 1994.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAbdoli N, Salari N, Darvishi N, et al. The global prevalence of major depressive disorder (MDD) among the elderly: A systematic review and meta-analysis. Neurosci Biobehavioral Reviews. 2022;132:1067\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKieling C, Buchweitz C, Caye A, et al. Worldwide prevalence and disability from mental disorders across childhood and adolescence: evidence from the global burden of disease study. JAMA psychiatry. 2024;81(4):347\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWHO. Improving Healthcare Quality in Europe: Characteristics, Effectiveness and Implementation of Different Strategies. Google Book: OECD Publishing; 2019.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGerber M, Beck J, Brand S, et al. The impact of lifestyle Physical Activity Counselling in IN-PATients with major depressive disorders on physical activity, cardiorespiratory fitness, depression, and cardiovascular health risk markers: study protocol for a randomized controlled trial. Trials. 2019;20:1\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu J, Yan F, Ma X, et al. Prevalence of major depressive disorder and socio-demographic correlates: Results of a representative household epidemiological survey in Beijing, China. J Affect Disord. 2015;179:74\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNigussie K, Tesfaye D, Bete T, et al. Perceived stigma, common mental disorders and associated factors among primary caregivers of adult patients with mental illness attending at public hospitals, Harari regional state, Eastern Ethiopia: a multicenter cross-sectional study. Front Public Health. 2023;11:1024228.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePatel V, Saxena S, Lund C, et al. The Lancet Commission on global mental health and sustainable development. Lancet. 2018;392(10157):1553\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKamenov K, Twomey C, Cabello M, et al. The efficacy of psychotherapy, pharmacotherapy and their combination on functioning and quality of life in depression: a meta-analysis. Psychol Med. 2017;47(3):414\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCuijpers P, Van Straten A, Andersson G, et al. Psychotherapy for depression in adults: a meta-analysis of comparative outcome studies. J Consult Clin Psychol. 2008;76(6):909.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eThornicroft G, Chatterji S, Evans-Lacko S, et al. Undertreatment of people with major depressive disorder in 21 countries. Br J Psychiatry. 2017;210(2):119\u0026ndash;24. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1192/bjp.bp.116.188078\u003c/span\u003e\u003cspan address=\"10.1192/bjp.bp.116.188078\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. [published Online First: 20161201].\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eClement S, Schauman O, Graham T, et al. What is the impact of mental health-related stigma on help-seeking? A systematic review of quantitative and qualitative studies. Psychol Med. 2015;45(1):11\u0026ndash;27. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1017/s0033291714000129\u003c/span\u003e\u003cspan address=\"10.1017/s0033291714000129\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. [published Online First: 20140226].\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKabat-Zinn J. Full catastrophe living: Using the wisdom of your body and mind to face stress, pain, and illness, 15th anniversary ed. New York, NY, US: Delta Trade Paperback/Bantam Dell. 2005.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBentley TG, D\u0026rsquo;Andrea-Penna G, Rakic M, et al. Breathing practices for stress and anxiety reduction: Conceptual framework of implementation guidelines based on a systematic review of the published literature. Brain Sci. 2023;13(12):1612.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrown RP, Gerbarg PL. Sudarshan Kriya yogic breathing in the treatment of stress, anxiety, and depression: Part I\u0026mdash;neurophysiologic model. J Altern Complement Med. 2005;11(1):189\u0026ndash;201.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSegal Z, Williams M, Teasdale J. Mindfulness-based cognitive therapy for depression. Guilford Press; 2012.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBalban MY, Neri E, Kogon MM et al. Brief structured respiration practices enhance mood and reduce physiological arousal. Cell Rep Med 2023;4(1).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEffect of mindfulness breathing meditation on. depression, anxiety, and stress: A randomized controlled trial among university students. Healthcare; 2022.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDoll A, H\u0026ouml;lzel BK, Bratec SM, et al. Mindful attention to breath regulates emotions via increased amygdala\u0026ndash;prefrontal cortex connectivity. NeuroImage. 2016;134:305\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBrush C, Hajcak G, Bocchine AJ, et al. A randomised trial of aerobic exercise for major depression: examining neural indicators of reward and cognitive control as predictors and treatment targets. Psychol Med. 2022;52(5):893\u0026ndash;903.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCalisgan E, Cumurcu HB, Talu B, et al. The effects of physiotherapy methods combined with respiratory and relaxation exercises on patients with major depression. Medicine. 2020;9(4):837\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHofmann SG, Sawyer AT, Witt AA, et al. The effect of mindfulness-based therapy on anxiety and depression: A meta-analytic review. J Consult Clin Psychol. 2010;78(2):169.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMiller KJ, Goncalves-Bradley DC, Areerob P, et al. Comparative effectiveness of three exercise types to treat clinical depression in older adults: A systematic review and network meta-analysis of randomised controlled trials. Ageing Res Rev. 2020;58:100999.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMoher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Reviews. 2015;4(1):1. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/2046-4053-4-1\u003c/span\u003e\u003cspan address=\"10.1186/2046-4053-4-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHiggins JPT, Altman DG, G\u0026oslash;tzsche PC, et al. The Cochrane Collaboration\u0026rsquo;s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj.d5928\u003c/span\u003e\u003cspan address=\"10.1136/bmj.d5928\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmerican Psychiatric Association A. Diagnostic and statistical manual of mental disorders: DSM-IV. Washington, DC: American Psychiatric Association; 1994.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWHO. International statistical classification of diseases and related health problems: 10th revision (ICD-10). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www who int/classifications/apps/icd/\u003c/span\u003e\u003cspan address=\"http://www who int/classifications/apps/icd/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cem\u003eicd\u003c/em\u003e 1992.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZalsman G, Brent DA, Weersing VR. Depressive disorders in childhood and adolescence: an overview: epidemiology, clinical manifestation and risk factors. Child Adolesc Psychiatric Clin. 2006;15(4):827\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSterne JA, Hern\u0026aacute;n MA, Reeves BC, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj.i4919\u003c/span\u003e\u003cspan address=\"10.1136/bmj.i4919\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGuyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating the quality of evidence and the strength of recommendations. BMJ. 2008;336(7650):924\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBorenstein M, Hedges LV, Higgins JP et al. Introduction to meta-analysis: Wiley 2021.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHiggins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEgger M, Smith GD, Schneider M et al. Bias in meta-analysis detected by a simple, graphical test. \u003cem\u003ebmj\u003c/em\u003e 1997;315(7109):629\u0026thinsp;\u0026ndash;\u0026thinsp;34.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Mindful breathing exercises, major depressive disorders, quality of life, psychological well-being","lastPublishedDoi":"10.21203/rs.3.rs-7820951/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7820951/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eIntroduction\u003c/p\u003e\u003cp\u003eMajor depressive disorder (MDD) is a prevalent mental health condition marked by persistent sadness, loss of interest, and impaired cognition, significantly affecting quality of life. While pharmacotherapy and psychotherapy are standard treatments, non-pharmacological interventions like mindful breathing exercises have gained attention for their potential to reduce depressive symptoms and enhance well-being. Despite some evidence of effectiveness, a comprehensive, up-to-date synthesis focusing solely on mindful breathing in MDD is lacking. This systematic review protocol will evaluate the impact of mindful breathing exercises on depressive symptom severity, quality of life, and psychological well-being in adults with MDD.\u003c/p\u003e\u003cp\u003eMethods and analysis\u003c/p\u003e\u003cp\u003eThis review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2015 checklists. A comprehensive search of Cochrane, Medline, PEDro, CINAHL, Scopus, Web of Science, and BioMed Central will be carried out from inception to April 2025. Using the PICOs framework, we will include quantitative studies (randomised controlled trials and controlled observational designs) involving adults aged 18 and above who have been diagnosed with MDD using standardised criteria (e.g., DSM-5, ICD-10). Three reviewers will independently screen titles, abstracts, and full texts and extract data using the COVIDENCE software. The risk of Bias Assessment will be conducted using Cochrane RoB 2 (RCTs) and ROBINS-I (non-randomised studies), and the evidence quality will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. A meta-analysis using RevMan 5.4 will pool mean differences, standardised mean differences, or odds ratios if data permit; otherwise, a narrative synthesis will be conducted. The search began in September 2025, with completion anticipated by December 2025.\u003c/p\u003e\u003cp\u003eEthics and dissemination\u003c/p\u003e\u003cp\u003eNo ethical approval is required as this review uses existing published data. Findings will be disseminated through a peer-reviewed journal and presented at academic conferences.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePROSPERO registration\u003c/b\u003e: CRD420251032845\u003c/p\u003e","manuscriptTitle":"Effectiveness of Mindful Breathing Exercises on Symptom Reduction, quality of life, and Psychological Well-being in Individuals with Major Depressive Disorder: A Systematic Review and Meta-analysis Protocol","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-05 14:05:54","doi":"10.21203/rs.3.rs-7820951/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2026-01-08T03:30:34+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-12-15T17:37:39+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-03T20:21:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-01T02:53:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"Systematic Reviews","date":"2025-10-09T17:26:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"systematic-reviews","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sysr","sideBox":"Learn more about [Systematic Reviews](http://systematicreviewsjournal.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/sysr/default.aspx","title":"Systematic Reviews","twitterHandle":"@MedicalEvidence","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"67832567-8f2c-4f36-8e4d-9fa22b7c554c","owner":[],"postedDate":"December 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-19T08:35:48+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-05 14:05:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7820951","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7820951","identity":"rs-7820951","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}