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Challenges Establishing the Efficacy of Exercise as an Antidepressant Treatment: A Systematic Review and Meta-Analysis of Control Group Responses in Exercise Randomised Controlled Trials

Sports Medicine volume 46, pages 699–713 (2016)Cite this article

Abstract

Background

Whilst previous meta-analyses have demonstrated that control group responses (CGRs) can negatively influence antidepressant efficacy, no such meta-analysis exists in exercise randomised controlled trials (RCTs).

Objective

The aim of this study was to conduct a systematic review and meta-analysis investigating CGRs and predictors in control groups of exercise RCTs among adults with depression.

Methods

Three authors acquired RCTs from a previous Cochrane review (2013) and conducted updated searches of major databases from January 2013 to August 2015. We included exercise RCTs that (1) involved adults with major depressive disorder (MDD) or depressive symptoms; (2) measured depressive symptoms pre- and post-intervention using a validated measure [e.g. Hamilton Depression Scale (HAM-D)]; and (3) included a non-active control group. A random effects meta-analysis calculating the standardised mean difference (SMD) together with 95 % confidence intervals (CIs) was employed to determine CGR.

Results

Across 41 studies, 1122 adults with depression were included [mean (SD) age 50 (18) years, 63 % female]. A large CGR of improved depressive symptoms was evident across all studies (SMD −0.920, 95 % CI −1.11 to −0.729). CGRs were elevated across all subgroup analyses, including high quality studies (n = 11, SMD −1.430, 95 % CI −1.771 to −1.090) and MDD participants (n = 18, SMD −1.248, 95 % CI = −1.585 to −0.911). The CGR equated to an improvement of −7.5 points on the HAM-D (95 % CI −10.30 to −4.89). In MDD participants, increasing age moderated a smaller CGR, while the percentage of drop-outs, baseline depressive symptoms and a longer control group duration moderated a larger CGR (i.e. improvement) (p < 0.05).

Conclusion

In order to demonstrate effectiveness, exercise has to overcome a powerful CGR of approximately double that reported for antidepressant RCTS.

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References

  1. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015; 386(9995):743–800.

  2. Ferrari AJ, Charlson FJ, Norman RE, et al. Burden of depressive disorders by country, sex, age, and year: findings from the Global Burden of Disease Study 2010. PLoS Med. 2013;10(11):1–12.

    Article  Google Scholar 

  3. Warden D, Rush AJ, Trivedi MH, et al. The STAR*D Project results: a comprehensive review of findings. Curr Psychiatry Rep. 2007;9(6):449–59.

    Article  PubMed  Google Scholar 

  4. Knapen J, Vancampfort D, Moriën Y, et al. Exercise therapy improves both mental and physical health in patients with major depression. Disabil Rehabil. 2015;37(16):1490–5.

    Article  PubMed  Google Scholar 

  5. Vancampfort D, Stubbs B, Ward PB, et al. Integrating physical activity as medicine in the care of people with severe mental illness. Aust N Z J Psychiatry. 2015;49(8):681–2.

    Article  PubMed  Google Scholar 

  6. Rethorst CD, Wipfli BM, Landers DM. The antidepressive effects of exercise: a meta-analysis of randomized trials. Sports Med. 2009;39(6):491–511.

    Article  PubMed  Google Scholar 

  7. Cleare A, Pariante CM, Young AH, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015;29(5):459–525.

    CAS  Article  PubMed  Google Scholar 

  8. Vancampfort D, Mitchell AJ, de Hert M, et al. Type 2 diabetes in patients with major depressive disorder: a meta-analysis of prevalence estimates and predictors. Depress Anxiety. 2015;32(10):763–73.

    Article  PubMed  Google Scholar 

  9. Holt RIG, de Groot M, Lucki I, et al. NIDDK International conference report on diabetes and depression: current understanding and future directions. Diabetes Care. 2014;37(8):2067–77.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Naci H, Ioannidis JPA. Comparative effectiveness of exercise and drug interventions on mortality outcomes: metaepidemiological study. BMJ. 2013;347:f5577.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Dugan SA, Bromberger JT, Eisuke S, et al. Association between physical activity and depressive symptoms: midlife women in SWAN. Med Sci Sports Exerc. 2015;47(2):335–42.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Schuch FB, Vasconcelos-Moreno MP, Borowsky C, et al. Exercise and severe major depression: effect on symptom severity and quality of life at discharge in an inpatient cohort. J Psychiatry Res. 2015;61:25–32.

    CAS  Article  Google Scholar 

  13. Chalder M, Wiles NJ, Campbell J, et al. Facilitated physical activity as a treatment for depressed adults: randomised controlled trial. BMJ. 2012;344:e2758.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Krogh J, Videbech P, Thomsen C, et al. DEMO-II trial. Aerobic exercise versus stretching exercise in patients with major depression-a randomised clinical trial. PLoS One. 2012;7(10):e48316.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Papakostas GI, Østergaard SD, Iovieno N. The nature of placebo response in clinical studies of major depressive disorder. J Clin Psychiatry. 2015;76(4):456–66.

    Article  PubMed  Google Scholar 

  16. Schuch FB, Fleck MP. Is exercise an efficacious treatment for depression? A comment upon recent negative findings. Front Psychiatry. 2013;4:20.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Rutherford BR, Mori S, Sneed JR, et al. Contribution of spontaneous improvement to placebo response in depression: a meta-analytic review. J Psychiatr Res. 2012;46(6):697–702.

  18. Rutherford BR, Roose SP. A model of placebo response in antidepressant clinical trials. Am J Psychiatry. 2013;170(7):723–33.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Brunoni AR, Lopes M, Kaptchuk TJ, et al. Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis. PLoS One. 2009;4(3):1–10.

    Article  Google Scholar 

  20. Lindheimer J, O’Connor P, Dishman R. Quantifying the placebo effect in psychological 5 outcomes of exercise training: a meta-analysis of randomized trials. Sports Med. 2015;45(5):693–711.

    Article  PubMed  Google Scholar 

  21. Cooney GM, Dwan K, Greig CA, et al. Exercise for depression. Cochrane. 2013;9(CD00436):6.

    Google Scholar 

  22. Ekkekakis P. Honey, I shrunk the pooled SMD! Guide to critical appraisal of systematic reviews and meta-analyses using the Cochrane review on exercise for depression as example. Ment Health Phys Act. 2015;8:21–36.

    Article  Google Scholar 

  23. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283(15):2008–12.

    CAS  Article  PubMed  Google Scholar 

  24. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement. PLoS Clin Trials. 2009;6(7):1–6.

    Google Scholar 

  25. American Psychiatric Association. Diagnostic and statistical manual of mental disorders—DSM-IV-TR. 4th ed. USA: American Psychiatric Association; 2000.

  26. World Health Organisation. The ICD-10 Classification of Mental and Behavioural Disorders – Diagnostic Criteria for Research. 1993.

  27. Hamilton MAX. Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol. 1967;6(4):278–96.

    CAS  Article  PubMed  Google Scholar 

  28. Beck AT, Ward CH, Mendelson M, et al. An inventory for measuring depression. Arch Gen Psych. 1961;4:561–71.

    CAS  Article  Google Scholar 

  29. Silveira H, Moraes H, Oliveira N, et al. Physical exercise and clinically depressed patients: a systematic review and meta-analysis. Neuropsychobiology. 2013;67(2):61–8.

    Article  PubMed  Google Scholar 

  30. Josefsson T, Lindwall M, Archer T. Physical exercise intervention in depressive disorders: meta-analysis and systematic review. Scand J Med Sci Sports. 2014;24(2):259–72.

    CAS  Article  PubMed  Google Scholar 

  31. Higgins JPT, S G. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011. Available from http://www.cochrane-handbook.org. Accessed 3 Jan 2015

  32. Higgins JPT, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.

    CAS  Article  PubMed  Google Scholar 

  34. Egger M, Davey SG, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56(2):455–63.

    CAS  Article  PubMed  Google Scholar 

  36. Rosenthal R. The file drawer problem and tolerance for null results. Psych Bull. 1979;86(3):638–41.

    Article  Google Scholar 

  37. Blumenthal JA, Babyak MA, Doraiswamy PM, et al. Exercise and pharmacotherapy in the treatment of major depressive disorder. Psychosom Med. 2007;69(7):587–96.

  38. Blumenthal JA, Babyak MA, O’Connor C, et al. Effects of exercise training on depressive symptoms in patients with chronic heart failure: the HF-ACTION randomized trial. JAMA. 2012;308(5):465–74.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  39. Bonnet LH. Effects of aerobic exercise in combination with cognitive therapy on self reported depression [dissertation]. Hempstead: Hofstra University; 2005.

    Google Scholar 

  40. Brenes GA, Williamson JD, Messier SP, et al. Treatment of minor depression in older adults: a pilot study comparing sertraline and exercise. Aging Ment Health. 2007;11(1):61–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. Chu I-H, Buckworth J, Kirby TE, et al. Effect of exercise intensity on depressive symptoms in women. Ment Health Phy Act. 2009;2(1):37–43.

    Article  Google Scholar 

  42. Doyne EJ, Ossip-Klein DJ, Bowman ED, et al. Running versus weight lifting in the treatment of depression. J Consult Clin Psychol. 1987;55(5):748.

    CAS  Article  PubMed  Google Scholar 

  43. Dunn AL, Trivedi MH, Kampert JB, et al. Exercise treatment for depression: efficacy and dose response. Am J Prev Med. 2005;28(1):1–8.

    Article  PubMed  Google Scholar 

  44. Epstein D. Aerobic activity versus group cognitive therapy: an evaluative study of contrasting interventions for the alleviation of clinical depression. Reno: University of Nevada; 1986.

    Google Scholar 

  45. Foley LS, Prapavessis H, Osuch EA, et al. An examination of potential mechanisms for exercise as a treatment for depression: a pilot study. Ment Health Phys Act. 2008;1(2):69–73.

    Article  Google Scholar 

  46. Fremont J, Craighead LW. Aerobic exercise and cognitive therapy in the treatment of dysphoric moods. Cogn Ther Res. 1987;11(2):241–51.

    Article  Google Scholar 

  47. Gary RA, Dunbar SB, Higgins MK, et al. Combined exercise and cognitive behavioral therapy improves outcomes in patients with heart failure. J Psychosom Res. 2010;69(2):119–31.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Hemat-Far A, Shahsavari A, Roholla Mousavi S. Effects of selected aerobic exercises on the depression and concentrations of plasma serotonin in the depressed female students aged 18 to 25. J Appl Res Clin Exp Ther. 2012;12(1):47.

    CAS  Google Scholar 

  49. Hess-Homeier MJ. A comparison of Beck’s cognitive therapy and jogging as treatments for depression. Missoula: University of Montana; 1981.

    Google Scholar 

  50. Hoffman JM, Bell KR, Powell JM, et al. A randomized controlled trial of exercise to improve mood after traumatic brain injury. PM R. 2010;2(10):911–9.

  51. Klein MH, Greist JH, Gurman AS, et al. A comparative outcome study of group psychotherapy vs. exercise treatments for depression. Int J Ment Health. 1984:148–76.

  52. Knubben K, Reischies FM, Adli M, et al. A randomised, controlled study on the effects of a short-term endurance training programme in patients with major depression. Br J Sports Med. 2007;41(1):29–33.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. Krogh J, Saltin B, Gluud C, et al. The DEMO trial: a randomized, parallel-group, observer-blinded clinical trial of strength versus aerobic versus relaxation training for patients with mild to moderate depression. J Clin Psychiatry. 2009;70(6):790–800.

    Article  PubMed  Google Scholar 

  54. Mather AS, Rodriguez C, Guthrie MF, et al. Effects of exercise on depressive symptoms in older adults with poorly responsive depressive disorder Randomised controlled trial. Br J Psychiatry. 2002;180(5):411–5.

    Article  PubMed  Google Scholar 

  55. McNeil JK, LeBlanc EM, Joyner M. The effect of exercise on depressive symptoms in the moderately depressed elderly. Psychol Aging. 1991;6(3):487.

    CAS  Article  PubMed  Google Scholar 

  56. Mota-Pereira J, Silverio J, Carvalho S, et al. Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder. J Psychiatr Res. 2011;45(8):1005–11.

    Article  PubMed  Google Scholar 

  57. Mutrie N. Exercise as a treatment for depression within a national health service. Eugene: Microform Publications, College of Human Development and Performance, University of Oregon; 1989.

    Google Scholar 

  58. Nabkasorn C, Miyai N, Sootmongkol A, et al. Effects of physical exercise on depression, neuroendocrine stress hormones and physiological fitness in adolescent females with depressive symptoms. Eur J Public Health. 2006;16(2):179–84.

    Article  PubMed  Google Scholar 

  59. Orth DK. Clinical Treatments for Depression. Morgantown: West Virginia University; 1979.

    Google Scholar 

  60. Setaro JL. Aerobic exercise and group counseling in the treatment of anxiety and depression. Ann Arbor: University Microfilms International/UMI; 1985.

  61. Shahidi M, Mojtahed A, Modabbernia A, et al. Laughter yoga versus group exercise program in elderly depressed women: a randomized controlled trial. Int J Geriatr Psychiatry. 2011;26(3):322–7.

    Article  PubMed  Google Scholar 

  62. Sims J, Galea M, Taylor N, et al. Regenerate: assessing the feasibility of a strength-training program to enhance the physical and mental health of chronic post stroke patients with depression. Int J Geriatr Psychiatry. 2009;24(1):76–83.

    CAS  Article  PubMed  Google Scholar 

  63. Singh NA, Stavrinos TM, Scarbek Y. A randomized controlled trial of high versus low intensity weight training versus general practitioner care for clinical depression in older adults. J Gerontol Biol Sci Med Sci. 2005;60(6):768–76.

    Article  Google Scholar 

  64. Singh NA, Clements KM, Fiatarone MA. A randomized controlled trial of progressive resistance training in depressed elders. J Gerontol Biol Sci Med Sci. 1997;52(1):M27–35.

    CAS  Article  Google Scholar 

  65. Veale D, Le Fevre K, Pantelis C, et al. Aerobic exercise in the adjunctive treatment of depression: a randomized controlled trial. J R Soc Med. 1992;85(9):541–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Williams C, Tappen R. Exercise training for depressed older adults with Alzheimer’s disease. Aging Ment Health. 2008;12(1):72–80.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  67. Danielsson L, Papoulias I, Petersson EL, et al. Exercise or basic body awareness therapy as add-on treatment for major depression: a controlled study. J Affect Disord. 2014;168:98–106.

    Article  PubMed  Google Scholar 

  68. Kerling A, Tegtbur U, Gützlaff E, et al. Effects of adjunctive exercise on physiological and psychological parameters in depression: a randomized pilot trial. J Affect Disord. 2015;177:1–6.

    Article  PubMed  Google Scholar 

  69. Martiny K, Refsgaard E, Lund V, et al. A 9-week randomized trial comparing a chronotherapeutic intervention (wake and light therapy) to exercise in major depressive disorder patients treated with duloxetine. J Clin Psychiatry. 2012;73(9):1234.

    CAS  Article  PubMed  Google Scholar 

  70. Verrusio W, Andreozzi P, Marigliano B, et al. Exercise training and music therapy in elderly with depressive syndrome: a pilot study. Complement Ther Med. 2014;22(4):614–20.

    CAS  Article  PubMed  Google Scholar 

  71. Huang T-T, Liu C-B, Tsai Y-H, et al. Physical fitness exercise versus cognitive behavior therapy on reducing the depressive symptoms among community-dwelling elderly adults: a randomized controlled trial. Int J Nurs Stud. 2015;52(10):1542–52.

    Article  PubMed  Google Scholar 

  72. Salehi I, Hosseini SM, Haghighi M, et al. Electroconvulsive therapy and aerobic exercise training increased BDNF and ameliorated depressive symptoms in patients suffering from treatment-resistant major depressive disorder. J Psychiatr Res. 2014;57:117–24.

  73. Hallgren M, Kraepelien M, Öjehagen A, et al. Physical exercise and internet-based cognitive behavioural therapy in the treatment of depression: randomised controlled trial. Br J Psychiatry. 2015. doi: 10.1192/bjp.bp.114.160101

  74. Belvederi Murri M, Amore M, Menchetti M, et al. Physical exercise for late-life major depression. Br J Psychiatry. 2015;207(3):235–42.

  75. Pilu A, Sorba M, Hardoy MC, et al. Efficacy of physical activity in the adjunctive treatment of major depressive disorders: preliminary results. Clin Pract Epidemiol Ment Health. 2007;3:8.

    Article  PubMed  PubMed Central  Google Scholar 

  76. National Institute for Health and Care Excellence. Depression: management of depression in primary and secondary care. National Institute for Health and Care Excellence: London; 2004.

    Google Scholar 

  77. Nelson ME, Rejeski WJ, Blair SN, et al. Physical activity and public health in older adults: Recommendation from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc. 2007;39(8):1435–45.

    Article  PubMed  Google Scholar 

  78. Blair SN. Physical inactivity: the biggest public health problem of the 21st century. Br J Sports Med. 2009;43(1):1–2.

    PubMed  Google Scholar 

  79. Bridge JA, Birmaher B, Iyengar S, et al. Placebo response in randomized controlled trials of antidepressants for pediatric major depressive disorder. Am J Psychiatry. 2009;166(1):42–9.

    Article  PubMed  Google Scholar 

  80. Stetler C. Adherence, expectations and the placebo response: Why is good adherence to an inert treatment beneficial? Psychol Health. 2014;29(2):127–40.

    Article  PubMed  Google Scholar 

  81. Benedetti F. Placebo effects: understanding the mechanisms in health and disease. New York: Oxford University Press; 2009.

    Google Scholar 

  82. Ojanen M. Can the true effects of exercise on psychological variables be separated from placebo effects?/Les effets veritables de l’exercice physique sur les variables psychologiques peuvent-ils etre separes des effets placebo ? Int J Sport Psychol. 1994;25(1):63–80.

    Google Scholar 

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Author information

Affiliations

  1. Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London, SE5 8AZ, UK

    Brendon Stubbs

  2. Health Service and Population Research Department, Institute of Psychiatry, King’s College London, De Crespigny Park, Box SE5 8AF, London, UK

    Brendon Stubbs

  3. Department of Rehabilitation Sciences, KU Leuven-University of Leuven, Leuven, Belgium

    Davy Vancampfort

  4. KU Leuven-University of Leuven, Z.org Leuven, campus Kortenberg, Kortenberg, Belgium

    Davy Vancampfort

  5. School of Psychiatry, University of New South Wales, Sydney, NSW, Australia

    Simon Rosenbaum & Philip B. Ward

  6. School of Public Health, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia

    Justin Richards

  7. Population Health Research Institute, St. George’s University of London, London, UK

    Michael Ussher

  8. Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil

    Felipe B. Schuch

  9. Graduate Program in Medical Sciences-Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Felipe B. Schuch

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  1. Brendon Stubbs
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  2. Davy Vancampfort
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  3. Simon Rosenbaum
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  4. Philip B. Ward
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  5. Justin Richards
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  6. Michael Ussher
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  7. Felipe B. Schuch
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Corresponding author

Correspondence to Brendon Stubbs.

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Funding

Davy Vancampfort has support from the Research Foundation—Flanders (FWO-Vlaanderen). Brendon Stubbs was supported by the Collaboration for Leadership in Applied Health Research and Care South London theme for this article. No other sources of funding were used to assist in the preparation of this article.

Conflicts of interest

Brendon Stubbs, Davy Vancampfort, Simon Rosenbaum, Philip Ward, Justin Richards, Michael Ussher and Felipe Schuch declare that they have no conflicts of interest relevant to the content of this review.

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Ethical approval was not required to conduct this review.

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Stubbs, B., Vancampfort, D., Rosenbaum, S. et al. Challenges Establishing the Efficacy of Exercise as an Antidepressant Treatment: A Systematic Review and Meta-Analysis of Control Group Responses in Exercise Randomised Controlled Trials. Sports Med 46, 699–713 (2016). https://doi.org/10.1007/s40279-015-0441-5

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Keywords

  • Depressive Symptom
  • Major Depressive Disorder
  • Major Depressive Disorder
  • Standardise Mean Difference
  • Placebo Response