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Review Article |

Effect of Exercise Training on Depressive Symptoms Among Patients With a Chronic Illness:  A Systematic Review and Meta-analysis of Randomized Controlled Trials FREE

Matthew P. Herring, PhD; Timothy W. Puetz, PhD; Patrick J. O’Connor, PhD; Rodney K. Dishman, PhD
[+] Author Affiliations

Author Affiliations: Department of Kinesiology, The University of Georgia, Athens (Drs Herring, Puetz, O’Connor, and Dishman); Department of Epidemiology, University of Alabama at Birmingham (Dr Herring); and Department of Behavioral Science and Health Education, Rollins School of Public Health, Emory University, Atlanta, Georgia (Dr Puetz).


Arch Intern Med. 2012;172(2):101-111. doi:10.1001/archinternmed.2011.696.
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Published online

Background Physical inactivity and comorbid depressive symptoms are prevalent among patients with a chronic illness. To our knowledge, randomized controlled trials of the effects of exercise training on depressive symptoms among patients with a chronic illness have not been systematically reviewed. We estimated the population effect of exercise training on depressive symptoms and determined whether the effect varied according to patient characteristics and modifiable features of exercise exposure and clinical settings.

Methods Articles published before June 1, 2011, were located using the Physical Activity Guidelines for Americans Scientific Database, Google Scholar, MEDLINE, PsycINFO, PubMed, and Web of Science. Ninety articles involving 10 534 sedentary patients with a chronic illness were selected. Included articles required (1) randomized allocation to an exercise intervention or nonexercise comparison condition and (2) a depression outcome assessed at baseline and at mid- and/or postintervention. Hedges d effect sizes were computed, study quality was evaluated, and random effects models were used to estimate sampling error and population variance of the observed effects.

Results Exercise training significantly reduced depressive symptoms by a heterogeneous mean effect size delta (Δ) of 0.30 (95% CI, 0.25-0.36). Larger antidepressant effects were obtained when (1) baseline depressive symptoms were higher, (2) patients met recommended physical activity levels, and (3) the trial primary outcome, predominantly function related, was significantly improved among patients having baseline depressive symptoms indicative of mild-to-moderate depression.

Conclusions Exercise reduces depressive symptoms among patients with a chronic illness. Patients with depressive symptoms indicative of mild-to-moderate depression and for whom exercise training improves function-related outcomes achieve the largest antidepressant effects.

Figures in this Article

Physical inactivity and comorbid depressive disorders are common among patients with a chronic illness and are prevalent public health problems.1 The relationship between depression and chronic illness is bidirectional.2 Depression is associated with increased risk of a chronic illness3 and mortality4; conversely, several chronic illnesses increase the risk of depression.5

The adverse health outcomes associated with comorbid depressive symptoms among chronically ill patients are well established.1 Depressive symptoms are associated with reduced adherence to prescribed medical treatments6 and health-related quality of life,7 as well as increased symptom burden,8 disability,9 functional and role impairment,10 and use of health care services.10,11

Recent evidence has questioned the efficacy of pharmacotherapy for individuals with mildly to moderately elevated depressive symptoms12 and among patients with comorbid chronic illnesses.13 Thus, there continues to be interest in alternative therapies, including somatic treatments, herbal remedies, relaxation, and exercise.14

Although exercise training is associated with improved physical and mental health outcomes, including reduced mortality15 and anxiety symptoms,16 among patients with chronic illness, early trials in those with heart disease reported mixed effects of exercise on depressive symptoms.1719 Methodologic shortcomings of those trials (eg, now outdated outcome measures or insufficient reporting of score distributions) preclude meaningful comparison with effects from contemporary trials. Meta-analytic reviews of exercise effects on depressive symptoms have since focused on patients having a diagnosis of a depressive disorder,2022 adults with or without depression,23 and women with postnatal depression.24 Meta-analytic reviews of patients with cardiovascular disease,25 chronic obstructive pulmonary disease,26 fibromyalgia,27 and Parkinson disease28 also have supported the antidepressant effects of exercise, but they included nonrandomized trials likely influenced by self-selection bias.

We used the results of randomized controlled trials to evaluate the effects of exercise training on depressive symptoms among chronically ill patients who did not have a diagnosis of a depressive disorder. Prior reviews20,22 have faulted exercise trials for small sample sizes, insufficient blinding of participant allocation, inadequate control comparisons, and lack of intent-to-treat analyses. We weighted effects by trial size and included in moderator analysis whether trials used blinded allocation, attention-control comparisons, and intent-to-treat analyses. Our further evaluation of practical variables, including illness type, physical activity exposure, and baseline symptom severity, has the potential to assist clinicians by providing evidence on which to base exercise prescriptions. The objectives of the review reported here were to estimate the population effect of exercise on depressive symptoms and to determine whether the effect varied according to patient characteristics and modifiable features of exercise exposure and clinical settings.

This systematic review and meta-regression analysis was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement guidelines.29

DATA SOURCES AND SEARCHES

Articles published before June 1, 2011, were located using searches of the Physical Activity Guidelines for Americans Scientific Database, Google Scholar, MEDLINE, PsycINFO, PubMed, and Web of Science using combinations of exercisetraining, physical activity, depression, chronic illness, patients, randomizedtrial, and randomized controlled trial. Reference lists from retrieved articles were manually reviewed.

STUDY SELECTION

Inclusion criteria were (1) publications available in English, (2) sedentary adults with a chronic illness, (3) randomized allocation to either exercise training or a nonexercise comparison, and (4) a depression outcome measured at baseline and during and/or after exercise training.

Excluded investigations (1) sampled patients with a clinical diagnosis of depression, (2) included exercise as one part of a multicomponent intervention but did not include the additional component in a comparison condition, (3) compared exercise only with an active treatment (eg, pharmacotherapy or another mode of exercise), (4) used education or promotion interventions aimed at increasing physical activity but failed to show increased physical activity, and/or (5) did not use a screening or clinical measure of depressive symptoms. Figure 1 presents a flowchart of study selection.

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Figure 1. Flowchart of study selection. RCTs indicates randomized controlled trials.

STUDY CHARACTERISTICS

One hundred sixty-eight effects were derived from 90 studies: 39 from patients with a cardiovascular or cardiometabolic disease, 37 from patients with chronic pain other than fibromyalgia (eg, knee osteoarthritis or back pain), 32 from patients with fibromyalgia, 16 from obese patients, 15 from patients with cancer, 8 from patients with neurologic disorders other than multiple sclerosis (eg, spinal cord injury or Alzheimer disease), 6 from patients with chronic obstructive pulmonary disease, 6 from patients with multiple sclerosis, 5 from patients categorized as having “other medical illnesses” (eg, human immunodeficiency virus disease), and 4 from patients with psychological disorders other than depression (see eReferences).

Depressive symptoms were the primary outcome for only 3 studies.3032 Primary outcomes were a variety of objective (eg, body weight, body mass index, fat mass, 6-minute walk, treadmill time, peak power output during cycling, peak oxygen uptake, peak leg torque, and left ventricular ejection fraction) and self-reported (eg, dyspnea, pain, fatigue, physical function, and multidimensional quality of life) function-related measures.

The mean (SD) age was 51 (15) years. The mean percentage of women was 61% (34%). Exercise training consisted of 3 (1) sessions per week, 42 (18) minutes per session, and 17 (13) weeks' duration. The mean exercise training adherence rate was 77% (13%) of prescribed sessions. Adherence was reported for 104 of 168 of the effects (61.9%). The most frequently used depression measures were the Beck Depression Inventory33 (k = 40), the Center for Epidemiological Studies Depression Scale34 (k = 40), and the depression scale of the Hospital Anxiety and Depression Scale35 (k = 27).

DATA EXTRACTION AND QUALITY ASSESSMENT

We independently assessed study quality. A widely used method36 was extended to include assessments of randomization methods, blinding of allocation to treatment, attention-control use, depression measure quality, adherence, intent-to-treat analyses, and exercise program descriptions.

EFFECT SIZE CALCULATION

Effect sizes were calculated by subtracting the mean change in the comparison condition from the mean change in the exercise condition and dividing the difference by the pooled standard deviation of baseline scores.37 Effect sizes were adjusted for small sample size bias and calculated; a larger decrease in depressive symptoms among exercising patients resulted in a positive effect size.37 When exact means and standard deviations were not provided (k = 8), effect sizes were estimated38 from exact F test values with 1 df,39 from exact P values,4044 and from a figure shown in the article reviewed.45,46 When an SD was not reported (k = 1),47 it was estimated from the largest other study48 of the same illness type, using the same depression measure.

DATA SYNTHESIS AND ANALYSIS

Meta-regression was used as the overall analysis of moderator effects to reduce the probability of type I error by computing simultaneous estimates of independent effects by multiple moderator variables on the variation in effect size across trials. With macros (SPSS MeanES, MetaReg; SPSS, Inc), we used random effects models to aggregate mean effect size delta (Δ) and to test variation in effects according to moderator variables.37,49 Heterogeneity was indicated if QTotal reached a significance level of P < .05 and the sampling error accounted for less than 75% of the observed variance.37 Heterogeneity also was assessed by examination of the I2 statistic.50 The number of unpublished or unretrieved studies of null effect that would diminish the significance of observed effects to P > .05 was estimated as fail-safe N.51 Potential publication bias (ie, smaller studies showing larger effects) also was addressed by evaluation of a funnel plot. Two-way (effects × raters) intraclass correlation coefficients for absolute agreement were calculated to examine interrater reliability for depressive symptom effect sizes and moderators. The initial intraclass correlation coefficients, based on 36 effects, were 0.93 or larger. Discrepancies were resolved by adjudication after recalculation and/or recoding.

PRIMARY MODERATORS

To provide focused research hypotheses about variation in effect size,52 baseline depressive symptom scores, as well as 7 primary moderators, were selected a priori on the basis of logical, theoretical, or empirical relations to depression (see eTable 1): physical activity exposure, change in fitness (ie, increased aerobic capacity or muscular strength),53 illness type (categorized as physical or psychosomatic /neurologic),54 trial primary outcome change,55 blinded allocation, attention-control use, and intent-to-treat analysis.

PRIMARY MODERATOR ANALYSIS

Each of the 7 primary moderators was coded according to planned contrasts56 (P ≤ .05) among its levels. Primary moderators and baseline depressive symptom scores were included in mixed-effects multiple linear regression analysis with maximum likelihood estimation,37,49 adjusting both for depression measure and nonindependence of multiple effects contributed by single studies.57 Tests of the regression model (QR) and its residual error (QE) are reported. A follow-up meta-regression model was used to test 2-way interactions among significant primary moderators. A significant interaction between baseline depressive symptoms and the primary trial outcome was decomposed by post hoc contrasts of interaction combinations based on whether baseline depressive symptoms were indicative of mild-to-moderate depression5862 and whether the primary trial outcome was favorable.

SECONDARY MODERATORS AND ANALYSIS

Secondary moderators were selected for descriptive, univariate analyses (see eTable 1). Random effects models were used to calculate mean effect sizes (Δ) and 95% CIs for continuous and categorical variables.49

One hundred forty-five of 168 effects (86.3%) were larger than zero. A forest plot and annotated table of the unweighted distribution of effects are presented in Figure 2 and Table 1. The mean effect size Δ was 0.30 (95% CI, 0.25-0.36; z = 10.51; P < .001). The significant improvement in depressive symptoms after exercise training was moderately heterogeneous (Q167 = 314.81; P < .001; I2 = 47%), with sampling error accounting for 49.5% of the observed variance. A sensitivity analysis revealed similar depressive symptom reductions among trials in which depressive symptoms were (Δ = 0.29; 95% CI, 0.05-0.52; P = .02; k = 13) or were not (Δ = 0.31; 95% CI, 0.25-0.36; P < .001; k = 155) the primary outcome. The fail-safe number of effects was 8173, and examination of a funnel plot also revealed a lack of publication bias (see eFigure 1).

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Figure 2. Forest plot of unweighted distribution of Hedges d effect sizes.

Table Graphic Jump LocationTable 1. Annotated Descriptors of Unweighted Hedges d Effect Sizes
PRIMARY MODERATOR ANALYSES

The overall meta-regression model was significant (QR10 = 43.36; P < .001; R2 = 0.30; QE150 = 99.51; P > .99). Baseline depressive symptom scores (β = 0.26; z = 2.86; P = .004), physical activity exposure (β = 0.25; z = 2.61; P = .01), and primary trial outcome change (β = 0.31; z = 3.32; P < .001) accounted for significant variation in the overall effect of exercise on depressive symptoms. Effects were larger when (1) patients were meeting moderate or vigorous physical activity recommendations (Δ = 0.46; 95% CI, 0.35-0.56) compared with not meeting either recommendation (Δ = 0.24; 95% CI, 0.18-0.31; z = 3.29; P = .001) and (2) the primary trial outcome was significantly improved (Δ = 0.43; 95% CI, 0.34-0.52) compared with no significant change (Δ = 0.22; 95% CI, 0.14-0.29; z = 3.67; P < .001). Fitness change (β = 0.14; z = 1.53; P = .13), illness type (β = 0.09; z = 0.88; P = .09), blinded allocation (β = 0.17; z = 1.66; P = .10), attention-control use (β = −0.09; z = −1.02; P = .31), and whether intent-to-treat analysis was used (β = −0.12; z = 1.36; P = .17) were not related to effect size.

A 2-way interaction was found between baseline depressive symptoms and primary trial outcome change (β = 0.43; z = 2.41; P = .02). All other 2-way interactions were statistically nonsignificant (primary trial outcome by exposure: β = 0.14; P = .22, and baseline depressive symptoms by exposure: β = 0.14; P = .34). At least 1 level of all moderators had sufficient heterogeneity (I2 range, 50%-70%) and number of effects (k = 23-98) to permit a good test of interactions.

Decomposition of the interaction showed significantly larger improvements for investigations in which the primary outcome was significantly improved among patients with baseline depressive symptoms indicative of mild-to-moderate depression (Δ = 0.79; 95% CI, 0.58-1.01) when contrasted with the average effect of other interaction combinations (Δ = 0.27; 95% CI, 0.21-0.33; z = 4.57; P < .001).

SECONDARY MODERATOR ANALYSES

The results of univariate moderator analyses for primary and secondary moderators are presented in Table 2. The number of effects (k), mean effect size Δ, 95% CI, and P value are provided for each level of each moderator variable.

Table Graphic Jump LocationTable 2. Summary of Univariate Moderator Analysis

The cumulative evidence summarized here indicates that exercise training reduces depressive symptoms among chronically ill patients. The magnitude of the overall mean effect is small but comparable to (1) exercise effects on related mental health outcomes among patients, including anxiety,16 fatigue,64 pain,65 and quality of life,66 and (2) the effect of pharmacotherapy on depressive symptoms among patients with stroke67 and fibromyalgia.68 Expressed as a binomial effect,69 the effect of exercise is equivalent to a clinical effect of 7.5% beyond chance for patients exposed to exercise, hypothetically benefiting approximately 790 of the 10 534 patients included in the reviewed trials. Expressed as a function of absolute risk reduction, the lowered depressive symptoms found among exercising patients are equivalent to a number needed to treat70 of approximately 6; depressive symptom reductions could be expected to occur for at least 1 patient for every 6 chronically ill patients experiencing depressive symptoms who would engage in exercise training. Even mild-to-moderate depressive symptoms among chronically ill patients are associated with restrictions in social and recreational activities71 and with lower adherence to lifestyle changes recommended by physicians to reduce future health risks.72 Hence, the evidence reported here should encourage physicians to recommend exercise as a clinically meaningful way to reduce depressive symptoms in several patient populations.

The purpose of our meta-regression was to examine patient characteristics and features of exercise and clinical settings that could be modified to optimize the effect of exercise on depressive symptoms. The purpose was not to test whether those factors might help to explain the effect of exercise. That purpose would require that trials assess plausible mediators of exercise effects, which was rarely the case in the included trials. Depressive symptom reductions were larger in patients with higher symptom scores at baseline regardless of the depression measure used. The review reported herein did not focus on exercise training effects among patients with a diagnosis of a depressive disorder. Nonetheless, 34 of 168 effects (20.2%) came from symptom scores high enough to suggest a clinical elevation. Based on cutoff scores commonly used for clinical screening,5862 larger effects were found among patients with baseline scores indicative of mild-to-moderate depression. Although depression was not diagnosed in the trials reviewed herein, it is likely that patients with clinical depression were included.

The largest depressive symptom reductions were found when the primary trial outcome, predominantly categorized as function related, was improved among patients with elevated baseline depressive symptoms. Most effects (141 of 168) stemmed from studies of function-related primary outcomes, including pain, physical function, and function-related quality of life. This finding is noteworthy given the importance of functional improvements among patients.55,73 Elevated depressive symptoms predict functional decline in older adults,74 and exercise training may improve function by first reducing depressive symptoms. It is also plausible that depressive symptom reductions are explained in part by significant improvements in function-related outcomes among patients. The largest symptom reductions were observed for the 12 of 14 effects for which function-related outcomes were significantly improved among patients with baseline depressive symptoms indicative of mild-to-moderate depression. It also is noteworthy that these 14 effects resulted from investigations of patients with fibromyalgia or cardiovascular disorders, who often are characterized as having increased pain and impaired physical function. For example, a 16-week single-blind, randomized attention-controlled trial of 65 patients with fibromyalgia with baseline Beck Depression Inventory scores indicative of mild-to-moderate depression revealed a large reduction in depressive symptoms (Hedges d = 0.69) and a correspondingly large, statistically significant reduction in symptoms of pain, physical function, and fibromyalgia-related quality of life (Hedges d = 1.04).63

Those findings should be interpreted with caution because only 30 of the 141 function-related effects (21.3%) were derived from investigations of objective, function-related outcomes. Although the method of measuring function-related outcomes (self-report vs objective) was not a significant moderator of effects overall, reductions in depressive symptoms in trials that used a self-report assessment of a function-related outcome were larger when the outcome was significantly improved. This finding suggests that the relation between exercise-induced improvements in function-related outcomes and depressive symptom reductions may have been confounded in some studies by a common method bias of using self-report measures.

Our analysis did not permit a rigorous test of the minimal or optimal effective dose of physical activity, mostly because many trials used a similar prescription consistent with long-standing recommendations for increasing or maintaining fitness.75,76 Nevertheless, using the reported types, intensities, and timing of physical activity, we were able to estimate whether each trial met contemporary physical activity recommendations.77,78 Depressive symptom reductions were significantly larger among patients who met moderate or vigorous physical activity recommendations. This finding provides support for the use of current physical activity recommendations to reduce depressive symptoms among patients. Because it is possible that healthier participants were recruited into the trials that used exercise interventions that were consistent with currently recommended guidelines, optimal dosing of exercise exposure needs experimental confirmation.

Although double-blind allocation is not feasible in exercise interventions, 79 effects were derived from trials that concealed treatment allocation from the staff who conducted depressive symptom assessments. Symptom reductions were similar for trials that reported blinded allocation and trials that did not. Depressive symptom reductions in trials that used a no-treatment comparison did not differ significantly from reductions in trials that used an attention-control comparison. Thus, exercise effects were not solely attributable to attention from researchers. The use of intent-to-treat analysis did not alter effect size alone or independently of other moderators. Exercise adherence was not a significant moderator and was not lower in intent-to-treat trials, but adherence data were reported for more effects in intent-to-treat trials (k = 41 of 53 [77.4%]) than efficacy trials (k = 63 of 115 [54.8%]).

Well-designed randomized controlled trials of exercise effects on depressive symptoms are needed that focus on patients with a chronic illness who have had a depressive disorder diagnosed. Future trials should use objective measures of function to examine the potential mediating effect of function-related improvements in patients with elevated depressive symptoms. Also needed are well-designed investigations that examine the effects of overall exercise training dose in the context of whether patients are meeting recommended levels of physical activity.

Depressive symptom reduction is a favorable adventitious outcome of exercise training interventions designed as treatments for chronic illnesses other than depression. The present findings provide evidence to recommend exercise training to patients as a potential low-risk, adjuvant treatment for depressive symptoms that may develop during chronic illness. The findings also suggest that larger depressive-symptom reductions will be achieved by focusing on the improvement of function-related outcomes among chronically ill patients with mild-to-moderate elevations in depressive symptoms.

Correspondence: Matthew P. Herring, PhD, Department of Epidemiology, University of Alabama at Birmingham, 1530 Third Ave S, Ryals Public Health Bldg, Room 210E, Birmingham, AL 35294 (mattpherring@gmail.com).

Accepted for Publication: September 25, 2011.

Author Contributions: Dr Herring had full access to all the data and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Herring and Dishman. Acquisition of data: Herring, Puetz, and Dishman. Analysis and interpretation of data: Herring, Puetz, O’Connor, and Dishman. Drafting of the manuscript: Herring and Puetz. Critical revision of the manuscript for important intellectual content: Herring, Puetz, O’Connor, and Dishman. Statistical analysis: Herring, Puetz, and Dishman. Administrative, technical, or material support: Herring and Puetz. Supervision: Herring and Dishman.

Financial Disclosure: None reported.

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Etnier JL, Karper WB, Gapin JI, Barella LA, Chang YK, Murphy KJ. Exercise, fibromyalgia, and fibrofog: a pilot study.  J Phys Act Health. 2009;6(2):239-246
PubMed
Flynn KE, Piña IL, Whellan DJ,  et al; HF-ACTION Investigators.  Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial.  JAMA. 2009;301(14):1451-1459
PubMed   |  Link to Article
Penninx BWJH, Rejeski WJ, Pandya J,  et al.  Exercise and depressive symptoms: a comparison of aerobic and resistance exercise effects on emotional and physical function in older persons with high and low depressive symptomatology.  J Gerontol B Psychol Sci Soc Sci. 2002;57(2):P124-P132
PubMed   |  Link to Article
Strömbeck BE, Theander E, Jacobsson LTH. Effects of exercise on aerobic capacity and fatigue in women with primary Sjögren's syndrome.  Rheumatology (Oxford). 2007;46(5):868-871
PubMed   |  Link to Article
Emery CF, Schein RL, Hauck ER, MacIntyre NR. Psychological and cognitive outcomes of a randomized trial of exercise among patients with chronic obstructive pulmonary disease.  Health Psychol. 1998;17(3):232-240
PubMed   |  Link to Article
Skrinar GS, Huxley NA, Hutchinson DS, Menninger E, Glew P. The role of a fitness intervention on people with serious psychiatric disabilities.  Psychiatr Rehabil J. 2005;29(2):122-127
PubMed   |  Link to Article
Leibetseder V, Strauss-Blasche G, Marktl W, Ekmekcioglu C. Does aerobic training enhance effects of spa therapy in back pain patients? a randomized, controlled clinical trial.  Forsch Komplementarmed. 2007;14(4):202-206
PubMed   |  Link to Article
Lim H-J, Moon Y-I, Lee MS. Effects of home-based daily exercise therapy on joint mobility, daily activity, pain, and depression in patients with ankylosing spondylitis.  Rheumatol Int. 2005;25(3):225-229
PubMed   |  Link to Article
Payne JK, Held J, Thorpe J, Shaw H. Effect of exercise on biomarkers, fatigue, sleep disturbances, and depressive symptoms in older women with breast cancer receiving hormonal therapy.  Oncol Nurs Forum. 2008;35(4):635-642
PubMed   |  Link to Article
Courneya KS, Segal RJ, Gelmon K,  et al.  Six-month follow-up of patient-rated outcomes in a randomized controlled trial of exercise training during breast cancer chemotherapy.  Cancer Epidemiol Biomarkers Prev. 2007;16(12):2572-2578
PubMed   |  Link to Article
Lipsey MW, Wilson DB. Practical Meta-analysis. Newbury Park, CA: Sage Publications; 2001
Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses.  BMJ. 2003;327(7414):557-560
PubMed   |  Link to Article
Rosenberg MS. The file-drawer problem revisited: a general weighted method for calculating fail-safe numbers in meta-analysis.  Evolution. 2005;59(2):464-468
PubMed
Rosenthal R, DiMatteo MR. Meta-analysis: recent developments in quantitative methods for literature reviews.  Annu Rev Psychol. 2001;52(1):59-82
PubMed   |  Link to Article
Dunn AL, Trivedi MH, O’Neal HA. Physical activity dose-response effects on outcomes of depression and anxiety.  Med Sci Sports Exerc. 2001;33(6):(suppl)  S587-S597, discussion 609-610
PubMed
Booth FW, Chakravarthy MV, Gordon SE, Spangenburg EE. Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy.  J Appl Physiol. 2002;93(1):3-30
PubMed
Stewart AL, Hays RD, Wells KB, Rogers WH, Spritzer KL, Greenfield S. Long-term functioning and well-being outcomes associated with physical activity and exercise in patients with chronic conditions in the Medical Outcomes Study.  J Clin Epidemiol. 1994;47(7):719-730
PubMed   |  Link to Article
Rosenthal R. Meta-analytic Procedures for Social Research. London, England: Sage Publications; 1991
Gleser LJ, Olkin I. Stochastically dependent effect sizes. In: Cooper H, Hedges LV, eds. The Handbook of Research Synthesis. New York, NY: Russell Sage Foundation; 1994:339-355
Kendall PC, Hollon SD, Beck AT, Hammen CL, Ingram RE. Issues and recommendations regarding use of the Beck Depression Inventory.  Cognit Ther Res. 1987;11(3):289-299Link to Article
Link to Article
Weissman MM, Sholomskas D, Pottenger M, Prusoff BA, Locke BZ. Assessing depressive symptoms in five psychiatric populations: a validation study.  Am J Epidemiol. 1977;106(3):203-214
PubMed
Crawford JR, Henry JD, Crombie C, Taylor EP. Normative data for the HADS from a large non-clinical sample.  Br J Clin Psychol. 2001;40(pt 4):429-434
PubMed   |  Link to Article
Rush AJ, Bernstein IH, Trivedi MH,  et al.  An evaluation of the Quick Inventory of Depressive Symptomatology and the Hamilton Rating Scale for Depression: a sequenced treatment alternative to relieve depression trial report.  Biol Psychiatry. 2006;59(6):493-501
PubMed   |  Link to Article
Yesavage JA, Brink TL, Rose TL,  et al.  Development and validation of a geriatric depression screening scale: a preliminary report.  J Psychiatr Res. 1982-1983;17(1):37-49
PubMed   |  Link to Article
Rooks DS, Gautam S, Romeling M,  et al.  Group exercise, education, and combination self-management in women with fibromyalgia: a randomized trial.  Arch Intern Med. 2007;167(20):2192-2200
PubMed   |  Link to Article
Puetz TW, O’Connor PJ, Dishman RK. Effects of chronic exercise on feelings of energy and fatigue: a quantitative synthesis.  Psychol Bull. 2006;132(6):866-876
PubMed   |  Link to Article
Hernández-Molina G, Reichenbach S, Zhang B, Lavalley M, Felson DT. Effect of therapeutic exercise for hip osteoarthritis pain: results of a meta-analysis.  Arthritis Rheum. 2008;59(9):1221-1228
PubMed   |  Link to Article
van Tol BAF, Huijsmans RJ, Kroon DW, Schothorst M, Kwakkel G. Effects of exercise training on cardiac performance, exercise capacity and quality of life in patients with heart failure: a meta-analysis.  Eur J Heart Fail. 2006;8(8):841-850
PubMed   |  Link to Article
Chen Y, Guo JJ, Zhan S, Patel NC. Treatment effects of antidepressants in patients with post-stroke depression: a meta-analysis.  Ann Pharmacother. 2006;40(12):2115-2122
PubMed   |  Link to Article
Häuser W, Bernardy K, Uçeyler N, Sommer C. Treatment of fibromyalgia syndrome with antidepressants: a meta-analysis.  JAMA. 2009;301(2):198-209
PubMed   |  Link to Article
Rosenthal R, Rubin DB. A simple, general purpose display of magnitude of experimental effect.  J Educ Psychol. 1982;74(2):166-169Link to Article
Link to Article
Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect.  BMJ. 1995;310(6977):452-454
PubMed   |  Link to Article
Mausbach BT, Chattillion EA, Moore RC, Roepke SK, Depp CA, Roesch S. Activity restriction and depression in medical patients and their caregivers: a meta-analysis.  Clin Psychol Rev. 2011;31(6):900-908
PubMed   |  Link to Article
Ziegelstein RC, Fauerbach JA, Stevens SS, Romanelli J, Richter DP, Bush DE. Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction.  Arch Intern Med. 2000;160(12):1818-1823
PubMed   |  Link to Article
Stewart AL, Greenfield S, Hays RD,  et al.  Functional status and well-being of patients with chronic conditions: results from the Medical Outcomes Study.  JAMA. 1989;262(7):907-913
PubMed   |  Link to Article
Hybels CF, Pieper CF, Blazer DG. The complex relationship between depressive symptoms and functional limitations in community-dwelling older adults: the impact of subthreshold depression.  Psychol Med. 2009;39(10):1677-1688
PubMed   |  Link to Article
Pollock ML, Gaesser GA, Butcher J,  et al.  American College of Sports Medicine Position Stand: the recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults.  Med Sci Sports Exerc. 1998;30(6):975-991
PubMed   |  Link to Article
Nelson ME, Rejeski WJ, Blair SN,  et al; American College of Sports Medicine; American Heart Association.  Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association.  Circulation. 2007;116(9):1094-1105
PubMed   |  Link to Article
Haskell WL, Lee IM, Pate RR,  et al; American College of Sports Medicine; American Heart Association.  Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association.  Circulation. 2007;116(9):1081-1093
PubMed   |  Link to Article
Physical Activity Guidelines Advisory Committee.  Physical Activity Guidelines Advisory Committee Report. Washington, DC: US Dept of Health and Human Services; 2008:1-683

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Flowchart of study selection. RCTs indicates randomized controlled trials.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Forest plot of unweighted distribution of Hedges d effect sizes.

Tables

Table Graphic Jump LocationTable 1. Annotated Descriptors of Unweighted Hedges d Effect Sizes
Table Graphic Jump LocationTable 2. Summary of Univariate Moderator Analysis

References

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Gary RA, Dunbar SB, Higgins MK, Musselman DL, Smith AL. Combined exercise and cognitive behavioral therapy improves outcomes in patients with heart failure.  J Psychosom Res. 2010;69(2):119-131
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Smith PJ, Blumenthal JA, Babyak MA, Georgiades A, Hinderliter A, Sherwood A. Effects of exercise and weight loss on depressive symptoms among men and women with hypertension.  J Psychosom Res. 2007;63(5):463-469
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Beck AT, Steer RA, Brown GK. Manual for the Beck Depression Inventory-2. San Antonio, TX: Psychological Corp; 1996
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PubMed   |  Link to Article
Hedges LV, Olkin I. Statistical Methods for Meta-analysis. New York, NY: Academic Press; 1985
Rosenthal R. Parametric measures of effect size. In: Cooper H, Hedges LV, eds. The Handbook of Research Synthesis. New York, NY: Russell Sage Foundation; 1994:231-244
Etnier JL, Karper WB, Gapin JI, Barella LA, Chang YK, Murphy KJ. Exercise, fibromyalgia, and fibrofog: a pilot study.  J Phys Act Health. 2009;6(2):239-246
PubMed
Flynn KE, Piña IL, Whellan DJ,  et al; HF-ACTION Investigators.  Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial.  JAMA. 2009;301(14):1451-1459
PubMed   |  Link to Article
Penninx BWJH, Rejeski WJ, Pandya J,  et al.  Exercise and depressive symptoms: a comparison of aerobic and resistance exercise effects on emotional and physical function in older persons with high and low depressive symptomatology.  J Gerontol B Psychol Sci Soc Sci. 2002;57(2):P124-P132
PubMed   |  Link to Article
Strömbeck BE, Theander E, Jacobsson LTH. Effects of exercise on aerobic capacity and fatigue in women with primary Sjögren's syndrome.  Rheumatology (Oxford). 2007;46(5):868-871
PubMed   |  Link to Article
Emery CF, Schein RL, Hauck ER, MacIntyre NR. Psychological and cognitive outcomes of a randomized trial of exercise among patients with chronic obstructive pulmonary disease.  Health Psychol. 1998;17(3):232-240
PubMed   |  Link to Article
Skrinar GS, Huxley NA, Hutchinson DS, Menninger E, Glew P. The role of a fitness intervention on people with serious psychiatric disabilities.  Psychiatr Rehabil J. 2005;29(2):122-127
PubMed   |  Link to Article
Leibetseder V, Strauss-Blasche G, Marktl W, Ekmekcioglu C. Does aerobic training enhance effects of spa therapy in back pain patients? a randomized, controlled clinical trial.  Forsch Komplementarmed. 2007;14(4):202-206
PubMed   |  Link to Article
Lim H-J, Moon Y-I, Lee MS. Effects of home-based daily exercise therapy on joint mobility, daily activity, pain, and depression in patients with ankylosing spondylitis.  Rheumatol Int. 2005;25(3):225-229
PubMed   |  Link to Article
Payne JK, Held J, Thorpe J, Shaw H. Effect of exercise on biomarkers, fatigue, sleep disturbances, and depressive symptoms in older women with breast cancer receiving hormonal therapy.  Oncol Nurs Forum. 2008;35(4):635-642
PubMed   |  Link to Article
Courneya KS, Segal RJ, Gelmon K,  et al.  Six-month follow-up of patient-rated outcomes in a randomized controlled trial of exercise training during breast cancer chemotherapy.  Cancer Epidemiol Biomarkers Prev. 2007;16(12):2572-2578
PubMed   |  Link to Article
Lipsey MW, Wilson DB. Practical Meta-analysis. Newbury Park, CA: Sage Publications; 2001
Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses.  BMJ. 2003;327(7414):557-560
PubMed   |  Link to Article
Rosenberg MS. The file-drawer problem revisited: a general weighted method for calculating fail-safe numbers in meta-analysis.  Evolution. 2005;59(2):464-468
PubMed
Rosenthal R, DiMatteo MR. Meta-analysis: recent developments in quantitative methods for literature reviews.  Annu Rev Psychol. 2001;52(1):59-82
PubMed   |  Link to Article
Dunn AL, Trivedi MH, O’Neal HA. Physical activity dose-response effects on outcomes of depression and anxiety.  Med Sci Sports Exerc. 2001;33(6):(suppl)  S587-S597, discussion 609-610
PubMed
Booth FW, Chakravarthy MV, Gordon SE, Spangenburg EE. Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy.  J Appl Physiol. 2002;93(1):3-30
PubMed
Stewart AL, Hays RD, Wells KB, Rogers WH, Spritzer KL, Greenfield S. Long-term functioning and well-being outcomes associated with physical activity and exercise in patients with chronic conditions in the Medical Outcomes Study.  J Clin Epidemiol. 1994;47(7):719-730
PubMed   |  Link to Article
Rosenthal R. Meta-analytic Procedures for Social Research. London, England: Sage Publications; 1991
Gleser LJ, Olkin I. Stochastically dependent effect sizes. In: Cooper H, Hedges LV, eds. The Handbook of Research Synthesis. New York, NY: Russell Sage Foundation; 1994:339-355
Kendall PC, Hollon SD, Beck AT, Hammen CL, Ingram RE. Issues and recommendations regarding use of the Beck Depression Inventory.  Cognit Ther Res. 1987;11(3):289-299Link to Article
Link to Article
Weissman MM, Sholomskas D, Pottenger M, Prusoff BA, Locke BZ. Assessing depressive symptoms in five psychiatric populations: a validation study.  Am J Epidemiol. 1977;106(3):203-214
PubMed
Crawford JR, Henry JD, Crombie C, Taylor EP. Normative data for the HADS from a large non-clinical sample.  Br J Clin Psychol. 2001;40(pt 4):429-434
PubMed   |  Link to Article
Rush AJ, Bernstein IH, Trivedi MH,  et al.  An evaluation of the Quick Inventory of Depressive Symptomatology and the Hamilton Rating Scale for Depression: a sequenced treatment alternative to relieve depression trial report.  Biol Psychiatry. 2006;59(6):493-501
PubMed   |  Link to Article
Yesavage JA, Brink TL, Rose TL,  et al.  Development and validation of a geriatric depression screening scale: a preliminary report.  J Psychiatr Res. 1982-1983;17(1):37-49
PubMed   |  Link to Article
Rooks DS, Gautam S, Romeling M,  et al.  Group exercise, education, and combination self-management in women with fibromyalgia: a randomized trial.  Arch Intern Med. 2007;167(20):2192-2200
PubMed   |  Link to Article
Puetz TW, O’Connor PJ, Dishman RK. Effects of chronic exercise on feelings of energy and fatigue: a quantitative synthesis.  Psychol Bull. 2006;132(6):866-876
PubMed   |  Link to Article
Hernández-Molina G, Reichenbach S, Zhang B, Lavalley M, Felson DT. Effect of therapeutic exercise for hip osteoarthritis pain: results of a meta-analysis.  Arthritis Rheum. 2008;59(9):1221-1228
PubMed   |  Link to Article
van Tol BAF, Huijsmans RJ, Kroon DW, Schothorst M, Kwakkel G. Effects of exercise training on cardiac performance, exercise capacity and quality of life in patients with heart failure: a meta-analysis.  Eur J Heart Fail. 2006;8(8):841-850
PubMed   |  Link to Article
Chen Y, Guo JJ, Zhan S, Patel NC. Treatment effects of antidepressants in patients with post-stroke depression: a meta-analysis.  Ann Pharmacother. 2006;40(12):2115-2122
PubMed   |  Link to Article
Häuser W, Bernardy K, Uçeyler N, Sommer C. Treatment of fibromyalgia syndrome with antidepressants: a meta-analysis.  JAMA. 2009;301(2):198-209
PubMed   |  Link to Article
Rosenthal R, Rubin DB. A simple, general purpose display of magnitude of experimental effect.  J Educ Psychol. 1982;74(2):166-169Link to Article
Link to Article
Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect.  BMJ. 1995;310(6977):452-454
PubMed   |  Link to Article
Mausbach BT, Chattillion EA, Moore RC, Roepke SK, Depp CA, Roesch S. Activity restriction and depression in medical patients and their caregivers: a meta-analysis.  Clin Psychol Rev. 2011;31(6):900-908
PubMed   |  Link to Article
Ziegelstein RC, Fauerbach JA, Stevens SS, Romanelli J, Richter DP, Bush DE. Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction.  Arch Intern Med. 2000;160(12):1818-1823
PubMed   |  Link to Article
Stewart AL, Greenfield S, Hays RD,  et al.  Functional status and well-being of patients with chronic conditions: results from the Medical Outcomes Study.  JAMA. 1989;262(7):907-913
PubMed   |  Link to Article
Hybels CF, Pieper CF, Blazer DG. The complex relationship between depressive symptoms and functional limitations in community-dwelling older adults: the impact of subthreshold depression.  Psychol Med. 2009;39(10):1677-1688
PubMed   |  Link to Article
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