review
Neuropsychiatr
https://doi.org/10.1007/s40211-022-00431-2
Exercise training and depression and anxiety in
musculoskeletal pain patients: a meta-analysis of
randomized control trials
Sohrab Amiri
Received: 7 May 2022 / Accepted: 14 August 2022
© The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, ein Teil von Springer Nature 2022
Summary
Background Depression and anxiety in patients with
musculoskeletal pain harm health and exercise can
be effective in improving the condition of these pa-
tients. This study was aimed at systematically review-
ing and providing a meta-analysis of the effect of ex-
ercise training on improving depression and anxiety
in patients with musculoskeletal pain.
Methods The search was done in three databases in-
cluding PubMed, the Cochrane Library, and Google
Scholar up to August 2021. For each of the studies in-
cluded in the meta-analysis, the mean, standard de-
viation, and sample size were extracted in the post-
test, and the effect size was calculated. Publication
bias and heterogeneity were assessed in studies at the
end of the analysis.
Results Nineteen randomized control trials were in-
cluded in the meta-analysis. Exercise training has
a positive effect on depression in patients with mus-
culoskeletal pain, so exercise reduces depression and
Hedges’ g was equal to –0.21, with confidence inter-
vals of –0.40, –0.02. Exercise training has a positive ef-
fect on anxiety in patients with musculoskeletal pain,
so exercise reduces anxiety and Hedges’ g was equal
to –0.63, with confidence intervals of –1.08, –0.19.
Conclusions It was found that exercise training is ef-
fective in improving depression and anxiety in pa-
tients with musculoskeletal pain and therefore this
treatment should be given more attention from clini-
cal specialists.
We have used the PRISMA protocol and the Cochrane
Collaboration for this study, which can be used for free.
S. Amiri ()
Medicine, Quran and Hadith Research Center, Baqiyatallah
University of Medical Sciences, Tehran, Iran
Amirysohrab@yahoo.com
K Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . .
Keywords Anxiety · Depression · Exercise training ·
Meta-analysis · Systematic review
Bewegungstraining und Depressionen und
Angstzustände bei Patienten mit
muskuloskeletalen Schmerzen: eine
Metaanalyse randomisierter Kontrollstudien
Zusammenfassung
Grundlagen Depressionen und Angstzustände bei
Patienten mit Schmerzen des muskuloskeletalen Sys-
tems beeinträchtigen die Gesundheit. Bewegung kann
den Zustand dieser Patienten wirksam verbessern. Ziel
dieser Studie war es, die Wirkung von Bewegungstrai-
ning auf die Verbesserung von Depressionen und
Angstzuständen bei Patienten mit Schmerzen des
Bewegungsapparats systematisch zu überprüfen und
eine Metaanalyse zu erstellen.
Methodik Die Suche erfolgte in drei Datenbanken
(PubMed, Cochrane Library und Google Scholar) bis
August 2021. Für jede der in die Metaanalyse einge-
schlossenen Studien wurden im Posttest der Mittel-
wert, die Standardabweichung und die Stichproben-
größe extrahiert sowie die Effektgröße berechnet. Am
Ende der Analyse wurden Publikationsfehler und He-
terogenität in den Studien bewertet.
Ergebnisse In die Metaanalyse wurden 19 randomi-
sierte Kontrollstudien einbezogen. Bewegungstraining
hat einen positiven Effekt auf Depressionen bei Pati-
enten mit muskuloskeletalen Schmerzen, d. h. Bewe-
gung reduziert Depressionen (Hedges’ g = –0,21; Kon-
fidenzintervall –0,40 bis –0,02). Bewegungstraining hat
einen positiven Effekt auf die Angst von Patienten mit
muskuloskeletalen Schmerzen, d. h. Bewegung redu-
ziert die Angst (Hedges’ g = –0,63; Konfidenzintervall
–1,08 bis –0,19).
Schlussfolgerungen Es wurde festgestellt, dass Bewe-
gungstraining Depressionen und Angstzustände bei
 review
Patienten mit muskuloskeletalen Schmerzen wirksam
lindern kann, weshalb diese Behandlung von klini-
schen Spezialisten stärker berücksichtigt werden soll-
te.
Schlüsselwörter Ängste · Depressionen ·
Bewegungstraining · Metaanalyse · Systematischer
Review
Introduction
Musculoskeletal conditions are one of the most com-
mon diseases that has a great negative impact on
health. According to the Global Burden of Disease,
1.71 billion people have this condition [1]. These con-
ditions are characterized by pain and disability and
can therefore lead to a decrease in physical and men-
tal health [2]. Back pain and neck pain are among the
most debilitating types of musculoskeletal pain [3].
Low back pain is the most common musculoskele-
tal condition, affecting 568 million people worldwide
[1]. Although the prevalence of musculoskeletal pain
increases with age, people at younger ages are also af-
fected by the disease [4]. The prevalence of low back
pain was 36.8% and the prevalence of neck pain was
18.4% [5]. According to a 2017 study, musculoskele-
tal pain was responsible for 139 million disability-
adjusted life years (DALYs) and low back pain, with
64.9 million DALYs, has the highest burden of any
musculoskeletal condition [6] and 95% of the burden
of the musculoskeletal condition is due to disability
[7]. Musculoskeletal pain is associated with chronic
diseases [8], cardiovascular diseases [9], heart failure
[10], and mortality [11]. In this regard, studies show
a higher risk of depression and anxiety in people with
musculoskeletal pain than in the general population
[12–16].
Depression is one of the most common mental dis-
orders in the world [17], with a 1-month prevalence
of 5% in the community and a 12-monthly incidence
rate of more than 9% [18] and the lifetime prevalence
of depression is between 15 and 18% [19]. In pri-
mary care, on average, 1 in 10 people have depressive
symptoms [20]. The lifetime prevalence of depres-
sion in women is almost twice that of men, and in
both sexes, the prevalence of depression in the sec-
ond and third decades of life is high [21–24]. In 2008,
the World Health Organization ranked depression as
the third leading burden of disease worldwide, and it
is predicted that by 2030, depression will become the
leading burden of disease [25]. Anxiety disorders are
one of the most common mental disorders [26, 27],
and have a far-reaching impact on patients and soci-
ety, accounting for 3% of the global burden of disease,
with a cost of  74 million in 30 European countries
[28]. One of the methods of intervention in the treat-
ment of depressive and anxiety disorders is exercise
training [29–31].
Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . .
Exercise training is known to be an effective in-
tervention in the treatment of musculoskeletal pain
[32–36], improving clinical outcomes in patients with
metabolic syndrome [37], reducing the risk of cardio-
vascular disease [38, 39], improving sleep [40–42], and
reducing the risk of mortality in patients with chronic
heart failure [43]. In this regard, studies in the form of
systematic review or meta-analysis have examined the
effects of exercise on depression and anxiety [29–31,
44–49]. These studies show the effect of exercise train-
ing on depression and anxiety in the general popula-
tion or some groups of patients. Although depression
and anxiety are common problems in patients with
musculoskeletal pain, particularly in low back pain
and neck pain patients [12–16], so far no meta-analy-
sis study has examined the effect of exercise training
on improving depression and anxiety in patients with
musculoskeletal pain. On the other hand, the low rate
of diagnosis and treatment of depression and anxiety
in the general population and patients is concerning,
especially in low-income countries [50, 51]. Accord-
ingly, the purpose of this study was to systematically
review and provide a meta-analysis of the effect of ex-
ercise training on depression and anxiety in patients
with musculoskeletal pain. A separate analysis based
on low back pain and neck pain was another goal of
this study.
Methods
Search strategy
The Preferred Reporting Items for Systematic Reviews
and Meta-Analyses (PRISMA) [52] protocol was used
as a framework for this systematic review and meta-
analysis. The keywords used for systematic search in
the two databases PubMed and the Cochrane Library
up to August 2021 have been carefully specified in
Table 3 in the Appendix. There was also a hand search
on Google Scholar. The search language was limited
to articles published in English and those available
online.
Inclusion and exclusion criteria
The intervention variable in the current study was
any type of exercise training. The population selected
for the current study was patients with musculoskele-
tal pain. The outcome assessed for this study was
depression and anxiety. Randomized control trials
were eligible for this study. Cluster randomized con-
trol trials have been excluded from the present meta-
analysis [53, 54]. Eligible studies reported mean, stan-
dard deviation, and sample size in the post-test. Non-
randomized clinical trials were excluded from this
study. Studies with multiple simultaneous interven-
tions were also ineligible for inclusion in the current
meta-analysis. Studies that did not have a reference
group were also excluded from the meta-analysis.
K
 Table 1 Studies and their data
Reference Country Design Follow-up Age Sex Sample Exercise Depression and anxiety measure Musculoskeletal Reference Quality dimensions Results
% women size pain group N (Mean, standard
Selection bias PerformanceDetection Attrition Reporting
deviation)

K
bias bias bias bias
Random Allocation
sequence conceal-
generation ment
Ahmadizadeh Iran Single-blinded ran- 8-weeks Intervention Women 32 Stabilization Beck Depression Inventory-II Low back pain Control group Unclear Unclear High Low Low Low Depression
et al. (2020) [67] domized controlled 31.12 ± 8.29 exercises Higher score = higher depression Intervention
trial Control 16 (9.68 ± 5.92)
34.19 ± 8.36 Control
16 (14.31 ± 7.28)
Chatzitheodorou Greece Randomized control 12-weeks 25–65 45% 20 Exercise Hospital anxiety and depression scale Chronic low Control group Low Unclear Unclear Unclear Unclear Low Depression/anxiety
et al. (2007) [68] trial women training Higher score = higher depression, back pain Intervention
anxiety 10 (16.2 ± 3.4)
Control
10 (21.9 ± 4.5)
De Oliveira Brazil Individual Random- 5-weeks 30–59 73.7% 42 Therapeutic Beck Depression Inventory Chronic non- Osteopathic Low Low Low Low Low Low Depression
Meirelles et al. ized controlled trial women exercises Higher score = higher depression specific low manipulation Intervention
(2020) [69] back pain treatment 18 (10 ± 5)
Control
20 (6 ± 5)
Dusunceli et al. Turkey Single-blinded ran- 12- 18–55 72.2% 36 Stabilization Beck Depression Inventory Neck pain Physical Unclear Unclear High Low Low Low Depression
(2009) [70] domized controlled months women exercises Higher score = higher depression therapy Intervention
trial 19 (13.9 ± 9.5)
Control
17 (17.4 ± 4.8)
Harris et al. Norway Randomized con- 12- 20–60 50.5% 115 Physical Hospital anxiety and depression scale Chronic low Cognitive- Low Low Unclear Unclear Low Low Depression
(2017) [71] trolled trial months women group Higher score = higher depression, back pain behavioural Intervention
exercise anxiety treatments 60 (2.87 ± 3.16)
Control
55 (3.42 ± 3.27)
Anxiety
Intervention
60 (3.78 ± 3.74)
Control
55 (3.93 ± 4.05)
Jensen et al. Denmark Randomized con- 12- > 18 68% 96 Exercise Beck Depression Inventory Low back pain Rest Low Low High Low Low Low Depression
(2012) [72] trolled trial months women Higher score = higher depression Intervention
47 (8 ± 6.1)
Control
49 (9.5 ± 7.1)
Kuvačić et al. Italy Randomized con- 8-weeks 34.2 ± 4.52 46.7% 30 Yoga Zung Chronic low Pamphlet Unclear Unclear Unclear Unclear High Low Depression
(2018) [73] trolled trial women Questionnaire back pain Intervention
Higher score = higher depression, 15 (43.47 ± 2.85)
anxiety Control
15 (47.13 ± 1.60)
Anxiety
Intervention
15 (43.13 ± 1.85)
Control
15 (45.60 ± 1.76)

Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . .
review
 Table 1 (Continued)
Reference Country Design Follow-up Age Sex Sample Exercise Depression and anxiety measure Musculoskeletal Reference Quality dimensions Results
% women size pain group N (Mean, standard
Selection bias PerformanceDetection Attrition Reporting
deviation)
bias bias bias bias
Random Allocation
review

sequence conceal-
generation ment
Lauche et al. Germany Individual Random- 24-weeks 49.4 ± 11.7 79.8% 114 Tai Chi Hospital anxiety and depression scale Chronic non- Wait list Low Unclear High High Low Low Depression
(2016) [74] ized controlled trial women Higher score = higher depression, specific neck Intervention
anxiety pain 38 (4.1 ± 3.8)
Control
39 (5.4 ± 4.0)
Anxiety
Intervention
38 (6.1 ± 4.5)
Control
39 (6.7 ± 3.4)
Michalsen et al. Germany Randomized con- 8-weeks 18–75 75% 68 Exercise Hospital anxiety and depression scale Chronic low- Meditation Low Unclear High Low Low Low Depression
(2016) [75] trolled trial women Higher score = higher depression, back pain Intervention
anxiety 36 (7 ± 3.9)
Control
32 (7.5 ± 4.5)
Anxiety
Intervention
36 (8.3 ± 3.9)
Control
32 (8.8 ± 4.7)
Murtezani et al. Kosovo Randomized con- 12-weeks 18–65 48.5% 101 Exercise Hospital anxiety and depression scale Chronic low- Passive Low Low High High Low Low Depression/anxiety
(2011) [76] trolled trial women Higher score = higher depression, back pain modalities Intervention
anxiety 50 (14 ± 6.7)
Control
51 (21.1 ± 4.8)
O’Connor et al. USA Individual parallel- 12-weeks 17–38 Women 89 Resistance Profile of Mood States questionnaire Back pain Waiting list Low Low High Unclear Low Low Depression
(2018) [77] group randomized exercise Higher score = higher depression Exercise group
controlled trial 44 (1.50 ± 2.09)
Control Group
45 (2.07 ± 2.34)
Sertpoyraz et al. Turkey Individual Random- 1-month 20–45 77.5% 40 Isokinetic Beck Depression Inventory Chronic low Standard Low Unclear High Low Unclear Low Depression
(2009) [78] ized controlled trial women exercises Higher score = higher depression back pain exercise Intervention
20 (5.11 ± 4.90)
Control
20 (5.95 ± 7.37)
Shariat et al. Iran Single-blind random- 12-weeks 20–50 Unknown 72 Exercise Hospital anxiety and depression scale Chronic low Control group Unclear Unclear High Low Low Low Anxiety

Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . .
(2019) [79] ized controlled trial Higher score = higher depression, back pain Intervention
anxiety 19 (8 ± 1)
Control
17 (12 ± 2)

K
 Table 1 (Continued)
Reference Country Design Follow-up Age Sex Sample Exercise Depression and anxiety measure Musculoskeletal Reference Quality dimensions Results
% women size pain group N (Mean, standard
Selection bias PerformanceDetection Attrition Reporting
deviation)
bias bias bias bias

K
Random Allocation
sequence conceal-
generation ment
Sit et al. (2021) Hong Kong Randomized con- 12-weeks ≥ 65 93.1% 72 Neuro- The 9-item Patient Health Questionnaire Musculoskele- Control group Low Low High High Low Low Depression
[80] trolled trial women muscular 7-item tal pain Intervention
exercise Generalized Anxiety Disorder 36 (5.3 ± 4.9)
Higher score = higher depression, Control
anxiety 36 (5.7 ± 3.5)
Anxiety
Intervention
36 (4.3 ± 4.9)
Control
36 (4.5 ± 3.2)
Tekur et al. India Single-blind random- 7-day 18–60 45% 80 Yoga Beck’s depression inventory Chronic low Control group Low Low High Low Low Low Depression
(2012) [81] ized controlled trial women State-trait anxiety inventory back pain Intervention
Higher score = higher depression, 40 (6.43 ± 7.73)
anxiety Control
40 (10.45 ± 5.55)
a
Trait anxiety
Intervention
40 (36.32 ± 7.15)
Control
40 (43.25 ± 7.57)
Telles et al. India Randomized con- 12-weeks 20–45 57.5% 40 Yoga State-trait anxiety inventory Low back pain Control group Low Low High Low Low Low Anxiety
(2016) [82] trolled trial women Higher score = higher anxiety Intervention
20 (37.15 ± 8.68)
Control
20 (43.80 ± 10.88)
b
Teut et al. (2016) Germany Individual Random- 6-months ≥ 65 88.6% 176 Qigong Geriatric depression scale Chronic low Without Low Low Unclear High Low Low Depression
[83] ized controlled trial women Higher score = higher depression back pain intervention Intervention
58 (3.06 ± 1.97)
Control
57 (3.40 ± 3.05)
Von Trott et al. Germany Individual Random- 6-months 76 ± 8 95% 117 Qigong General scale Chronic Neck Control group Low Unclear High High Low Low Depression
(2009) [85] ized controlled trial women of depression Pain Intervention
Higher score = higher depression 38 (22.7 ± 7.4)
Control
40 (19.8 ± 9)
Uluğ et al. [84] Turkey Randomized con- 6-weeks 18–50 84.2% 56 Pilates Beck Depression Inventory Chronic neck Isometric Low Unclear High Low Low Low Depression
trolled trial women Higher score = higher depression pain Intervention
20 (8.5 ± 6.5)
Control
18 (9.7 ± 7.7)
ITT Intent-to-Treat analysis
aCalculated by author(s)
b
One treatment group, one scale or one time point was selected

Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . .
review
 review

Table 2 The effect of exercise training on depression and anxiety based on pain site
Number of studies Pain site Outcome Hedges’ g Lower limit Upper limit Z value P value
10 Low back pain Depression –0.26 –0.51 –0.01 2.06 0.039
4 Neck pain Depression –0.12 –0.49 0.26 0.61 0.542
6 Low back pain Anxiety –0.85 –1.46 –0.25 2.77 0.006

Among studies published from the same database Qualitative assessment

only one study with the highest quality was selected.
Some studies did not have clear results and were dis-
carded after the authors were contacted but did not
respond. In cases where there were several types of
exercise training interventions, only one type with the
highest quality was selected.
The Cochrane Collaboration [55] tool was used to as-
sess the quality of studies included in the meta-anal-
ysis of clinical trials. This tool measures five dimen-
sions of the quality of each study. These dimensions
are listed in Table 1.

Data extraction Statistical analysis

According to procedures in systematic review and
meta-analysis studies, a set of information was ex-
tracted from each manuscript, which is fully shown
in Table 1. This information included the names of
the authors, country, the follow-up period, the demo-
graphic information of the study population, measure
of depression and anxiety, and the effect size for each
study.
Recommended methods by the Cochrane Handbook
[56] were used for the meta-analysis of randomized
controlled trials. For each of the studies included
in the meta-analysis, the mean, standard deviation,
and sample size were extracted in the post-test, and
existing methods were used where calculations were
needed [56]. The effect size was calculated for each
of the randomized controlled trials. Effect sizes 0.20,
0.50, and 0.80 are classified as small, medium, and
large effect sizes [57]. To eliminate the effect of differ-
ent sample sizes, Hedges’ g was calculated [58] with

Fig. 1 Study selection di-

Identification

agram. (From: [52]. For

more information, visit Records idenfied through Addional records idenfied
www.prisma-statement.org) database searching through other sources
(n =7,858 ) (n = 0 )
Screening

Records aer duplicates removed

(n =7,467 )

Records excluded
(n = 6,879)
Records screened
(n = 7,467) Excluded based on
abstracts
Eligibility

Full-text arcles assessed Full-text arcles excluded, with

for eligibility reasons
(n =588) (n = 86)
Change score (n=2)
Lumbar spinal stenosis (n=1)
Studies included in Mixed intervenon (n=8)
qualitave synthesis Non-RCT (n=6)
(n = 105 ) Mixed intervenon (n=3)
Included

Inadequate result (n=10)

Review (n=53)
Studies with same database (n=3)
Studies included in
quantave synthesis
(meta-analysis)
(n = 19 )

Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . . K

a 95% confidence interval and P < 0.05. The studies
were pooled using the random-effects method. Then,
the degree of heterogeneity and publication bias in
the meta-analysis were examined. Q test and I2 [59,
60] were used for heterogeneity. Accordingly, the de-
gree of heterogeneity has three levels [61]. To check
the publication bias, first, the funnel plot was drawn
[62, 63], and then the Egger’s test was examined [64,
65], and finally, the missing studies were examined us-
ing the Trim and fill [66]. Stata-14 was used to analyse
the results (Stata Corp. College Station, TX, USA).
Results
Study selection
Studies were screened according to the PRISMA
flowchart in Fig. 1. Searching three databases based
on keywords retrieved 7858 manuscripts. In the next
step, the duplicate studies were deleted and then all
the studies were reviewed based on the abstract and
titles, and studies were evaluated based on the full
text. Finally, 105 manuscripts remained for the final
evaluation, of which 19 were eligible studies [67–85].
Fifteen studies were included in the meta-analysis for
Fig. 2 Frost plot of exercise training and depression
K Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . .
review
the effect of exercise on depression, and eight studies
were included in the meta-analysis for the effect of
exercise on anxiety. The total population included in
this meta-analysis was 1396 patients.
Quality of studies
Table 1 details the qualitative evaluation of studies
based on different dimensions of bias. In general, it
shows the moderate and high quality of the studies
included in the meta-analysis.
Exercise training and depression and anxiety
The effect of exercise training on depression in pa-
tients with musculoskeletal pain in Fig. 2 shows
that exercise reduces depression and Hedges’ g was
equal to –0.21, with confidence intervals –0.40, –0.02
(Z = 2.18; P = 0.029; I2 = 53.2%).
The effect of exercise training on anxiety in patients
with musculoskeletal pain in Fig. 3 shows that exercise
reduces anxiety and Hedges’ g was equal to –0.63, with
confidence intervals –1.08, –0.19 (Z = 2.77; P = 0.006;
I2 = 82.8%).
 review

Fig. 3 Frost plot of exercise training and anxiety

Two studies examined the effect of exercise on that there was no publication bias. Finally, the trim-
mixed anxiety/depression. Exercise training effects and-fill [66] showed that there were no missing study
on mixed anxiety/depression in patients with mus- in the meta-analysis of the effect of exercise on de-
culoskeletal pain shows that exercise reduces mixed pression in patients with musculoskeletal pain (Fig. 4).
anxiety/depression and Hedges’ g was equal to –1.24, Regarding the effect of exercise training on anxiety
with a confidence interval of –1.63, –0.84 (Z = 6.19; in patients with musculoskeletal pain, the Q test was
P < 0.001; I2 = 0%) (not reported in a Figure). equal to 40.79 (d.f 7; P < 0.001), I2 was 82.8%, which in-
The effect of exercise training on depression in pa- dicates a high level of heterogeneity [61]. Egger’s test
tients with low back pain in Table 2 shows that ex- (P = 0.010) was significant and showed that there was
ercise training reduces depression and Hedges’ g was publication bias. Finally, trim-and-fill [66] showed
equal to –0.26, with confidence intervals –0.51, –0.01 that there were no missing studies in the meta-analy-
(Z = 2.06; P = 0.039; I2 = 61.3%). The effect of exercise
training on depression in patients with neck pain (Ta-
ble 2) was non-significant and Hedges’ g was equal to
–0.12, with confidence intervals –0.49, –0.26 (Z = 0.61;
P = 0.542; I2 = 49.4%).
The effect of exercise training on anxiety in patients
with low back pain (Table 2) shows that exercise re-
duces anxiety and Hedges’ g was equal to –0.85, with
confidence intervals –1.46, –0.25 (Z = 2.77; P = 0.006;
I2 = 85.9%).

Publication bias

Regarding the effect of exercise training on depression

in patients with musculoskeletal pain, the Q test was
equal to 30.37 (d.f 14; P = 0.007), I2 was 53.9%, which
indicates a moderate level of heterogeneity [61]. Eg-
ger’s test (P = 0.378) was non-significant and showed Fig. 4 Funnel plot of exercise training and depression

Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . . K

Fig. 5 Funnel plot of exercise training and anxiety
sis of the effect of exercise on anxiety in patients with
musculoskeletal pain (Fig. 5).
Discussion
This study examined the effect of exercise training
on improving depression and anxiety in patients with
musculoskeletal pain. For this purpose, 19 random-
ized controlled trial studies were reviewed and meta-
analysed. The first finding is related to the effect of
exercise training on depression in patients with mus-
culoskeletal pain, which showed that exercise training
reduces depression. In other words, people who ex-
ercised experienced an improvement in depression.
This means that people with musculoskeletal pain
who exercise are in a better state of depression than
the reference group. This finding is consistent with
a meta-analytic study that examined the effect of
resistance exercise training on depression [86]. The
difference is that in the current study, the effect size
was small, but in the above meta-analysis [86], the ef-
fect size was reported to be medium. Also, in a similar
meta-analysis study that examined the effect of exer-
cise training on depression in patients with multiple
sclerosis [87], the results showed that exercise in these
patients also leads to improvement in depression, and
the effect size was small. According to the findings of
the current study and studies conducted in different
populations, it was found that exercise training is an
important factor in improving depression, especially
in patients with musculoskeletal pain. Therefore,
some mechanisms can explain the effect of exercise
training on improving depression. One mechanism in
this connection is the neural mechanisms that exist
in the relationship between exercise and the improve-
ment of depression [88]. It has been suggested that
both antidepressants and exercise might improve de-
pression through the same neuromolecular pathways
[89, 90]. This effect is accomplished by increasing
neurotrophic factors [89, 90], increased serotonin
neurotransmitter and norepinephrine [91], regulation
K Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . .
review
of the hypothalamic–pituitary–adrenal axis [92], and
other neural and physical pathways [88]. Another hy-
pothesis states that the reason for the improvement
in depression after exercise is an increase in body
temperature, which is known as the thermogenic hy-
pothesis [93]. Based on this hypothesis, it has been
stated that increasing the temperature of certain areas
of the brain and the brain stem leads to a feeling of
relaxation and a reduction in muscle tension [93].
Another finding of this study showed that exercise
training for anxiety in patients with musculoskeletal
pain has positive effects. The effect size obtained for
this finding was medium. A previous meta-analysis
study on adults also showed positive effects of exer-
cise on anxiety improvement, but the effect size of
the study was small [94]. Two new meta-analyses have
also found a positive finding that exercise training im-
proves anxiety, which also had a medium effect size
[95, 96]. A similar approach to depression has been
proposed on how exercise affects anxiety and given
that the effect size of exercise on anxiety was greater
than that on depression, this finding is consistent with
the thermogenic hypothesis, which states that exer-
cise only affects anxiety, not depression [93, 97, 98].
Another finding of the present study was that exercise
training improves depression and anxiety in patients
with low back pain and this finding was not signifi-
cant for neck pain. One reason for this finding could
be that only four studies on neck pain were included
and this could have influenced the results.
To our knowledge, this is the first study to meta-
analyse the effect of exercise training on depression
and anxiety in patients with musculoskeletal pain, and
no similar study has been reported in people with
musculoskeletal pain, although mental health prob-
lems are common in this population. The present
finding was evaluated separately for patients with low
back pain and neck pain, and depression and anxiety
were assessed separately. This study included ran-
domized controlled trials in a meta-analysis. The first
limitation was that not all types of musculoskeletal
pain had been studied in the original studies to date,
such as foot pain, shoulder pain, and so on. It was not
possible to distinguish between different types of ex-
ercise in this meta-analysis and this needs to be done
in future studies. Publication bias and heterogeneity
were other limitations, although in some subgroups,
the level of heterogeneity was moderate and there was
no publication bias. Heterogeneity has two clinical
and statistical origins and this heterogeneity is some-
what unavoidable in meta-analyses.
Clinical implications
According to the results of the current study, it can
be said that exercise (yoga, resistance exercise, isoki-
netic exercises, Qigong, Pilates, and Tai Chi) has posi-
tive effects on patients with musculoskeletal pain and
 review

therefore it is recommended that experts in this field

use these interventions more.
Funding None to declare.

Author Contribution S. Amiri: Contributed to the formation

of the subject, collecting and extracting data, analysing data
and writing.
Conflict of interest S. Amiri declares that he has no competing
interests.

Appendix

Table 3 Keywords used for PubMed, and the Cochrane Library until August 2021
Search Query
PubMed 3420
#1 Low back pain [Mesh] Low back pain[Text Word] OR Spinal diseases[Mesh] OR spinal diseases [Text Word] OR spinal pain [Text Word] OR back pain
[Mesh] OR back pain [Text Word] OR back disorders [Text Word] OR sciatica [Mesh] OR sciatica[Text Word] OR lumbar radicular pain [Text Word] OR
sciatic pain [Text Word] OR Lumbago [Text Word] OR Back Ache [Text Word] OR Neck Ache [Text Word] OR Neck pain [Mesh] OR Neck pain [Text
Word] OR Musculoskeletal Pain [Mesh] OR Musculoskeletal Pain [Text Word] OR shoulder pain [Mesh] OR shoulder pain [Text Word] OR Arm pain
[Text Word] OR Hand pain [Text Word] OR Foot pain [Text Word] OR Ankle pain [Text Word]
#2 Exercise [Mesh] OR Exercise [Text Word] OR Exercise therapy [Mesh] OR Exercise therapy [Text Word] OR Exercise Training [Text Word] OR exercise
program [Text Word] OR Running [Mesh] OR Running [Text Word] OR Jogging [Mesh] OR Jogging [Text Word] OR Exercise, Physical [Text Word] OR
Exercises [Text Word] OR Acute Exercises [Text Word] OR Aerobic Exercise [Text Word] OR Physical Activity [Text Word] OR Physical Exertion [Mesh]
OR Physical Exertion [Text Word] OR Activities, Physical [Text Word] OR Leisure time [Text Word] OR Activities, Leisure [Text Word] OR Leisure Activ-
ities [Mesh] OR Leisure Activities [Text Word] OR Leisure [Text Word] OR Human Activity [Mesh] OR Human Activity [Text Word] OR Walking [Mesh]
OR Walking [Text Word] OR Sports [Mesh] OR Sports [Text Word] OR Yoga [Mesh] OR Yoga [Text Word] OR Tai Ji [Mesh] OR Tai Ji [Text Word]
#3 Agoraphobia [Mesh] OR Agoraphobia [Text Word] OR Neurotic Disorders [Mesh] OR Neurotic Disorders [Text Word] OR Obsessive-Compulsive Dis-
order [Mesh] OR Obsessive-Compulsive Disorder [Text Word] OR Hoarding Disorder [Mesh] OR Hoarding Disorder [Text Word] OR Phobic Disorders
[Mesh] OR Phobic Disorders [Text Word] OR Social Phobia [Mesh] OR Social Phobia [Text Word] OR generalized anxiety disorder [Mesh] OR gener-
alized anxiety disorder [Text Word] OR post-traumatic stress disorder [Mesh] OR post-traumatic stress disorder [Text Word] OR phobia [Mesh] OR
phobia [Text Word] OR specific phobia [Mesh] OR specific phobia [Text Word] OR Panic Disorder [Mesh] OR Panic Disorder [Text Word] OR Obses-
sive-Compulsive [Mesh] OR Obsessive-Compulsive [Text Word] OR Neurosis [Mesh] OR Neurosis [Text Word] OR Obsessive-Compulsive Neurosis
[Mesh] OR Obsessive-Compulsive Neurosis [Text Word] OR GAD [Mesh] OR GAD [Text Word] OR PTSD [Mesh] OR PTSD [Text Word] OR fear [Mesh]
OR fear [Text Word] OR Panic [Mesh] OR panic [Text Word] OR anxiety [Mesh] OR anxiety [Text Word] OR Post-Traumatic [Mesh] OR Post Traumatic
[Text Word] OR mental disorders [Mesh] OR mental disorders [Text Word] OR Stress [Mesh] OR Stress [Text Word] OR psychiatric disorders [Mesh]
OR psychiatric disorders [Text Word] OR Mental illness [Mesh] OR Mental illness [Text Word] OR Depression [Mesh] OR Depression [Text Word] OR
Depressive Symptom [Text Word] OR Depressive Disorders [Mesh] OR Depressive Disorders [Text Word] OR Depressive Syndrome [Text Word] OR
Depressive Disorder, Major [Mesh] OR Depressive Disorder, Major [Text Word] OR Mood Disorders [Mesh] OR Mood Disorders [Text Word] OR Affec-
tive Disorders [Text Word]
Final #1 AND #2
The 4438
Cochrane
Library
#1 Exercise OR Exercise therapy OR Exercise Training OR Exercise program OR Running OR Jogging OR Exercises OR Acute Exercises OR Aerobic
Exercise OR Physical Activity OR Physical Exertion OR Physical Exertion OR Leisure time OR Leisure Activities OR Leisure OR Human Activity OR
Walking OR Sports OR Yoga OR Tai Ji
#2 Low back pain OR Spinal diseases OR spinal pain OR back pain OR back disorders OR sciatica OR lumbar radicular pain OR sciatic pain OR Lumbago
OR Back Ache OR Neck Ache OR Neck pain OR Musculoskeletal Pain OR shoulder pain OR Arm pain OR Hand pain OR Foot pain OR Ankle pain
#3 Agoraphobia OR Anxiety Separation OR Neurotic Disorders OR Obsessive-Compulsive Disorder OR Hoarding Disorder OR Phobic Disorders OR Social
Phobia OR generalized anxiety disorder OR post-traumatic stress disorder OR phobia OR specific phobia OR Panic Disorder OR Obsessive-Compul-
sive OR Neurosis OR Obsessive-Compulsive Neurosis OR GAD OR PTSD OR fear OR panic OR anxiety OR Post-Traumatic OR mental disorders OR
Stress OR psychiatric disorders OR Mental illness OR Depression OR Depressive Symptom OR Depressive Disorders OR Depressive Syndrome OR
Depressive Disorder, Major OR Mood Disorders OR Affective Disorders OR Mental Disorders OR Psychiatric disorders

Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . . K

References
1. CiezaA,CauseyK,KamenovK,HansonSW,ChatterjiS,VosT.
Global estimates of the need for rehabilitation based on the
Global Burden of Disease Study 2019: a systematic analysis
for the Global Burden of Disease Study 2019. Lancet.
2021;396(10267):2006–17.
2. Briggs AM, Cross MJ, Hoy DG, et al. Musculoskeletal health
conditions represent a global threat to healthy aging: A
report for the 2015 world health organization world report
on ageing and health. Gerontologist. 2016;56(Suppl
2):S243–55.
3. Briggs AM, Woolf AD, Dreinhöfer K, et al. Reducing the
global burden of musculoskeletal conditions. Bull World
Health Organ. 2018;96(5):366–8.
4. Hartvigsen J, Hancock MJ, Kongsted A, et al. What low
back pain is and why we need to pay attention. Lancet.
2018;391(10137):2356–67.
5. Safiri S, Kolahi A-A, Cross M, et al. Prevalence, deaths, and
disability-adjusted life years due to musculoskeletal disor-
ders for 195 countries and territories 1990–2017. Arthritis
Rheumatol. 2021;73(4):702–14.
6. Kyu HH, Abate D, Abate KH, et al. Global, regional,
and national disability-adjusted life-years (DALYs) for 359
diseases and injuries and healthy life expectancy (HALE)
for 195 countries and territories, 1990–2017: a systematic
analysis for the Global Burden of Disease Study 2017.
Lancet. 2018;392(10159):1859–922. https://doi.org/10.
1016/S0140-6736(18)32335-3.
7. James SL, Abate D, Abate KH, et al. Global, regional, and na-
tional incidence, prevalence, and years lived with disability
for 354 diseases and injuries for 195 countries and territo-
ries, 1990–2017: a systematic analysis for the Global Burden
of Disease Study 2017. Lancet. 2018;392(10159):1789–858.
https://doi.org/10.1016/S0140-6736(18)32279-7.
8. Williams A, Kamper SJ, Wiggers JH, et al. Musculoskeletal
conditions may increase the risk of chronic disease: a sys-
tematic review and meta-analysis of cohort studies. BMC
Med. 2018;16(1):167.
9. Oliveira CB, Maher CG, Franco MR, et al. Co-occurrence
of chronic musculoskeletal pain and cardiovascular dis-
eases: a systematic review with meta-analysis. Pain Med.
2020;21(6):1106–21.
10. Chen J, Zhang Y, Simonsick E, et al. Back pain and heart
failure in community-dwelling older adults: Findings from
the Health ABC study. Geriatr Nurs. 2021;42(3):643–9.
11. Roseen EJ, Rajendran I, Stein P, et al. Association of back
pain with mortality: a systematic review and meta-analysis
of cohort studies. J Gen Intern Med. 2021;36:3148–58.
12. Hannerz H, Holtermann A, Madsen IEH. Musculoskeletal
pain as a predictor for depression in the general working
population of Denmark. Scand J Public Health. 2020;
https://doi.org/10.1177/1403494819875337.
13. Amiri S, Behnezhad S, EJTIJoPiM A. Back pain and de-
pressive symptoms: A systematic review and meta-analy-
sis. Int J Psychiatry Med. 2020; https://doi.org/10.1177/
0091217420913001.
14. Fernandez M, Colodro-Conde L, Hartvigsen J, et al. Chronic
low back pain and the risk of depression or anxiety symp-
toms: insights from a longitudinal twin study. Spine J.
2017;17(7):905–12. https://doi.org/10.1016/j.spinee.2017.
02.009.
15. Robertson D, Kumbhare D, Nolet P, Srbely J, Newton G.
Associations between low back pain and depression and
somatization in a Canadian emerging adult population.
J Can Chiropr Assoc. 2017;61(2):96–105.
K Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . .
review
16. Sagheer MA, Khan MF, Sharif S. Association between
chronic low back pain, anxiety and depression in patients at
a tertiary care centre. J Pak Med Assoc. 2013;63(6):688–90.
17. Malhi GS, Mann JJ. Depression. Lancet. 2018;392(10161):
2299–312.
18. Waraich P, Goldner EM, Somers JM, Hsu L. Prevalence and
incidence studies of mood disorders: a systematic review of
the literature. Can J Psychiatry. 2004;49(2):124–38.
19. Bromet E, Andrade LH, Hwang I, et al. Cross-national
epidemiology of DSM-IV major depressive episode. BMC
Med. 2011;9:90.
20. Malhi GS, Outhred T, Hamilton A, et al. Royal Australian
and New Zealand College of Psychiatrists clinical practice
guidelines for mood disorders: major depression summary.
Med J Aust. 2018;208(4):175–80.
21. Kessler RC, Bromet EJ. The epidemiology of depression
across cultures. Annu Rev Public Health. 2013;34:119–38.
22. Hirschfeld RM. The epidemiology of depression and the
evolution of treatment. J Clin Psychiatry. 2012;73(Suppl
1):5–9.
23. Moffitt TE, Caspi A, Taylor A, et al. How common are
common mental disorders? Evidence that lifetime preva-
lence rates are doubled by prospective versus retrospective
ascertainment. Psychol Med. 2010;40(6):899–909.
24. WorldHealthOrganization. Depressionandothercommon
mental disorders: global health estimates. 2017.
25. World Health Organization. The global burden of disease:
2004 update. 2008.
26. Vos T, Abajobir AA, Abate KH, et al. Global, regional,
and national incidence, prevalence, and years lived with
disability for 328 diseases and injuries for 195 countries,
1990–2016: a systematic analysis for the Global Burden of
Disease Study 2016. Lancet. 2017;390(10100):1211–59.
https://doi.org/10.1016/S0140-6736(17)32154-2.
27. Penninx BWJH, Pine DS, Holmes EA, Reif A. Anxiety disor-
ders. Lancet. 2021;397(10277):914–27.
28. Gustavsson A, Svensson M, Jacobi F, et al. Cost of disorders
of the brain in Europe 2010. Eur Neuropsychopharmacol.
2011;21(10):718–79. https://doi.org/10.1016/j.euroneuro.
2011.08.008.
29. Kvam S, Kleppe CL, Nordhus IH, Hovland A. Exercise as
a treatment for depression: a meta-analysis. J Affect Disord.
2016;202:67–86.
30. Long BC, Van Stavel R. Effectsof exercisetraining on anxiety:
A meta-analysis. J Appl Sport Psychol. 1995;7(2):167–89.
31. Schuch FB, Vancampfort D, Richards J, Rosenbaum S,
Ward PB, Stubbs B. Exercise as a treatment for depression:
a meta-analysis adjusting for publication bias. J Psychiatr
Res. 2016;77:42–51.
32. Hayden JA, Van Tulder MW, Tomlinson G. Systematic re-
view: strategies for using exercise therapy to improve
outcomes in chronic low back pain. Ann Intern Med.
2005;142(9):776–85.
33. Searle A, Spink M, Ho A, Chuter V. Exercise interventions for
the treatment of chronic low back pain: a systematic review
and meta-analysis of randomised controlled trials. Clin
Rehabil. 2015;29(12):1155–67.
34. Van Middelkoop M, Rubinstein SM, Verhagen AP, et al.
Exercise therapy for chronic nonspecific low-back pain.
BestPractResClinRheumatol. 2010;24(2):193–204. https://
doi.org/10.1016/j.berh.2010.01.002.
35. Lim ECW, Poh RLC, Low AY, Wong WP. Effects of Pi-
lates-based exercises on pain and disability in individuals
with persistent nonspecific low back pain: a systematic
review with meta-analysis. J Orthop Sports Phys Ther.
2011;41(2):70–80.
 review
36. Owen PJ, Miller CT, Mundell NL, et al. Which specific
modes of exercise training are most effective for treating
low back pain? Network meta-analysis. Br J Sports Med.
2020;54(21):1279–87.
37. Ostman C, Smart NA, Morcos D, Duller A, Ridley W, Jewiss D.
The effect of exercise training on clinical outcomes in
patients with the metabolic syndrome: a systematic review
and meta-analysis. Cardiovasc Diabetol. 2017;16(1):110.
38. D-c L, Pate RR, Lavie CJ, Sui X, Church TS, Blair SN.
Leisure-time running reduces all-cause and cardiovascular
mortality risk. J Am Coll Cardiol. 2014;64(5):472–81.
39. Moore SC, Patel AV, Matthews CE, et al. Leisure time
physical activity of moderate to vigorous intensity and
mortality: a large pooled cohort analysis. PLoS Med.
2012;9(11):e1001335. https://doi.org/10.1371/journal.
pmed.1001335.
40. Iftikhar IH, Kline CE, Youngstedt SD. Effects of exer-
cise training on sleep apnea: a meta-analysis. Lung.
2014;192(1):175–84.
41. Aiello KD, Caughey WG, Nelluri B, Sharma A, Mookadam F,
Mookadam M. Effect of exercise training on sleep ap-
nea: a systematic review and meta-analysis. Respir Med.
2016;116:85–92.
42. Amiri S, Hasani J, Satkin M. Effect of exercise training on
improving sleep disturbances: a systematic review and
meta-analysis of randomized control trials. Sleep Med.
2021;84:205–18.
43. Piepoli MF, Davos C, Francis DP, Coats AJ. Exercise training
meta-analysis of trials in patients with chronic heart failure
(ExTraMATCH). BMJ. 2004;328(7433):189.
44. Gordon BR, McDowell CP, Hallgren M, Meyer JD, Lyons M,
Herring MP. Association of efficacy of resistance exer-
cise training with depressive symptoms: meta-analysis
and meta-regression analysis of randomized clinical trials.
JAMA Psychiatry. 2018;75(6):566–76.
45. Ensari I, Motl RW, Pilutti LA. Exercise training improves de-
pressivesymptomsinpeoplewithmultiplesclerosis: results
of a meta-analysis. J Psychosom Res. 2014;76(6):465–71.
46. 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. Arch Intern Med.
2012;172(2):101–11.
47. Gordon BR, McDowell CP, Lyons M, Herring MP. The effects
of resistance exercise training on anxiety: a meta-analysis
and meta-regression analysis of randomized controlled
trials. Sports Med. 2017;47(12):2521–32.
48. HerringMP,O’ConnorPJ,DishmanRK.Theeffectofexercise
training on anxiety symptoms among patients: asystematic
review. Arch Intern Med. 2010;170(4):321–31.
49. Mcdowell CP, Cook DB, Herring MP. The effects of exer-
cise training on anxiety in fibromyalgia patients: a meta-
analysis. Med Sci Sports Exerc. 2017;49(9):1868–76.
50. Mitchell AJ, Chan M, Bhatti H, et al. Prevalence of de-
pression, anxiety, and adjustment disorder in oncologi-
cal, haematological, and palliative-care settings: a meta-
analysis of 94 interview-based studies. Lancet Oncol.
2011;12(2):160–74.
51. Alonso J, Liu Z, Evans-Lacko S, et al. Treatment gap for
anxiety disorders is global: Results of the World Men-
tal Health Surveys in 21 countries. Depress Anxiety.
2018;35(3):195–208. https://doi.org/10.1002/da.22711.
52. Moher D, Liberati A, Tetzlaff J, Altman DG, ThePG. Preferred
reporting items for systematic reviews and meta-analyses:
the PRISMA statement. PLoS Med. 2009;6(7):e1000097.
https://doi.org/10.1371/journal.pmed1000097.
Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . .
53. Hedges LV. Effect sizes in cluster-randomized designs.
J Educ Behav Stat. 2007;32(4):341–70.
54. Higgins JP, et al. Cochrane handbook for systematic reviews
ofinterventionsversion5.0. 1. TheCochraneCollaboration;
2008.
55. Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane
Collaboration’s tool for assessing risk of bias in randomised
trials. 2011;343. https://doi.org/10.1136/bmj.d5928.
56. Higgins JP, Thomas J, Chandler J, et al. Cochrane handbook
for systematic reviews of interventions. John Wiley & Sons;
2019.
57. Cohen J. Statistical power analysis for the behavioral sci-
ences. New York: Academic Press; 2013.
58. Hedges L, Olkin I. Statistical methods in meta-analysis. Vol.
20. 1985.
59. Higgins JP, Thompson SG. Quantifying heterogeneity in
a meta-analysis. Stat Med. 2002;21(11):1539–58.
60. Ioannidis JP, Patsopoulos NA, Evangelou E. Uncertainty
in heterogeneity estimates in meta-analyses. BMJ.
2007;335(7626):914–6.
61. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring
inconsistency in meta-analyses. BMJ. 2003;327(7414):
557–60.
62. Rothstein HR, Sutton AJ, Borenstein M. Publication bias in
meta-analysis. 2005. pp. 1–7.
63. Borenstein M, Hedges LV, Higgins JP, Rothstein HR. Intro-
duction to meta-analysis. John Wiley & Sons; 2011.
64. Begg CB, Mazumdar M. Operating characteristics of
a rank correlation test for publication bias. Biometrics.
1994;50:1088–101.
65. Egger M, Smith GD, Schneider M, Minder CJB. Bias in
meta-analysis detected by a simple, graphical test. BMJ.
1997;315(7109):629–34.
66. Duval S, Tweedie R. Trim and fill: A simple funnel-plot-
based method of testing and adjusting for publication bias
in meta-analysis. Biometrics. 2000;56(2):455–63.
67. Ahmadizadeh Z, Ehsani F, Samaei SA, Mirmohammad-
khani M. Theeffectof stabilization exercises along withself-
care training on transverse abdominal activity, pain, and
disability in mothers with low back pain having children
with cerebral palsy: a randomized controlled trial. Am J
Phys Med Rehabil. 2020;99(2):156–60.
68. Chatzitheodorou D, Kabitsis C, Malliou P, Mougios V. A pilot
study of the effects of high-intensity aerobic exercise versus
passive interventions on pain, disability, psychological
strain, and serum cortisol concentrations in people with
chronic low back pain. Phys Ther. 2007;87(3):304–12.
69. de Oliveira Meirelles F, de Oliveira Muniz Cunha JC, da
Silva EB. Osteopathic manipulation treatment versus ther-
apeutic exercises in patients with chronic nonspecific low
back pain: a randomized, controlled and double-blind
study. J Back Musculoskelet Rehabil. 2020;33(3):367–77.
70. Dusunceli Y, OzturkC, Atamaz F, Hepguler S, Durmaz B. Effi-
cacy of neckstabilization exercisesfor neckpain: arandom-
ized controlled study. J Rehabil Med. 2009;41(8):626–31.
71. Harris A, Moe TF, Eriksen HR, et al. Brief intervention,
physical exercise and cognitive behavioural group therapy
for patients with chronic low back pain (The CINS trial). Eur
J Pain. 2017;21(8):1397–407.
72. Jensen RK, Leboeuf-Yde C, Wedderkopp N, Sorensen JS,
Manniche C. Rest versus exercise as treatment for patients
with low back pain and modic changes. A randomized
controlled clinical trial. BMCMed. 2012;10(1):1–13.
73. Kuvačić G, Fratini P, Padulo J, Antonio DI, De Giorgio A.
Effectiveness of yoga and educational intervention on dis-
ability, anxiety, depression, and pain in people with CLBP: A
K

randomized controlled trial. Complement Ther Clin Pract.
2018;31:262–7.
74. Lauche R, Stumpe C, Fehr J, et al. The effects of tai chi
and neck exercises in the treatment of chronic nonspe-
cific neck pain: a randomized controlled trial. J Pain.
2016;17(9):1013–27.
75. Michalsen A, Kunz N, Jeitler M, et al. Effectiveness of
focused meditation for patients with chronic low back
pain—A randomized controlled clinical trial. Complement
Ther Med. 2016;26:79–84.
76. Murtezani A, Hundozi H, Orovcanec N, Sllamniku S, Os-
mani T. A comparison of high intensity aerobic exercise and
passivemodalitiesforthetreatmentofworkerswithchronic
low back pain: a randomized, controlled trial. Eur J Phys
Rehabil Med. 2011;47(3):359–66.
77. O’Connor PJ, Poudevigne MS, Johnson KE, de Araujo JB,
Ward-Ritacco CL. Effects of resistance training on fatigue-
related domains of quality of life and mood during preg-
nancy: A randomized trial in pregnant women with back
pain. Psychosom Med. 2018;80(3):327.
78. Sertpoyraz F, Eyigor S, Karapolat H, Capaci K, Kirazli Y.
Comparison of isokinetic exercise versus standard exercise
training in patients with chronic low back pain: a random-
ized controlled study. Clin Rehabil. 2009;23(3):238–47.
79. ShariatA, Alizadeh R, Moradi V, etal. Theimpactof modified
exercise and relaxation therapy on chronic lower back pain
in office workers: a randomized clinical trial. J Exerc
Rehabil. 2019;15(5):703.
80. Sit RWS, Choi SYK, Wang B, et al. Neuromuscular exercise
for chronic musculoskeletal pain in older people: a ran-
domised controlled trial in primary care in Hong Kong. Br J
Gen Pract. 2021;71(704):e226–e36.
81. Tekur P, Nagarathna R, Chametcha S, Hankey A, Nagen-
dra H. A comprehensive yoga programs improves pain,
anxiety and depression in chronic low back pain patients
more than exercise: an RCT. Complement Ther Med.
2012;20(3):107–18.
82. TellesS,BhardwajAK,GuptaRK,SharmaSK,MonroR,Balkr-
ishna A. A randomized controlled trial to assess pain and
magnetic resonance imaging-based (MRI-Based) struc-
tural spine changes in low back pain patients after yoga
practice. Med Sci Monit. 2016;22:3238.
83. Teut M, Knilli J, Daus D, Roll S, Witt CM. Qigong or
yoga versus no intervention in older adults with chronic
low back pain—A randomized controlled trial. J Pain.
2016;17(7):796–805.
84. Uluğ N, Yilmaz ÖT, Kara M. Effects of pilates and yoga
in patients with chronic neck pain: A sonographic study.
J Rehabil Med. 2018;50(1):80–5.
85. von Trott P, Wiedemann AM, Lüdtke R, Reißhauer A,
Willich SN, Witt CM. Qigong and exercise therapy for elderly
K Exercise training and depression and anxiety in musculoskeletal pain patients: a meta-analysis of. . .
review
patients with chronic neck pain (QIBANE): a randomized
controlled study. J Pain. 2009;10(5):501–8.
86. Gordon BR, McDowell CP, Hallgren M, Meyer JD, Lyons M,
Herring MP. Association of efficacy of resistance exer-
cise training with depressive symptoms: meta-analysis
and meta-regression analysis of randomized clinical trials.
JAMApsychiatry. 2018;75(6):566–76.
87. Ensari I, Motl RW, Pilutti LA. Exercise training improves
depressive symptoms in people with multiple sclero-
sis: Results of a meta-analysis. J Psychosom Res.
2014;76(6):465–71.
88. Gujral S, Aizenstein H, Reynolds CF 3rd, Butters MA, Er-
ickson KI. Exercise effects on depression: Possible neural
mechanisms. Gen Hosp Psychiatry. 2017;49:2–10.
89. Russo-Neustadt AA, Beard RC, Huang YM, Cotman CW.
Physical activity and antidepressant treatment potentiate
the expression of specific brain-derived neurotrophic fac-
tor transcripts in the rat hippocampus. Neuroscience.
2000;101(2):305–12.
90. Garza AA, Ha TG, Garcia C, Chen MJ, Russo-Neustadt AA.
Exercise, antidepressant treatment, and BDNF mRNA ex-
pression in the aging brain. Pharmacol Biochem Behav.
2004;77(2):209–20.
91. Lin TW, Kuo YM. Exercise benefits brain function: the
monoamine connection. Brain Sci. 2013;3(1):39–53.
92. 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.
93. deVries HA. Tranquilizer effect of exercise: a critical review.
Phy Sportsmed. 1981;9(11):46–55.
94. Long BC, van Stavel R. Effectsof exercisetraining on anxiety:
A meta-analysis. J Appl Sport Psychol. 1995;7(2):167–89.
95. Gordon BR, McDowell CP, Lyons M, Herring MP. The effects
of resistance exercise training on anxiety: a meta-analysis
and meta-regression analysis of randomized controlled
trials. Sports Med. 2017;47(12):2521–32.
96. HerringMP,O’ConnorPJ,DishmanRK.Theeffectofexercise
trainingonanxietysymptomsamongpatients: Asystematic
review. Arch Intern Med. 2010;170(4):321–31.
97. Morgan WP, Goldston SE. Exercise and mental health.
Abingdon: Taylor & Francis; 2013.
98. Raglin JS, Morgan WP. Influence of exercise and quiet rest
on state anxiety and blood pressure. Med Sci Sports Exerc.
1987;19(5):456–63.
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