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Exercise as an add-on strategy for the treatment of major depressive disorder: a systematic review

Published online by Cambridge University Press:  03 March 2014

Gioia Mura ,
Maria Francesca Moro ,
Scott B. Patten  and
Mauro G. Carta
Gioia Mura*
Affiliation:
Department of Public Health, Molecular and Clinical Medicine, University of Cagliari, Cagliari, Italy
Maria Francesca Moro
Affiliation:
Department of Public Health, Molecular and Clinical Medicine, University of Cagliari, Cagliari, Italy
Scott B. Patten
Affiliation:
Departments of Community Health Science and Psychiatry, University of Calgary, Calgary, Alberta, Canada
Mauro G. Carta
Affiliation:
Department of Public Health, Molecular and Clinical Medicine, University of Cagliari, Cagliari, Italy
*
Address for correspondence: Dott.ssa Gioia Mura, Centro di Psichiatria di Consultazione e Psicosomatica AOU Cagliari, Via G. Porcell 4, 09100 Cagliari, Italy. (Email: mura.gioia@virgilio.it)
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Abstract

Antidepressants are currently the treatment of choice for major depressive disorder (MDD). Nevertheless, a high percentage of patients do not respond to a first-line antidepressant drug, and combination treatments and augmentation strategies increase the risk of side effects. Moreover, a significant proportion of patients are treatment-resistant. In the last 30 years, a number of studies have sought to establish whether exercise could be regarded as an alternative to antidepressants, but so far no specific analysis has examined the efficacy of exercise as an adjunctive treatment in combination with antidepressants. We carried out a systematic review to evaluate the effectiveness of exercise as an adjunctive treatment with antidepressants on depression.

A search of relevant papers was carried out in PubMed/Medline, Google Scholar, and Scopus with the following keywords: “exercise,” “physical activity,” “physical fitness,” “depressive disorder,” “depression,” “depressive symptoms,” “add-on,” “augmentation,” “adjunction,” and “combined therapy.” Twenty-two full-text articles were retrieved by the search. Among the 13 papers that fulfilled our inclusion criteria, we found methodological weaknesses in the majority. However, the included studies showed a strong effectiveness of exercise combined with antidepressants.

Further analyses and higher quality studies are needed; nevertheless, as we have focused on a particular intervention (exercise in adjunction to antidepressants) that better reflects clinical practice, we can hypothesize that this strategy could be appropriately and safely translated into real-world practice.

Keywords

Adjunction therapyAntidepressantsdepressiondepressive disorderexercisephysical activity

Information

Type
Review Articles
Information
CNS Spectrums , Volume 19 , Issue 6 , December 2014 , pp. 496 - 508
Copyright
Copyright © Cambridge University Press 2013 

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References

1.Murray, CJ, Vos, T, Lozano, R, etal. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380(9859): 2197–2223.Google Scholar
2.Mathers, CD, Loncar, D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006; 3(11): 2011–2030.Google Scholar
3.Hollon, SD, Thase, ME, Markowitz, JC. Treatment and prevention of depression. Psychol Sci Public Interest. 2002; 3(2): 39–77.Google Scholar
4.Gasquet, I, Nègre-Pagès, L, Fourrier, A, etal. Psychotropic drug use and mental psychiatric disorders in France; results of the general population ESEMeD/MHEDEA 2000 epidemiological study. Encephale. 2005; 31(2): 195–206.Google Scholar
5.Carta, MG, Aguglia, E, Bocchetta, A, etal. The use of antidepressant drugs and the lifetime prevalence of major depressive disorders in Italy. Clin Pract Epidemiol Ment Health. 2010; 6: 94–100.Google Scholar
6.Hamer, M, Batty, GD, Seldenrijk, A, Kivimaki, M. Antidepressant medication use and future risk of cardiovascular disease: the Scottish Health Survey. Eur Heart J. 2011; 32(4): 437–442.Google Scholar
7.Olfson, M, Marcus, SC. National patterns in antidepressant medication treatment. Arch Gen Psychiatry. 2009; 66(8): 848–856.Google Scholar
8.Gartlehner, G, Hansen, RA, Thieda, P , etal. Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. Comparative Effectiveness Reviews, No. 7. AHRQ Publication No. 07-EHC007-EF. Rockville, MD: Agency for Healthcare Research and Quality; 2007. http://www.ncbi.nlm.nih.gov/books/NBK43023/.Google Scholar
9.Trivedi, MH, Rush, AJ, Wisniewski, SR, etal. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006; 163: 28–40.Google Scholar
10.Rush, AJ, Trivedi, MH, Wisniewski, SR, etal. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006; 163(11): 1905–1917.CrossRefGoogle ScholarPubMed
11.Thase, M, Howland, R, Friedman, E. Treating antidepressant nonresponders with augmentation strategies: an overview. J Clin Psychiatry. 1998; 59(Suppl 5): 5–12.Google Scholar
12.Treatment-resistant depression: no panacea, many uncertainties. Adverse effects are a major factor in treatment choice. Prescrire Int. 2011; 20: 128–133. [No authors listed].Google Scholar
13.Al-Harbi, KS. Treatment-resistant depression: therapeutic trends, challenges and future directions. Patient Prefer Adherence. 2012; 6: 369–388.Google Scholar
14.Blumenthal, JA, Emery, CF, Madden, DJ, etal. Cardiovascular and behavioral effects of aerobic exercise training in healthy older men and women. J Gerontol. 1989; 44: M147–157.Google Scholar
15.DiLorenzo, TM, Bargman, EP, Stucky-Ropp, R, etal. Long-term effects of aerobic exercise on psychological outcomes. Prev Med. 1999; 28(1): 75–85.Google Scholar
16.Roth, DL, Holmes, DS. Influence of aerobic exercise training and relaxation training on physical and psychologic health following stressful life events. Psychosom Med. 1987; 49: 355–365.Google Scholar
17.King, AC, Taylor, CB, Haskell, WL. Effects of differing intensities and formats of 12 months of exercise training on psychological outcomes in older adults. Health Psychol. 1993; 12(4): 292–300.Google Scholar
18.Klein, MH, Greist, JH, Gurman, AS, Neiberyer, DP. A comparative outcome study of group psychotherapy vs. exercise treatments for depression. International Journal of Mental Health. 1985; 13(3–4): 148–177.Google Scholar
19.Dunn, AL, Trivedi, MH, Kempert, JB, Clark, CG, Chambliss, OH. Exercise treatment for depression: efficacy and dose response. Am J Prev Med. 2005; 28(1): 1–8.Google Scholar
20.Singh, NA, Stavrinos, TM, Scarbek, Y, etal. A randomized controlled trial of high versus low intensity weight training versus general practitioner care for clinical depression in older adults. J Gerontol A Biol Sci Med Sci. 2005; 60(6): 768–776.Google Scholar
21.McNeil, JK, LeBlanc, EM, Joyner, M. The effect of exercise on depressive symptoms in the moderately depressed elderly. Psychol Aging. 1991; 6(3): 487–488.Google Scholar
22.Singh, NA, Clements, KM, Singh, MA. The efficacy of exercise as a long-term antidepressant in elderly subjects: a randomized, controlled trial. J Gerontol A Biol Sci Med Sci. 2001; 56(8): M497–504.Google Scholar
23.Goodwin, VA, Richards, SH, Taylor, RS, Taylor, AH, Campbell, JL. The effectiveness of exercise interventions for people with Parkinson's disease: a systematic review and meta-analysis. Mov Disord. 2008; 23(5): 631–640.Google Scholar
24.Williams, CL, Tappen, RM. Exercise training for depressed older adults with Alzheimer's disease. Aging Ment Health. 2008; 12(1): 72–80.Google Scholar
25.Motl, RW, Pilutti, LA. The benefits of exercise training in multiple sclerosis. Nat Rev Neurol. 2012; 8(9): 487–497.Google Scholar
26.Ades, PA, Coello, CE. Effects of exercise and cardiac rehabilitation on cardiovascular outcomes. Med Clin North Am. 2000; 84(1): 251–265; x–xi.Google Scholar
27.Newton, RU, Galvão, DA. Exercise in prevention and management of cancer. Curr Treat Options Oncol. 2008; 9(2–3): 135–146.Google Scholar
28.Pedersen, BK, Saltin, B. Evidence for prescribing exercise as therapy in chronic disease. Scand J Med Sci Sports. 2006; 16(Suppl 1): 3–63.Google Scholar
29.Kennedy, SH, Eisfeld, BS, Cooke, RG. Quality of life: an important dimension in assessing the treatment of depression? J Psychiatry Neurosci. 2001; 26 Suppl: S23–S28.Google Scholar
30.Carta, MG, Hardoy, MC, Pilu, A, etal. Improving physical quality of life with group physical activity in the adjunctive treatment of major depressive disorder. Clin Pract Epidemiol Ment Health. 2008; 4: 1–14.Google Scholar
31.Blake, H. Physical activity and exercise in the treatment of depression. Front Psychiatry. 2012; 3: 106.Google Scholar
32.Patten, SB, Williams, JV, Lavorato, DH, Bulloch, AG. Recreational physical activity ameliorates some of the negative impact of major depression on health-related quality of life. Front Psychiatry. 2013; 4: 22.Google Scholar
33.Martin, CK, Church, TS, Thompson, AM, Earnest, CP, Blair, SN. Exercise dose and quality of life: a randomized controlled trial. Arch Intern Med. 2009; 169(3): 269–278.Google Scholar
34.Helmich, I, Latini, A, Sigwalt, A, etal. Neurobiological alterations induced by exercise and their impact on depressive disorders. Clin Pract Epidemiol Ment Health. 2010; 6: 115–125.Google Scholar
35.Searle, A, Calnan, M, Lewis, G, etal. Patients’ views of physical activity as treatment for depression: a qualitative study. Br J Gen Pract. 2011; 61(585): 149–156.Google Scholar
36.Lopresti, AL, Hood, SD, Drummond, PD. A review of lifestyle factors that contribute to important pathways associated with major depression: diet, sleep and exercise. J Affect Disord. 2013; 148(1): 12–27.Google Scholar
37.Blake, H, Mo, P, Malik, S, Thomas, S. How effective are physical activity interventions for alleviating depressive symptoms in older people? A systematic review. Clin Rehabil. 2009; 23(10): 873–887.Google Scholar
38.Bridle, C, Spanjers, K, Patel, S, Atherton, NM, Lamb, SE. Effect of exercise on depression severity in older people: systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry. 2012; 201(3): 180–185.CrossRefGoogle ScholarPubMed
39.Brosse, AL, Sheets, ES, Lett, HS, Blumenthal, JA. Exercise and the treatment of clinical depression in adults: recent findings and future directions. Sports Med. 2002; 32(12): 741–760.CrossRefGoogle ScholarPubMed
40.Conn, VS. Depressive symptom outcomes of physical activity interventions: meta-analysis findings. Ann Behav Med. 2010; 39(2): 128–138.Google Scholar
41.Craft, LL, Perna, FM. The benefits of exercise for the clinically depressed. Prim Care Companion J Clin Psychiatry. 2004; 6(3): 104–111.Google Scholar
42.Daley, A. Exercise and depression: a review of reviews. J Clin Psychol Med Settings. 2008; 15(2): 140–147.Google Scholar
43.Gill, A, Womack, R, Safranek, S. Clinical inquiries: does exercise alleviate symptoms of depression? J Fam Pract. 2010; 59(9): 530–531.Google Scholar
44.Greer, TL, Trivedi, MH. Exercise in the treatment of depression. Curr Psychiatry Rep. 2009; 11(6): 466–472.Google Scholar
45.Krogh, J, Nordentoft, M, Sterne, JA, Lawlor, DA. The effect of exercise in clinically depressed adults: systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry. 2011; 72(4): 529–538.Google Scholar
46.Lawlor, D, Hopker, SW. The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled trials. BMJ. 2001; 322(7289): 763–767.Google Scholar
47.Mead, GE, Morley, W, Campbell, P, etal. Exercise for depression. Cochrane Database Syst Rev. 2009;(3): CD004366.Google Scholar
48.Perraton, LG, Kumar, S, Machotka, Z. Exercise parameters in the treatment of clinical depression: a systematic review of randomized controlled trials. J Eval Clin Pract. 2010; 16(3): 597–604.Google Scholar
49.Rethorst, CD, Wipfli, BM, Landers, DM. The antidepressive effects of exercise: a meta-analysis of randomized trials. Sports Med. 2009; 39(6): 491–511.Google Scholar
50.Rimer, J, Dwan, K, Lawlor, DA, etal. Exercise for depression. Cochrane Database Syst Rev. 2012;(7): CD004366.Google Scholar
51.Mura, G, Carta, MG. Physical activity in depressed elderly: a systematic review. Clin Pract Epidemiol Ment Health. 2013; 9: 125–135.Google Scholar
52.Blumenthal, JA, Babyak, MA, Moore, KA, etal. Effects of exercise training on older patients with major depression. Arch Intern Med. 1999; 159: 2349–2356.Google Scholar
53.Knubben, K, Reischies, FM, Adli, M, etal. 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.Google Scholar
54.Martinsen, EW, Medhus, A, Sandvik, L. Effects of aerobic exercise on depression: a controlled study. BMJ. 1985; 291(6488): 109.Google Scholar
55.Martiny, K, Refsgaard, E, Lund, V, etal. 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): 1234–1242.Google Scholar
56.Mather, AS, Rodriguez, C, Guthrie, MF, etal. Effects of exercise on depressive symptoms in older adults with poorly responsive depressive disorder: randomised controlled trial. Br J Psychiatry. 2002; 180: 411–415.CrossRefGoogle ScholarPubMed
57.Matthews, MM, Hsu, FC, Walkup, MP, etal. Depressive symptoms and physical performance in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study. J Am Geriatr Soc. 2011; 59(3): 495–500.Google Scholar
58.Mota-Pereira, J, Silverio, J, Carvalho, S, etal. Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder. J Psychiatr Res. 2011; 45(8): 1005–1011.Google Scholar
59.Pilu, A, Sorba, M, Hardoy, MC, etal. Efficacy of physical activity in the adjunctive treatment of major depressive disorders: preliminary results. Clin Pract Epidem Ment Health. 2007; 3: 8.Google Scholar
60.Rashidi, Z, Rashidi, A, Rouzbahani, R, Rezaei, F. Effects of group exercise on women's depressive symptoms. Journal of Isfahan Medical School. 2013; 30(212): 1861–1865. [In Persian].Google Scholar
61.Schuch, FB, Vasconcelos-Moreno, MP, Borowsky, C, Fleck, MP. Exercise and severe depression: preliminary results of an add-on study. J Affect Disord. 2011; 133(3): 615–618.Google Scholar
62.Veale, D, Le Fevre, K, Pantelis, C, etal. Aerobic exercise in the adjunctive treatment of depression: a randomized controlled trial. J R Soc Med. 1992; 85(9): 541–544.Google Scholar
63.de la Cerda, P, Cervelló, E, Cocca, A, Viciana, J. Effect of an aerobic training program as complementary therapy in patients with moderate depression. Percept Mot Skills. 2011; 112(3): 761–769.Google Scholar
64.Deslandes, AC, Moraes, H, Alves, H, etal. Effect of aerobic training on EEG alpha asymmetry and depressive symptoms in the elderly: a 1-year follow-up study. Braz J Med Biol Res. 2010; 43(6): 585–592.Google Scholar
65.Mota-Pereira, J, Carvalho, S, Silverio, J, etal. Moderate physical exercise and quality of life in patients with treatment-resistant major depressive disorder. J Psychiatr Res. 2011; 45(12): 1657–1659.Google Scholar
66.Brenes, GA, Williamson, JD, Messier, SP, etal. Treatment of minor depression in older adults: a pilot study comparing sertraline and exercise. Aging Ment Health. 2007; 11(1): 61–68.Google Scholar
67.Singh, NA, Clements, KM, Fiatarone, MA. A randomized controlled trial of progressive resistance training in depressed elders. J Gerontol A Biol Sci Med Sci. 1997; 52(1): M27–35.Google Scholar
68.Rush, AJ, Golden, WE, Hall, GW, etalDepression in Primary Care, Vol. 1: Detection and Diagnosis. Clinical Practice Guideline, Number 5. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research; 1993.Google Scholar
69.Rush, AJ, Golden, WE, Hall, GW, etal. Depression in Primary Care, Vol. 2: Treatment of Major Depression. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research; 1993.Google Scholar
70.Callaghan, P, Khalil, E, Morres, I, Carter, I. Pragmatic randomised controlled trial of preferred intensity exercise in women living with depression. BMC Public Health. 2011; 11: 465.Google Scholar
71.Rutherford, BR, Mori, S, Sneed, JR, Pimontel, MA, Roose, SP. Contribution of spontaneous improvement to placebo response in depression: a meta-analytic review. J Psychiatr Res. 2012; 46(6): 697–702.Google Scholar
72.Iovieno, N, Papakostas, GI. Correlation between different levels of placebo response rate and clinical trial outcome in major depressive disorder: a meta-analysis. J Clin Psychiatry. 2012; 73(10): 1300–1306.Google Scholar
73.Mota-Pereira, J, Silverio, J, Carvalho, S, Ramos, J, Ribeiro, JC. Physical exercise and major depressive disorder—where do we stand? Curr Psychopharmacol. 2012; 1(2): 167–177.CrossRefGoogle Scholar
74.Chalder, M, Wiles, NJ, Campbell, J, etal. Facilitated physical activity as a treatment for depressed adults: randomised controlled trial. BMJ. 2012; 344: e2758.Google Scholar
75.Neto, FL, Borges, G, Torres-Sanchez, S, Mico, JA, Berrocoso, E. Neurotrophins role in depression neurobiology: a review of basic and clinical evidence. Curr Neuropharmacol. 2011; 9(4): 530–552.Google Scholar
76.Mendez-David, I, Hen, R, Gardier, AM, David, DJ. Adult hippocampal neurogenesis: an actor in the antidepressant-like action. Ann Pharm Fr. 2013; 71(3): 143–149.Google Scholar
77.Tanti, A, Belzung, C. Hippocampal neurogenesis: a biomarker for depression or antidepressant effects? Methodological considerations and perspectives for future research. Cell Tissue Res. 2013; 354(1): 203–219.Google Scholar
78.De Foubert, G, Carney, SL, Robinson, CS, etal. Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment. Neuroscience. 2004; 128(3): 597–604.Google Scholar
79.Coppell, AL, Pei, Q, Zetterstrom, TS. Bi-phasic change in BDNF gene expression following antidepressant drug treatment. Neuropharmacology. 2003; 44(7): 903–910.Google Scholar
80.Russo-Neustadt, AA, Alejandre, H, Garcia, C, Ivy, AS, Chen, MJ. Hippocampal brain-derived neurotrophic factor expression following treatment with reboxetine, citalopram, and physical exercise. Neuropsychopharmacology. 2004; 29(12): 2189–2199.Google Scholar
81.Czubak, A, Nowakowska, E, Kus, K, etal. Influences of chronic venlafaxine, olanzapine and nicotine on the hippocampal and cortical concentrations of brain-derived neurotrophic factor (BDNF). Pharmacol Rep. 2009; 61(6): 1017–1023.Google Scholar
82.Nibuya, M, Morinobu, S, Duman, RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci. 1995; 15(11): 7539–7547.Google Scholar
83.Altar, CA, Whitehead, RE, Chen, R, Wortwein, G, Madsen, TM. Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain. Biol Psychiatry. 2003; 54(7): 703–709.Google Scholar
84.Neeper, SA, Gomez-Pinilla, F, Choi, J, Cotman, CW. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 1996; 726(1–2): 49–56.Google Scholar
85.Russo-Neustadt, A, Beard, RC, Cotman, CW. Exercise, anti-depressant medications, and enhanced brain derived neurotrophic factor expression. Neuropsychopharmacology. 1999; 21(5): 679–682.Google Scholar
86.Adlard, PA, Perreau, VM, Engesser-Cesar, C, Cotman, CW. The timecourse of induction of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus following voluntary exercise. Neurosci Lett. 2004; 363(1): 43–48.Google Scholar
87.Arunrut, T, Alejandre, H, Chen, M, Cha, J, Russo-Neustadt, A. Differential behavioral and neurochemical effects of exercise, reboxetine and citalopram with the forced swim test. Life Sci. 2009; 84(17–18): 584–589.Google Scholar
88.Russo-Neustadt, A, Ha, T, Ramirez, R, Kesslak, JP. Physical activity-antidepressant treatment combination: impact on brain-derived neurotrophic factor and behavior in an animal model. Behav Brain Res. 2001; 120(1): 87–95.Google Scholar
89.Garza, AA, Ha, TG, Garcia, C, Chen, MJ, Russo-Neustadt, AA. Exercise, antidepressant treatment, and BDNF mRNA expression in the aging brain. Pharmacol Biochem Behav. 2004; 77(2): 209–220.Google Scholar
90.Branchi, I, Santarelli, S, Capoccia, S, etal. Antidepressant treatment outcome depends on the quality of the living environment: a pre-clinical investigation in mice. PLoS One. 2013; 8(4): e62226.Google Scholar
91.Josefsson, T, Lindwall, M, Archer, T. Physical exercise intervention in depressive disorders: meta-analysis and systematic review. Scand J Med Sci Sports. In press. DOI: 10.1111/sms.12050.Google Scholar
92.Silveira, H, Moraes, H, Oliveira, N, etal. Physical exercise and clinically depressed patients: a systematic review and meta-analysis. Neuropsychobiology. 2013; 67(2): 61–68.Google Scholar
93.Danielsson, L, Noras, AM, Waern, M, Carlsson, J. Exercise in the treatment of major depression: a systematic review grading the quality of evidence. Physiother Theory Pract. 2013; 29(8): 573–585.Google Scholar
94.Craft, LL, Landers, DM. The effect of exercise on clinical depression and depression resulting from mental illness: a meta-analysis. J Sport Exerc Psychol. 1998; 20(4): 339–357.Google Scholar
95.North, TC, McCullagh, P, Tran, ZV. Effect of exercise on depression. Exerc Sport Sci Rev. 1990; 18: 379–415.Google Scholar