Effects of Exercise on Depressive Symptoms in Adults With Arthritis and Other Rheumatic Disease

A Systematic Review of Meta-analyses

George A Kelley; Kristi S Kelley

BMC Musculoskelet Disord. 2014;15(121)

Discussion

Findings

The purpose of the current study was to conduct a systematic review of previous meta-analyses addressing the effects of exercise (aerobic, strength training or both) in the treatment of depressive symptoms in adults with osteoarthritis, rheumatoid arthritis, fibromyalgia or systemic lupus erythematous. While no meta-analyses were included for participants with osteoarthritis, rheumatoid arthritis or systemic lupus erythematous, two meta-analyses in fibromyalgia participants met the eligibility criteria.^[30,37] Generally speaking, it appears that exercise can reduce depressive symptoms in adults with fibromyalgia. This interpretation is supported by (1) the non-overlapping confidence intervals for SMDs, (2) statistical significance of the SMDs, (3) sensitivity of results with each study deleted from the model once, (4) cumulative meta-analysis, (5) low NNT, (6) absolute number of people in the US who might benefit by starting and maintaining an exercise program, (7) percentile improvements as a result of exercise and (8) good overall methodological quality of each meta-analysis as assessed by the AMSTAR instrument. However, for both,^[30,37] a statistically significant and relatively large amount of heterogeneity was observed as well as overlapping prediction intervals. In addition, small-study effects were found for the Hauser et al.^[37] meta-analysis and based on the work of others,^[44] may have been underpowered for the Busch et al.^[30] study. Consequently, the strength of the overall findings may be weakened by these results.

The overall findings of the included meta-analyses compare quite favorably to the effects of pharmacologic interventions on depressive symptoms in adults with fibromyalgia. For example, Hauser et al.^[45] conducted a meta-analysis of randomized controlled trials on the effects of antidepressants (tricyclic and tetracyclic antidepressants, selective serotonin reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors, monoamine oxidase inhibitors) on depressed mood in adults with fibromyalgia. Across 10 SMDs that included 887 participants (451 treatment, 436 control) a small SMD improvement of -0.26 (95% CI, -0.39, -0.12, p < 0.001) was reported. However, in contrast to the exercise meta-analyses included in the current study,^[30,37] no statistically significant heterogeneity was observed (Q = 6.39, p = 0.70, I² = 0%). Thus, while the effects of antidepressants were generally smaller,^[45] the results were more consistent than the two exercise meta-analyses included in the current study.^[30,37] The former notwithstanding, one should also consider the potential side-effects and costs of any type of pharmacotherapy, including antidepressants.

Implications for Research

The results of the current systematic review of previous meta-analyses have at least eight implications for future research. First, while the overall quality of both meta-analyses was considered to be good, there are several areas that might be improved upon in future meta-analytic work. These include avoiding the use of publication status as an inclusion criterion as well as documenting and providing a list of not only included studies but also excluded studies, including the reasons for exclusion. While there is little doubt in the investigators' minds regarding the latter recommendation, avoiding the use of publication status as an inclusion criterion could be questioned. For example, van Driel et al. suggested that (1) the difficulty in retrieving unpublished work could lead to selection bias, (2) many unpublished trials are eventually published, (3) the methodological quality of such studies are poorer than those that are published, and (4) the effort and resources required to obtain unpublished work may not be warranted.^[46]

Second, both included studies were aggregate data meta-analyses.^[30,37] While still the most common type of meta-analysis, individual-participant data meta-analyses (IPD) have been suggested to be the gold standard when attempting to quantitatively combine data from different studies on the same topic.^[47] Thus, future meta-analysts may want to consider using the IPD approach when addressing the effects of exercise in the treatment of depressive symptoms in adults with arthritis and other rheumatic diseases. However, the use of the IPD approach needs to be considered with respect to the ability to retrieve IPD from investigators as well as the increased costs and time associated with the conduct of such.^[48]

Third, given the apparent paucity of data available on adverse events and cost-effectiveness in the original studies included in both meta-analyses,^[30,37] there is a need for future randomized controlled trials to collect and report this information. The inclusion of such information is critical when making decisions regarding which interventions to recommend over others.

Fourth, the dose–response effects of exercise on depressive symptoms in adults with fibromyalgia are still unknown. While the meta-analysis by Hauser et al. found no statistically significant differences between either low or moderate intensity aerobic exercise and land versus water-based exercise,^[37] future research in this area appears warranted. Greater knowledge of the dose–response effects of exercise on depressive symptoms in adults with fibromyalgia should lead to better treatment in this population.

Fifth, no meta-analysis that was limited to the effects of exercise on depressive symptoms in adults with osteoarthritis, rheumatoid arthritis or systemic lupus erythematous met the eligibility criteria for the current study. Since the effects of exercise on depressive symptoms may vary across different populations, it appears plausible to suggest that future meta-analytic work be limited and focused on these groups. This is of course assuming that previous randomized controlled trials have assessed depressive symptoms in these populations.

Sixth, because neither meta-analysis reported NNT with respect to depressive symptoms,^[30,37] it is suggested that future meta-analytic work include such. From the investigators' perspective, the inclusion of such information is important because it provides practically relevant information to decision-makers (practitioners, policy-makers, etc.) regarding the effects of exercise on depressive symptoms in adults with fibromyalgia.

Seventh, given the significant heterogeneity in the included meta-analyses, future meta-analytic research on depressive symptoms in adults with fibromyalgia should try and identify the sources of this heterogeneity. Broadly, this may include such things as participant characteristics (for example, age, gender), intervention characteristics (for example, length, frequency, intensity, duration, mode) and outcome assessment methods (for example, type of instrument used to assess depression). Again, this is of course assuming that sufficient data are available to examine these potential predictors.

Eighth, the majority of the participants that comprised both meta-analyses were women.^[30,37] The inclusion of primarily women for the studies nested within each meta-analysis appears plausible given that the prevalence of fibromyalgia is greater in women than men.^[4] However, it would appear appropriate to suggest that future research examine the effects of exercise on depressive symptoms in men to ensure that no differences in response exist.

Implications for Practice

The results of the current systematic review of previous meta-analyses have important implications for practice. First, while there was a lack of adverse event and cost-effectiveness data as well as substantial between-study heterogeneity in both meta-analyses,^[30,37] exercise appears to improve depressive symptoms in adults with fibromyalgia and could be recommended as part of an overall treatment plan that may also include education and/or pharmacotherapy. This exercise recommendation is consistent with previous recommendations on aerobic and strength training for a variety of outcomes in adults with fibromyalgia.^[49,50] Second, while the dose–response effects of exercise in the treatment of depressive symptoms in adults with fibromyalgia have not been firmly established,^[51] it would appear prudent to recommend that practitioners follow the general recommendations described by Skinner.^[51] These include exercise programs that (1) minimize any increase in pain, fatigue or other symptoms, (2) begin at a low level and progress gradually, (3) allow for day to day variations based on how the participant feels, (4) improve the physiological and psychological functioning of the participant and (5) promote long-term adherence.^[51] More specifically, a combined program of low to moderate intensity aerobic exercise (walking and swimming for example) combined with low to moderate intensity strength training may be better tolerated than high intensity activity.^[51] Given the day to day variation in how fibromyalgia participants may feel, intensity may be better monitored using something like rating of perceived exertion scales^[52–55] versus a percentage of 1-repetition maximum (strength training) and maximum heart rate, heart rate reserve or percentage of maximum oxygen consumption (aerobic training).^[51]

Strengths and Potential Limitations of Current Study

There are at least five strengths of the current study. First, to the best of the authors' knowledge, this is the first systematic review of previous meta-analyses that has examined the effects of exercise on depressive symptoms in adults with arthritis and other rheumatic disease, an increasingly important approach for addressing the effects of various healthcare interventions and making subsequent decisions regarding such.^[11] Second, the additional analyses conducted based on the available data (small-study effects, influence analysis, NNT, etc.), helped strengthen the information from which conclusions could be drawn from both included meta-analyses.^[30,37] Third, the calculation and inclusion of PIs for the overall results from each included meta-analysis provides investigators with information that can aid them in planning future randomized controlled trials examining the effects of exercise on depressive symptoms in adults with fibromyalgia. Fourth, the investigative team believes that the calculation of percentile improvements, NNT and gross estimates of the absolute number of adults with fibromyalgia who could improve their depressive symptoms by initiating and maintaining a program of regular exercise enhances the practical applicability and importance of findings. Fifth, while the inclusion of only two meta-analyses may initially appear to be a limitation of the current study, the investigators view this as a strength given that as many as 32 SMDs on depressive symptoms in as many as 870 participants across multiple studies were included. To put this in perspective, the Cochrane Collaboration suggests that the minimum number of studies needed to conduct a meta-analysis is two.^[8] Given this line of thinking, it would appear plausible to suggest that the minimum number of meta-analyses that need to be included in a study of systematic reviews with meta-analyses is one.

While there are several strengths of the current study, there are also at least four potential limitations. First, the investigative team focused on depressive symptoms.^[30,37] While more focused and applicable, other relevant outcomes (anxiety, quality of life, quality of sleep, pain, fatigue, stiffness, physical function) were not captured. Second, the gross population estimates for the number of people in the US with fibromyalgia who could improve their depressive symptoms by beginning and maintaining a regular exercise program assumed that none of those with fibromyalgia in the US exercise on a regular basis. Unfortunately, the investigative team is not aware of any current research on the prevalence of physical activity in US adults with fibromyalgia, and thus, was unable to adjust for such. In addition, it was not possible to adjust for any other potentially confounding factors (for example, age). Therefore, the reported estimates might be inflated. Third, as with any systematic review, many of the biases inherent in both the included meta-analyses as well as the randomized controlled trials that comprised each meta-analysis may have also been present in the current study. Fourth, while results were generalized to both men and women, the majority of participants included in both meta-analyses were women.^[30,37] Thus, such a generalization may have been inappropriate.

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Table 1. General characteristics of included meta-analyses.
Reference	Year	Studies	Participants	Interventions
Busch et al. [30]	2007	6	294 primarily women (154 exercise, 137 control), all with fibromyalgia, 33–50 years of age (X̄ ± SD; 41.1 ± 5.2)	Supervised/unsupervised aerobic and strength training interventions lasting 6 to 23 weeks (X̄ ± SD, 14 ± 7 weeks), frequency (2–5x week), duration (18–90 minutes per session), intensity (aerobic, 40% -75% HRR; strength, 40%-80% 1RM)
Hauser et al. [37]	2010	18	870 primarily women (456 exercise, 414 control), all with fibromyalgia, 35–56 years of age (X̄ ± SD; 46.6 ± 5.2)	Supervised/unsupervised aerobic exercise lasting 6–26 weeks (X̄ ± SD, 13 ± 6), frequency (1–7x week; X̄ ± SD, 3 ± 1), duration (15–45 minutes per session; X̄ ± SD, 31 ± 10), intensity (40%-85% MHR), compliance (38%–92%; X̄ ± SD, 62 ± 19)

Notes: X̄ ± SD, mean ± standard deviation; HRR, heart rate reserve; RM, repetition maximum, MHR, maximum heart rate; Description of meta-analyses limited to those related to depressive symptoms as the outcome; Data presented limited to that which was reported or could be calculated from reported data.

Table 2. Overall post-treatment standardized mean difference (SMD) effect sizes for depressive symptoms from included meta-analyses
Reference	ES/Participants (No.)	SMD (95% CI)	Z(p)	Q (p)	I ^{2 (%)}	τ²	PI (95%)
Busch et al. (2006) [30]^a	6/294	-0.61 (-0.99 to -0.23)	-3.12(0.002)*	12.0 (0.04)**	58.4	0.13	-1.74, 0.53
Hauser et al. (2010) [37]	19/870	-0.32 (-0.53 to -0.12)	-3.13(0.002)*	37.0 (0.005)**	51.4	0.22	-1.32, 0.68

Notes: No, Number; ES, effect size; SMD, standardized mean difference; 95% CI, 95% confidence intervals; Z(p), Z-value and probability value for Z; Q(p), Cochran's Q statistic and associated alpha (p) value for Q; I ², I-squared statistic for heterogeneity; τ², tau-squared; PI, prediction intervals, based on a random-effects model; SMD (95% CI) based on random-effects model; Boldfaced values indicate continuous data with non-overlapping confidence intervals; *, statistically significant, p ≤ 0.05; **, statistically significant, p ≤ 0.10;^a, original meta-analysis did not pool results as done here, but rather, reported separate subgroup results for aerobic exercise studies meeting the American College of Sports Medicine recommendations [31,32] (4 studies), those not meeting the recommendations (1 study) and those limited to strength training exercise (1 study).

Table 3. NNT, number whose depressive symptoms could benefit from exercise, and percentile improvement
Reference	NNT (95% CI)	Number Benefitting (95% CI) (millions)^a	U₃ Index (95% CI)^b (Percentile Improvement)
Busch et al. (2006) [30]	6 (4, 13)	0.83 (1.25, 0.38)	22.9 (9.1, 33.9)
Hauser et al. (2010) [37]	9 (6, 23)	0.56 (0.83, 0.22)	12.6 (4.8, 20.2)

Notes: NNT, number needed to-treat; 95% CI, 95% confidence intervals; ^a, gross estimate of the number of US people with fibromyalgia who could improve their depressive symptoms if they started and maintained a regular exercise program. Based on an estimated 5 million US people with fibromyalgia [4] and assuming that none exercise regularly; ^b, Cohen's U₃ Index [38].

Additional File 3. Item by item results using the AMSTAR assessment instrument[20–23].
Question	Busch et al. [30]	Hauser et al. [37]
1. Was an 'a priori' design provided? The research question and inclusion criteria should be established before the conduct of the review.	Yes	Yes
2. Was there duplicate study selection and data extraction? There should be at least two independent data extractors and a consensus procedure for disagreements should be in place.	Yes	Yes
3. Was a comprehensive literature search performed? At least two electronic sources should be searched. The report must include years and databases used (e.g. Central, EMBASE, and MEDLINE). Key words and/or MESH terms must be stated and where feasible the search strategy should be provided. All searches should be supplemented by consulting current contents, reviews, textbooks, specialized registers, or experts in the particular field of study, and by reviewing the references in the studies found.	Yes	Yes
4. Was the status of publication (i.e. grey literature) as an inclusion criterion avoided? The authors should state that they searched for reports regardless of their publication type. The authors should state whether or not they excluded any reports (from the systematic review), based on their publication status, language etc.	Cannot answer	No
5. Was a list of studies (included and excluded) provided? A list of included and excluded studies should be provided.	Yes	No
6. Were the characteristics of the included studies provided? In an aggregated form such as a table, data from the original studies should be provided on the participants, interventions and outcomes. The ranges of characteristics in all the studies analyzed e.g. age, race, sex, relevant socioeconomic data, disease status, duration, severity, or other diseases should be reported.	Yes	Yes
7. Was the scientific quality of the included studies assessed and documented? 'A priori' methods of assessment should be provided (e.g., for effectiveness studies if the author(s) chose to include only randomized, double-blind, placebo controlled studies, or allocation concealment as inclusion criteria); for other types of studies alternative items will be relevant.	Yes	Yes
8. Was the scientific quality of the included studies used appropriately in formulating conclusions? The results of the methodological rigor and scientific quality should be considered in the analysis and the conclusions of the review, and explicitly stated in formulating recommendations.	Yes	Yes
9. Were the methods used to combine the findings of studies appropriate? For the pooled results, a test should be done to ensure the studies were combinable, to assess their homogeneity (i.e. Chi-squared test for homogeneity, I²). If heterogeneity exists a random effects model should be used and/or the clinical appropriateness of combining should be taken into consideration (i.e. is it sensible to combine?).	Yes	Yes
10. Was the likelihood of publication bias assessed? An assessment of publication bias should include a combination of graphical aids (e.g., funnel plot, other available tests) and/or statistical tests (e.g., Egger regression test).	Yes	Yes
11. Was the conflict of interest stated? Potential sources of support should be clearly acknowledged in both the systematic review and the included studies.	Yes	Yes
Notes: Possible responses were "Yes", "No", "Can't Answer", "Not Applicable". "Can't Answer" chosen when item is relevant but not described. "Not Applicable" chosen when item is not relevant (for example, meta-analysis not possible) [20–23].

Additional File Information

File Name: Arthritis_Depression_SR_MA_BMCMD_Additional File 1
File format: MS Word 2010, extension = .docx
Title of Data: Search strategies for databases searched.
Description of Data: This additional file provides a description of the search strategy used for each database searched.

File Name: Arthritis_Depression_SR_MA_BMCMD_Additional File 2
File format: MS Word 2010, extension = .docx
Title of Data: Studies excluded, including reasons for exclusion.
Description of Data: This additional file provides a list of excluded studies, including the reasons for exclusion.

File Name: Arthritis_Depression_SR_MA_BMCMD_Additional File 3
File format: MS Word 2010, extension = .docx
Title of Data: Item by item results using the AMSTAR assessment instrument
Description of Data: This additional file provides item by item results of methodological quality using the AMSTAR assessment instrument.

Additional File 2.
	Additional File 2. Studies excluded, including reasons for exclusion. (1) Bariatric surgery for people with diabetes and morbid obesity: an evidence-based analysis. Ontario Health Technolology Assessment Services 2009;9(22):1-23. Inappropriate Population, Inappropriate Intervention (2) Management of fibromyalgia. Drug and Therapeutics Bulletin 2010;48(8):89-93. Inappropriate Study Design (3) Adler PA. The effects of Tai Chi on pain and function in older adults with osteoarthritis. Cleveland. Case Western Reserve University; 2007. Inappropriate Study Design (4) Allen LA, Escobar J, I, Lehrer PM, Gara MA, Woolfolk RL. Psychosocial treatments for multiple unexplained physical symptoms: a review of the literature. Psychosomatic Medicine 2002;64(6):939-50. Inappropriate Population (5) Barlow J, Singh D, Bayer S, Curry R. A systematic review of the benefits of home telecare for frail elderly people and those with long-term conditions. Journal of Telemedicine and Telecare 2007;13(4):172-9. Inappropriate Study Design, Inappropriate Intervention (6) Beltran R. The effects of a supervised group aerobic exercise program and a chronobiologically oriented treatment protocol on symptomatology and mood in women with fibromyalgia. Alliant International University, San Diego; 2003. Inappropriate Study Design (7) Bernardy K, Fuber N, Kollner V, Hauser W. Efficacy of cognitive-behavioral therapies in fibromyalgia syndrome: a systematic review and metaanalysis of randomized controlled trials. Journal of Rheumatology 2010;37(10):1991-2005. Inappropriate Intervention, Inappropriate Comparison Group (8) Berzins K, Reilly S, Abell J, Hughes J, Challis D. UK self-care support initiatives for older patients with long-term conditions: a review. Chronic Illness 2009;5(1):56-72. Inappropriate Population (9) Borkhoff CM, Wieland ML, Myasoedova E, Ahmad Z, Welch V, Hawker GA, Li LC, Buchbinder R, Ueffing E, Beaton D, Cardiel MH, Gabriel SE, Guillemin F, Adebajo AO, Bombardier C, Hajjaj-Hassouni N, Tugwell P. Reaching those most in need: a scoping review of interventions to improve health care quality for disadvantaged populations with osteoarthritis. Arthritis Care and Research 2011;63(1):39-52. Inappropriate Study Design, Inappropriate Outcomes (10) Brosseau, L., Wells, G. A., Tugwell, P., Egan, M., Wilson, K. G., Dubouloz, C. J., Casimiro, L., Robinson, V. A., McGowan, J., Busch, A., Poitras, S., Moldofsky, H., Harth, M., Finestone, H. M., Nielson, W., Haines-Wangda, A., Doreleyers, M. R., Lambert, K., Marshall, A. D., Veilleux, L., Busch, A., Poitras, S., Moldofsky, H., Harth, M., Finestone, H. M., Nielson, W., Haines-Wangda, A., Russel-Doreleyers, M., Lambert, K., Marshall, A. D., and Veilleux, L. Ottawa Panel evidence-based clinical practice guidelines for aerobic fitness exercises in the management of fibromyalgia: Part 1. Physical Therapy 88(7), 857-871. 2008. Inappropriate Study Design (11) Brosseau, L., Wells, G. A., Tugwell, P., Egan, M., Wilson, K. G., Dubouloz, C. J., Casimiro, L., Robinson, V. A., McGowan, J., Busch, A., Poitras, S., Moldofsky, H., Harth, M., Finestone, H. M., Nielson, W., Haines-Wangda, A., Russell-Doreleyers, M., Lambert, K., Marshall, A. D., and Veilleux, L. Ottawa Panel evidence-based clinical practice guidelines for strengthening exercises in the management of fibromyalgia: Part 2. Physical Therapy 88(7), 873-886. 2008. Inappropriate Study Design (12) Calandre EP, Rico-Villademoros F. The role of antipsychotics in the management of fibromyalgia. CNS Drugs 2012 February 1;26(2):135-53. Inappropriate Study Design, Inappropriate Intervention (13) Cancelliere C. Are workplace health promotion/wellness programs effective at improving presenteeism (on-the-job productivity) in workers? A systematic review and best evidence synthesis of the literature. Lakehead University (Canada); 2011. Inappropriate Study Design, Inappropriate Population, Inappropriate Outcomes (14) Carnes D, Homer KE, Miles CL, Pincus T, Underwood M, Rahman A, Taylor SJ. Effective delivery styles and content for self-management interventions for chronic musculoskeletal pain: a systematic literature review. Clinical Journal of Pain 2012;28(4):344-54. Inappropriate Population (15) Carville SF, Choy EHS. Systematic review of discriminating power of outcome measures used in clinical trials of fibromyalgia. Journal of Rheumatology 2008;35(11):2094-105. Inappropriate Intervention, Inappropriate Comparison Group (16) Carville SF, Arendt-Nielsen S, Bliddal H, Blotman F, Branco JC, Buskila D, Da Silva JAP, Danneskiold-Samsoe B, Dincer F, Henriksson C, Henriksson KG, Kosek E, Longley K, McCarthy GM, Perrot S, Puszczewicz M, Sarzi-Puttini P, Silman A, Spath M, Choy EH. EULAR evidence-based recommendations for the management of fibromyalgia syndrome. Annals of the Rheumatic Diseases 2008;67(4):536-41. Inappropriate Study Design (17) Cazzola M, Atzeni F, Salaffi F, Stisi S, Cassisi G, Sarzi-Puttini P. Which kind of exercise is best in fibromyalgia therapeutic programmes? A practical review. Clinical and Experimental Rheumatology 2010 November;28(6 Suppl 63):S117-S124. Inappropriate Study Design (18) Centre for Reviews and Dissemination. Systematic review of the clinical effectiveness of self care support networks in health and social care. Report. 2006. Inappropriate Intervention, Inappropriate Study Design, (19) D'Silva S, Poscablo C, Habousha R, Kogan M, Kligler B. Mind-body medicine therapies for a range of depression severity: A systematic review. Psychosomatics 2012;53(5):407-23. Inappropriate Study Design (20) Dagfinrud H, Halvorsen S, Vollestad NK, Niedermann K, Kvien TK, Hagen KB. Exercise programs in trials for patients with ankylosing spondylitis: Do they really have the potential for effectiveness? Arthritis Care and Research 2011;63(4):597-603. Inappropriate Study Design, Inappropriate Outcomes (21) Epstein I, Stinson J, Stevens B. The effects of camp on health-related quality of life in children with chronic illnesses: a review of the literature. Journal of Pediatric Oncology Nursing 2005;22(2):89-103. Inappropriate Population, Inappropriate Study Design (22) Garcia-Campayo J, Magdalena J, Magallon R, Fernandez-Garcia E, Salas M, Andres E. A meta-analysis of the efficacy of fibromyalgia treatment according to level of care. Arthritis Research and Therapy 2008;10(4). Inappropriate Intervention, Inappropriate Comparison Group (23) Gellis ZD, Kang-Yi C. Meta-analysis of the effect of cardiac rehabilitation interventions on depression outcomes in adults 64 years of age and older. American Journal of Cardiology 2012 November 1;110(9):1219-24. Inappropriate Population (24) Glombiewski JA, Sawyer AT, Gutermann J, Koenig K, Rief W, Hofmann SG. Psychological treatments for fibromyalgia: A meta-analysis. Pain 2010;151(2):280-95. Inappropriate Intervention (25) Grossman P, Niemann L, Schmidt S, Walach H. Mindfulness-based stress reduction and health benefits: a meta-analysis. Journal of Psychosomatic Research 2004;57(1):35-43. Inappropriate Outcomes (26) Hadhazy VA, Ezzo J, Creamer P, Berman BM. Mind-body therapies for the treatment of fibromyalgia: a systematic review. Journal of Rheumatology 2000;27(12):2911-8. Inappropriate Study Design (27) Han TS, Tajar A, Lean ME. Obesity and weight management in the elderly. British Medical Bulletin 2011;97:169-96. Inappropriate Population, Inappropriate Outcomes (28) Hauser W, Bernardy K, Arnold B, Offenbacher M, Schiltenwolf M. Efficacy of multicomponent treatment in fibromyalgia syndrome: A meta-analysis of randomized controlled clinical trials. Arthritis Care and Research 2009;61(2):216-24. Inappropriate Intervention, Inappropriate Comparison Group (29) Hauser W, Thieme K, Turk DC. Guidelines on the management of fibromyalgia syndrome - A systematic review. European Journal of Pain 2010;14(1):5-10. Inappropriate Study Design (30) Herring MP, Puetz TW, O'Connor PJ, Dishman RK. Effect of exercise training on depressive symptoms among patients with a chronic illness: A systematic review and meta-analysis of randomized controlled trials. Archives of Internal Medicine 2012;172 (2):101-111. Inappropriate Population (31) Holdcraft LC, Assefi N, Buchwald D. Complementary and alternative medicine in fibromyalgia and related syndromes. Best Practice and Research in Clinical Rheumatology 2003;17(4):667-83. Inappropriate Study Design, Inappropriate Intervention (32) Imamura M, Cassius DA, Fregni F. Fibromyalgia: From treatment to rehabilitation. European Journal of Pain 2009 November 1;3(2):117-22. Inappropriate Study Design (33) Jones KD, Deodhar P, Lorentzen A, Bennett RM, Deodhar AA. Growth hormone perturbations in fibromyalgia: a review. Semininars in Arthritis and Rheumatism 2007 June;36(6):357-79. Inappropriate Intervention, Inappropriate Outcomes (34) Karmisholt K, Gotzcshe PC. Physical activity for secondary prevention of disease - Systematic reviews of randomised clinical trials. Danish Medical Bulletin 2005;52(2):90-4. Inappropriate Study Design (35) Keysor JJ, Jette AM. Have we oversold the benefit of late-life exercise? Journals of Gerontology Series A - Biological Sciences and Medical Sciences 2001;56A(7):M412-M423. Inappropriate Study Design, Inappropriate Population (36) Kiepe MS, Stockigt B, Keil T. Effects of dance therapy and ballroom dances on physical and mental illnesses: A systematic review. Arts in Psychotherapy 2012;39(5):404-11. Inappropriate Study Design (37) Knittle K, Maes S, de G, V. Psychological interventions for rheumatoid arthritis: examining the role of self-regulation with a systematic review and meta-analysis of randomized controlled trials. Arthritis Care and Research 2010 October;62(10):1460-72. Inappropriate Intervention, Inappropriate Comparison Group (38) Kovar PA. Impact of a supervised walking and education program on functional status: Results from a randomized controlled trial in patients with osteoarthritis of the knee. Columbia University Teachers College; 1991. Inappropriate Study Design (39) Kroenke K. Efficacy of treatment for somatoform disorders: a review of randomized controlled trials. Psychosomatic Medicine 2007;69(9):881-8. Inappropriate Study Design, Inappropriate Population (40) La MK, Marks R. The efficacy of aerobic exercises for treating osteoarthritis of the knee. New Zealand Journal of Physiotherapy 1995;23(2):23-30. Inappropriate Study Design (41) Lange AK, Vanwanseele B, Fiatarone Singh MA. Strength training for treatment of osteoarthritis of the knee: a systematic review. Arthritis and Rheumatism (Arthritis Care and Research) 2008 October 15;59(10):1488-94. Inappropriate Study Design (42) Langhorst J, Klose P, Dobos GJ, Bernardy K, Hauser W. Efficacy and safety of meditative movement therapies in fibromyalgia syndrome: a systematic review and meta-analysis of randomized controlled trials. Rheumatology International 2013;33 (1):193-207. Inappropriate Population (43) Lee MS, Pittler MH, Ernst E. Tai chi for rheumatoid arthritis: systematic review. Rheumatology 2007 November;46(11):1648-51. Inappropriate Study Design (44) Lima, T. B., Dias, J. M., Mazuquin, B. F., da Silva, C. T., Nogueira, R. M. P., Marques, A. P., Lavado, E. L., and Cardoso, J. R. The effectiveness of aquatic physical therapy in the treatment of fibromyalgia: a systematic review with meta-analysis. Clinical Rehabilitation 27(10), 892-908. 2013. (45) Luciano JV, Martinez N, Penarrubia-Maria MT, Fernandez-Vergel R, Garcia-Campayo J, Verduras C, Blanco ME, Jimenez M, Ruiz JM, del Hoyo YL, Serrano-Blanco A. Effectiveness of a psychoeducational treatment program implemented in general practice for fibromyalgia patients: A randomized controlled trial. Clinical Journal of Pain 2011;27(5):383-91. Inappropriate Study Design (46) Mannerkorpi K, Iversen MD. Physical exercise in fibromyalgia and related syndromes. Best Practice and Research: Clinical Rheumatology 2003;17(4):629-47. Inappropriate Study Design (47) Mansky P, Sannes T, Wallerstedt D, Ge A, Ryan M, Johnson LL, Chesney M, Gerber L. Tai chi chuan: mind-body practice or exercise intervention? Studying the benefit for cancer survivors. Integrative Cancer Therapies 2006;5(3):192-201. Inappropriate Study Design, Inappropriate Population (48) McIlvane JM, Baker TA, Mingo CA, Haley WE. Are behavioral interventions for arthritis effective with minorities? Addressing racial and ethnic diversity in disability and rehabilitation. Arthritis and Rheumatism (Arthritis Care and Research) 2008;59(10):1512-8. Inappropriate Study Design, Inappropriate Population (49) McVeigh JG, McGaughey H, Hall M, Kane P. The effectiveness of hydrotherapy in the management of fibromyalgia syndrome: a systematic review. Rheumatology International 2008;29(2):119-30. Inappropriate Study Design, Inappropriate Outcomes (50) Minor MA. Exercise maintenance behavior of subjects with arthritis following participation in a supervised exercise program. University of Missouri - Columbia; 1989. Inappropriate Study Design (51) Onubogu U. Relationships among pain, pain medication, and pain outcomes in older adults with arthritis. 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