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SJP0010.1177/1403494819875337Hannerz et al.Musculoskeletal complaints and depression

Scandinavian Journal of Public Health,

1–9

ORIGINAL ARTICLE

Musculoskeletal pain as a predictor for depression in the general

working population of Denmark

HArAlD HAnnErz , AnDrEAS HOlTErMAnn &

IDA ElISAbETH HUITFElDT MADSEn

National Research Centre for the Working Environment, Denmark

Abstract

Aim:

This study examines the association between musculoskeletal complaints and subsequent use of antidepressants and/or

psychiatric hospital treatment for depressive mood disorders in the Danish labour force.

Methods:

The study is based on two

cohorts.The first cohort is the total labour force in 21 Danish municipalities (n=693,860), where the risk of depression (psychiatric

diagnosis or antidepressant treatment) during 2010–2015 was compared between individuals on long-term sickness absence

due to musculoskeletal disorders (MSD) and non-sick-listed gainfully employed individuals. The second cohort is a random

sample of the Danish labour force (n=9248) who were followed during 2011–2015 to estimate the association between self-rated

musculoskeletal pain and depression. All analyses were controlled for age, sex, calendar period and socio-economic status.

Results:

Compared to non-sick-listed gainfully employed individuals, there was an increased risk of depression in individuals sick-listed

with MSD, with rate ratios of 2.39 (99% confidence interval (CI) 2.22–2.58) for individuals with less severe MSD and 4.27 (99%

CI 3.98–4.59) for individuals with more severe MSD.There was also an increased risk of depression associated with self-rated pain

(yes vs. no), with a rate ratio of 2.17 (99% CI 1.69–2.78). The population attributable fraction of depression from musculoskeletal

pain was 0.35 (99% CI 0.24–0.45).

Conclusions:

The results of the present study indicate that musculoskeletal pain is

an important predictor of indicators of depression in the general working population of Denmark.

Keywords:

Blinded statistical analysis, musculoskeletal pain, depression, antidepressants, psychiatric hospital treatment, cohort study

Introduction

Approximately 25% of the working population in the

EU suffer from musculoskeletal disorders (MSD).

MSD are, by themselves, major contributors to the

global burden of disability [1]. Furthermore, it has

been hypothesised that they also may play an impor-

tant role in the development of major depression [2],

which is the second leading cause of disability world-

wide [1].

Musculoskeletal pain has been associated with

reduced physical activity [3,4] and disturbed sleep

[5], which in turn have been associated with increased

rates of depression [6,7]. Since MSD may play an

important role in the development of depression, it is

reasonable to believe that MSD may be an important

predictor of depression among people in the general

working population.

Several prospective studies have reported strong

associations between MSD and the development of

depressive symptoms [8–10]. The strong prospective

association between MSD and depression has, how-

ever, never been confirmed in a study with a pre-

published study protocol, in which all inclusion

criteria, statistical models, hypotheses and test crite-

ria are completely defined before the exposure data

of the study are linked to the outcome data. The pre-

sent study is based on a detailed protocol [11], which

was written and published before we obtained access

to the outcome data of the study.

Correspondence: Harald Hannerz, national research Centre for the Working Environment, lersø Parkallé 105, Kobenhavn, 2100, Denmark.

E-mail: [email protected]

Date received 1 May 2019; reviewed 11 July 2019; accepted 6 August 2019

Article reuse guidelines: sagepub.com/journals-permissions

https://doi.org/10.1177/1403494819875337

DOI: 10.1177/1403494819875337

journals.sagepub.com/home/sjp

BEU, Alm.del - 2019-20 - Bilag 213: Orientering om resultater fra NFA-artikel om sygemelding med muskelskeletbesvær, smerter og øget risiko for depression og/eller antidepressiv behandling, fra beskæftigelsesministeren

Hannerz et al.

and depression would also hold in a general working

population of non-sick-listed individuals. All analyses

were controlled for age, sex, socio-economic status

(SES) and calendar period.

Methods

The methodological details of the study were given in

our study protocol [11] and are repeated in the pre-

sent method section.

Study populations

The study population of the first and second parts of

the project consisted of people from the Danish

labour force who fulfilled the following criteria on 1

January 2010: were employed, self-employed, assist-

ing spouses or recipients of unemployment benefits;

were between 25 and 64 years old; had their residence

in any of 21 Danish municipalities that participated in

the Danish return-to-work program [13]; and did

not emigrate or immigrate, did not redeem any pre-

scription for antidepressant drugs and did not receive

hospital treatment for a mood disorder (ICD-10:

F30-F39) between 1 January 2005 and 31 January

2010/26 April 2010 for the first and second parts of

the study, respectively. residents who received sick-

ness benefits due to MSD sometime during the time

period February 2010–September 2012 were the

subjects of interest. The rest of the study population

served as a comparison group (standard population).

Our decision to consider only sickness absence in the

time period February 2010–September 2012 was due

to the lack of data about sickness absence episodes

outside of this time interval.

The third part of the project was based on people

who participated in a survey on working environment

and health that was conducted on a random sample

of the Danish population in 2010 [12]. This part of

the project included all participants who, on 1

January 2011, had their residence in Denmark and

fulfilled the previously mentioned criteria for SES

and age. It was, moreover, required that they did not

emigrate or immigrate, that they did not redeem any

prescription for antidepressant drugs and that they

did not receive hospital treatment for a mood disor-

der between 1 January 2006 and 31 December 2010.

Information about self-rated musculoskeletal pain

was retrieved from the survey data. Information

about MSD-related sickness absence was retrieved

from data registered at municipal sickness benefit

offices. Information about medicines, psychiatric

hospital treatments, age, sex, deaths, migrations,

employment and SES was retrieved from national

registers.

The study analyses data from two separate sur-

veys: (a) the Danish national Work Environment

Cohort Study, which collected data on health and

occupational exposures in a random sample of the

working population of Denmark in 2010 [12], and

(b) a survey of individuals on long-term sickness

benefit from 21 Danish municipalities, recruited in

2010–2012 for the Danish return-to-work project,

which was designed to evaluate a program to enhance

probabilities and rates of return to work among peo-

ple on sickness benefits [13]. The exposure data

obtained from these sources were linked to national

registers on redeemed prescribed medications and

psychiatric hospital treatments.

The first part of the present project aimed to esti-

mate the prospective association between long-term

sickness absence due to MSD and incident use of

prescribed antidepressants and/or psychiatric hospital

treatment due to a depressive mood disorder among

people in the Danish labour force. The following end

points were applied: (a) redeemed prescription for

antidepressant drugs (ATC-code n06A); (b) psychi-

atric hospital treatment with a depressive mood disor-

der (ICD-10: F32–F33) as principal diagnosis; and

psychiatric hospital treatment with a depressive mood

disorder as principal diagnosis.

The second part of the project aimed to test the

hypothesis of a positive dose–response relationship.

The hypothesis was that a more severe episode of

MSD-related sickness absence is associated with a

higher risk than exposure to a less severe episode,

which in turn is associated with a higher risk than

that of the general working population.

The third part of the project aimed to estimate the

prospective association between self-rated musculo-

skeletal pain in the neck, shoulders, elbow, forearm,

hand or lower back and incident use of prescribed

antidepressants and/or psychiatric hospital treatment

due to a depressive mood disorder in a random sam-

ple of the Danish labour force.

The study population of the first and second part

of the project was large enough to allow us to esti-

mate the prospective association between long-term

sickness absence due to MSD and psychiatric hospi-

tal diagnoses of depression. The results could thereby

tell us if a hypothetical association with antidepres-

sant drug use would also hold good when the

outcome is based on psychiatric hospital diagnoses

and vice versa. The results could not, however, tell us

to what extent the association was due to musculo-

skeletal pain or other adverse effects of being on

long-term sick leave. Hence, the third part of the

project was needed to verify that a hypothetical pro-

spective association between musculoskeletal pain

Musculoskeletal complaints and depression

Data registered at sickness benefit offices

The public sickness benefit scheme in Denmark covers

long-term sickness absence (>21 days in 2010–2011;

>30

days in 2012) among assisting spouses and self-

employed, employed and unemployed residents. The

system is administered by municipal sickness benefit

offices, which according to the Sickness benefits Act

are committed to follow up and continuously evaluate

each sick-listed person’s prognosis of returning to the

labour force [14]. In connection with the Danish

return-to-work program, which ran from February

2010 to September 2012, data were collected from

sickness benefit offices in 21 (out of 98) Danish munic-

ipalities. The obtained database contains inter alia the

cause of the sickness absence, the date of the first con-

sultation with the sickness benefit office and a personal

identification number, which enable linkage to data in

national registers. From 26 April 2010, it also contains

a variable which denotes the estimated severity of the

sickness absence episode. At the first consultation with

the sickness benefit office, the sick-listed person was

classified into one of the following severity categories:

(a) likely to return to the labour force within three

months, (b) unlikely to return to the labour force

within three months but able to participate in activities

aimed at facilitating a return, or (c) unlikely to return

to the labour force within three months and unable to

participate in activities [15].

Data from national registers

The project utilised data from the central person reg-

ister, the employment classification module, the psy-

chiatric central research register and the national

prescription register. The central person register con-

tains information on sex, addresses and dates of

birth, death and migrations for every person who is

or has been an inhabitant of Denmark sometime

between 1968 and the present time. A person’s SES,

occupation and industry have been registered annu-

ally in the employment classification module since

1975. The psychiatric central research register has

existed as a national register since 1970 and contains

data from all psychiatric hospital departments in

Denmark. From 1970 to 1994, the register only

included inpatients, but since 1995, it has also cov-

ered outpatients and emergency ward visits. Since

1994, the diagnoses are coded according to the

International Classification of Diseases, 10th revi-

sion (ICD-10) [16]. The national prescription regis-

ter covers all redeemed prescriptions at pharmacies

in Denmark since 1995, and the products are coded

in accordance with the Anatomical Therapeutic

Chemical (ATC) Classification System.

Data from the national survey

In the autumn of 2010, a random sample of 20- to

69-year-old residents of Denmark (n=30,000) were

invited to participate in a survey on working environ-

ment and health. Data were collected via a mailed

questionnaire, which contained 62 questions. The

response rate was 48%. Approximately 10,600 of the

respondents were either employed or self-employed

at the time of the interview [12].

Exposure categories in the first and second part

of the project

In the first part of the project, we operated with two

groups: (a) the standard population and (b) people

who (according to the data that were collected at the

sickness benefit offices) received sickness benefit due

to a MSD sometime between February 2010 and

September 2012.

The second part of the project operated with three

groups: (a) the standard population; (b) people who,

at their first consultation with the sickness benefit

office, were evaluated as likely to return to the labour

force within three months; and (c) people who were

evaluated as unlikely to return to the labour force

within three months.

At the start of the follow-up, everyone belonged to

the standard population. The ones who received sick-

ness benefit for MSD were shifted to groups 2/3 at

the date of their first consultation with the sickness

benefit office, wherein they remained throughout the

rest of the follow-up period.

Exposure categories in the third part of the

project

The participants in the national survey were asked to

rate their average pain during the last three months

in the neck/shoulders, elbow/forearm/hand and lower

back, respectively, on an integer grading scale from 0

to 9, where 0=no pain and 9 represents the worst

imaginable pain. The body regions were defined by

illustrative drawings.

In keeping with Andersen et al. [17], participants

who rated their pain as

⩾4

in any of the three body

regions were defined as exposed to musculoskeletal pain

(in the neck, shoulders, elbow, forearm, hand or lower

back), while the rest of the participants were defined as

unexposed. On a continuous 0–10 visual analogue scale,

it has been proposed that

�½3.4

should be interpreted as

mild pain, 3.5–7.4 as moderate pain and

⩾7.5

as severe

pain [18]. In keeping with this interpretation, a rating of

⩾4

on the scale in the present study may be interpreted

as exposed to moderate or severe pain.

Hannerz et al.

periods and clinical end points given in Table I were

estimated with 99% confidence intervals.

In the first and second parts of the project, long-

term sickness absence due to MSD was treated as a

time-varying variable. The study participants

belonged to the standard population until the date of

their first MSD-related consultation with the sick-

ness benefit office, at which time they were shifted

from the standard population to the MSD group,

wherein they remained throughout the rest of the

follow-up period. If the clinical end point of the study

occurred between the start of the follow-up and the

date of the first MSD-related consultation with the

sickness benefit office, then the case was counted as

having occurred in the standard population. Our

decision to end the follow-up when the clinical end

point of the study occurred ascertained that the

MSD-related sick absence was present before the

clinical end point among all cases that were counted

as having occurred in the MSD group.

Statistical significance criteria

In the first and third parts of the project, we regarded

an estimated rate ratio as statistically significant if its

99% confidence interval did not contain 1.

In the second part of the project, we regarded the

dose–response hypothesis as confirmed if:



log



−

3,1



log



1,0

 







  >

−

0.9

Min



( )





−

3,1

1,0





where

−

3,1

is the estimated rate ratio for severity

category 2–3 (unlikely to return to the labour force

within three months) versus severity category 1

(likely to return to the labour force within three

months),

1, 0

is the estimated rate ratio for severity

category 1 versus the standard population, the

SEs

are the standard errors of the logarithm of the esti-

mated rate ratios and

is the standard normal dis-

tribution function.

Population attributable fraction

In the third part of the project, we estimated the pop-

ulation attributable fraction (PAF) of depression

from musculoskeletal pain among economically

active people in Denmark in accordance with the

equation:

PAF

(

−

)



(

−

)







where p is the prevalence of musculoskeletal pain in

the neck, shoulders, elbow, forearm, hand or lower

Follow-up

The follow-up started on 1 February 2010, 26 April

2010 and 1 January 2011 in the first, second and

third parts of the project, respectively. The follow-up

ended at the time the participant reached the clinical

end point of the study, emigrated, died or the study

period ended (31 December 2015), whichever came

first. The reason for the different starting points of

the follow-up in the first and second parts of the pro-

ject (1 February and 26 April) was that the second

part of the project required information on the sever-

ity of the sickness absence episode, and this informa-

tion was not available in the period prior to 26 April

2010.

Clinical end points

The primary end point of a follow-up was reached if

and when the participant either redeemed a prescrip-

tion for antidepressant drugs (ATC-code n06A) or

received psychiatric hospital treatment for a depres-

sive mood disorder (ICD-10: F32–F33) as a princi-

pal diagnosis. We performed, however, a couple of

sensitivity analyses in the first part of the project in

which each of the components of the primary end

point was treated separately, that is, one of the sensi-

tivity analyses regarded a redeemed prescription for

antidepressant drugs (ATC-code n06A) as the end

point, while the other regarded psychiatric hospital

treatment with a principal diagnosis of depressive

mood disorder (ICD-10: F32–F33) as the end point.

Statistical analysis

We used Poisson regression to estimate the effect of

long-term sickness absence due to MSD and self-

rated musculoskeletal pain separately on the inci-

dence of redeemed prescriptions for antidepressant

drugs and/or hospital treatment due to a depressive

mood disorder. The analyses were controlled for sex,

age (five-year classes), calendar period (2010, 2011,

2012, 2013–2015) and SES (unemployed people;

self-employed people and assisting spouses; legisla-

tors, senior officials and managers; professionals;

technicians and associate professionals; workers in

occupations that require skills at a basic level; work-

ers in elementary occupations; gainfully occupied

people with an unknown occupation). Calendar

period were treated as a dynamic (time-varying) vari-

able. The remaining control variables were fixed at

baseline (1 January 2010 in the first and second parts

of the project, and 1 January 2011 in the third part).

The logarithm of person-years at risk was used as off-

set. rate ratios for the comparisons, follow-up

Musculoskeletal complaints and depression

Table I. Group comparisons, follow-up periods and clinical end points for which rate ratios were to be estimated according to the study

protocol.

Comparison

People exposed to long-term sickness absence

(lTSA) due to musculoskeletal disorders (MSD)

vs. people in the standard population

Same as above

lTSA due to MSD in severity category 1

vs. the

standard population

lTSA due to MSD in severity category 2–3 vs.

lTSA due to MSD in severity category 1

Exposed vs. not exposed to self-rated

musculoskeletal pain in the neck, shoulders, elbow,

forearm, hand or lower back

Follow-up period

1 February 2010–31

December 2015

Same as above

26 April 2010–31

December 2015

Same as above

1 January 2011–31

December 2015

Clinical end point

redeemed prescription for antidepressant drugs (ATC-code

n06A) or psychiatric hospital treatment with a depressive

mood disorder (ICD-10: F32–F33) as principal diagnosis

redeemed prescription for antidepressant drugs (ATC-code

n06A)

Psychiatric hospital treatment with a depressive mood

disorder (ICD-10: F32–F33) as principal diagnosis

redeemed prescription for antidepressant drugs (ATC-code

n06A) or psychiatric hospital treatment with a depressive

mood disorder (ICD-10: F32–F33) as principal diagnosis

Same as above

the first consultation with the sickness benefit office, the sick-listed person is classified into one of the following severity categories: (a)

likely to return to the labour force within three months, (b) unlikely to return to the labour force within three months but able to partici-

pate in activities aimed at facilitating a return or (c) unlikely to return to the labour force within three months and unable to participate in

activities.

back, and rr is the rate ratio for subsequent pre-

scribed antidepressants or psychiatric hospital treat-

ment for depression among employees with versus

without musculoskeletal pain in the concerned body

regions.

A 99% confidence interval for the PAF estimate

was obtained through Monte Carlo simulation.

Results

The first part of the project included 693,860 indi-

viduals (323,170 female). The mean (SD) age on 1

January 2010 was 43.1 (10.6) years among all

included individuals and 45.0 (9.9) years among the

individuals who were registered with MSD at a sick-

ness benefit office sometime between February 2010

and September 2012 (n=14,903). In total, we

observed 4111 incident cases of ‘psychiatric hospital

treatment for depression’ in 4,085,619 person-years

at risk; 52,835 incident cases of ‘redeemed prescrip-

tion for antidepressants’ in 3,923,451 person-years

at risk; and 53,262 incident cases of ‘prescribed anti-

depressants or psychiatric hospital treatment for

depression’ in 3,922,179 person-years at risk.

The second part of the project included 690,135

of the above-mentioned 693,860 individuals. A flow

chart of the inclusion/exclusion procedure is given in

Figure 1 of the Supplemental Appendix. Here, we

observed 50,257 incident cases of ‘prescribed antide-

pressants or psychiatric hospital treatment for depres-

sion’ in 3,920,246 person-years at risk.

The third part of the project included 9248 indi-

viduals (4797 female) of whom 4217 had self-rated

musculoskeletal pain according to the survey. The

mean (SD) age on 1 January 2011 was 46.6 (9.5)

years among participants with pain and 45.7 (9.8)

years among participants without pain. In total, we

observed 487 incident cases of ‘prescribed antide-

pressants or psychiatric hospital treatment for depres-

sion’ in 44,629 person-years at risk. A flow diagram

over the inclusion/exclusion procedure is given in

Figure 2 of the Supplemental Appendix.

The SES distributions of the included individuals

in the first and third parts of the project, respectively,

are given in Table II.

We found that long-term sickness absence due to

MSD statistically significantly predicted both psychi-

atric hospital treatment for depression with a rate

ratio of 2.55 (95% CI 2.12–3.07;

p<0.0001)

and

redeemed prescriptions for antidepressants with a

rate ratio of 3.06 (95% CI 2.91–3.23;

p<0.0001;

Table III). There was a dose–response relationship

with more severe episodes of MSD-related sickness

absence associated with a higher risk than less severe

episodes of MSD-related sickness absence

(p<0.0001; Table IV).

We furthermore found that self-rated musculo-

skeletal pain was a statistically significant predictor of

redeemed prescriptions for antidepressants or psy-

chiatric hospital treatment due to depression among

workers in the general population of Denmark

(p<0.0001; Table V). The PAF was estimated at 0.35

(99% CI 0.24–0.45).

Discussion

The results of the present study indicate that muscu-

loskeletal pain is an important predictor of indicators

Hannerz et al.

First part

6.6

3.6

18.5

22.7

31.0

6.6

2.4

8.6

100.0

Third part

499

439

1857

2159

2965

583

174

572

9248

5.4

4.7

20.1

23.3

32.1

6.3

1.9

6.2

100.0

Table II. Socio-economic status distribution of the participants in the first and third parts of the project, respectively.

Socio-economic status

Self-employed or assisting spouses

legislators, senior officials or managers

Professionals

Technicians or associate professionals

Workers in occupations that require skills at a basic level

Workers in elementary occupations

Unemployed

Gainfully occupied people with an unknown occupation

Total

45,520

25,287

128,128

157,789

215,155

45,472

16,565

59,944

693,860

Table III. Standardised rate ratios for prescribed antidepressants or psychiatric hospital treatment for depression among people on lTSA

due to MSD.

End point data

PCrr

nPr

PCrr or nPr

lTSA due to MSD

Yes

Person-years at risk

71,654

4,013,965

61,331

3,862,120

61,285

3,860,894

Cases

207

3904

2585

50,250

2601

50,661

rate ratio

2.55

1.00

3.06

1.00

3.06

1.00

99% CI

2.12–3.07

–

2.91–3.23

–

2.90–3.22

–

The

psychiatric central research register.

national prescription register.

Table IV. Standardised rate ratios for prescribed antidepressants or psychiatric hospital treatment for depression among people on lTSA

due to MSD stratified by severity category.

lTSA due to MSD

Yes, severity category 2–3

Yes, severity category 1

Standard population

rate

Person-years at risk

22,257

38,953

3,859,036

Cases

1346

1248

47,663

rate ratio

4.27

2.39

1.00

99% CI

3.98–4.59

2.22–2.58

–

ratio for severity category 2–3 vs. severity category 1=1.79 (99% CI 1.61–1.98).

Table V. Standardised rate ratios for prescribed antidepressants or psychiatric hospital treatment for depression among employees with

versus without musculoskeletal pain in the neck, shoulders, elbow, forearm, hand or lower back.

Musculoskeletal pain

Yes

Persons

4217

5031

Person-years at risk

20,097

24,532

Cases

320

167

rate ratio

2.17

1.00

99% CI

1.69–2.78

–

of depression (redeemed prescriptions for antide-

pressants and psychiatric hospital treatment for

depressive mood disorders). This finding was con-

sistent in both samples, and applied to both objec-

tively assessed and clinically diagnosed MSD among

sick-listed individuals and self-rated symptoms of

pain measured by a survey in the general working

population of Denmark.

Three previous studies have examined the pro-

spective relationship between musculoskeletal pain

and subsequent depression or depressive symptoms

among people in company-based or general working

age populations that are free from depressive symp-

toms at baseline [8,9,19]. The prospective relation-

ship has, moreover, been properly examined by

Gerrits et al. [10] in a study population predomi-

nately recruited from primary care and secondary

mental health care, as well as by Veronese et al. [20]

in a patient population consisting of predominately

older people who either suffered from or were at

increased risk of incurring osteoarthritis (OA) of the

knee. Gerrits et al. reported hazard ratios for depres-

sive symptoms of 2.64 (95% CI 1.42–4.91), 2.63

(95% CI 1.47–4.68) and 2.68 (95% CI 1.45–4.95)

Musculoskeletal complaints and depression

among participants with pain versus no pain in the

neck, back and joints, respectively. Veronese et al.

reported an odds ratio for depressive symptoms of

1.48 (95% CI 1.07–2.05) among people with multi-

site OA versus no OA

leino and Magni [19] investigated clinically assessed

MSD and self-rated musculoskeletal symptoms (ache,

stiffness, sensitivity to movement, numbness or pain) in

the neck/shoulders, lower back, upper limbs and lower

limbs as predictors for a subsequent change in depres-

sive symptom scores among 607 metal industry employ-

ees in Finland. The association between self-rated

musculoskeletal symptoms and change in depressive

symptoms was tested for each of the four body regions

as well as for all body regions combined. The same was

done for the association between clinical musculoskele-

tal findings and change in depressive symptoms. Hence,

a total of 20 tests of the prospective association between

musculoskeletal morbidity and depressive symptoms

were performed, of which none was statistically signifi-

cant.This null finding by leino and Magni [19] is not in

line with the findings of the present study – a discrep-

ancy which could be related to a lack of statistical power

in the study by leino and Magni.

Magni et al. [8] estimated the odds of having

depressive symptoms at an eight-year follow-up as a

function of chronic musculoskeletal pain at baseline

as 2.85 (95% CI 2.52–3.18) in a sample of 1790 peo-

ple aged 25–74 years from ‘the non-institutionalized

US population’. Depressive symptoms were defined

as a score of

⩾16

on the Center for Epidemiologic

Studies Depression (CES-D) scale [21]. The same

definition of depressive symptoms was used by Carrol

et al. [9] who estimated the hazard ratio for develop-

ment of depressive symptoms as a function of pain in

the neck or lower back in a sample of 845 residents of

Saskatchewan aged 20–69 years. The hazard ratios

were estimated as 2.10 (95% CI 1.09–4.04) for ‘mild

pain’, 1.98 (95% CI 0.91–4.32) for ‘intense, non-

disabling neck or low back pain’ and 2.45 (95% CI

1.06–5.69) for ‘disabling pain in the past six months’.

The findings by Magni et al. [8], Carrol et al. [9],

Gerrits et al. [10] and Veronese et al. [20] are in line

with the findings of the present study, suggesting that

MSD is an important predictor of depression. The

outcome data in these previous studies were, how-

ever, collected by volunteer participation in follow-

up interviews, which is open to bias from missing

follow-up data. Moreover, none of the previous stud-

ies were based on a representative sample of a general

working population. The present study does not

share these drawbacks and thereby adds certainty

about the strength of the prospective association

between musculoskeletal pain and depression in a

general working population.

Concerning the associations between working

conditions and depression, much attention has been

given over recent years to the potential link between

psychosocial working conditions and depression. A

multitude of studies show longitudinal associations

between psychosocial working conditions such as

high demands and low control, and the development

of depression [22,23], although methodological con-

cerns remain which preclude firm conclusions

regarding the causality of the association [23]. little

attention has been paid, however, to the role of physi-

cal working conditions and pain in these associations

[22]. The strong and consistent associations between

pain and depression in the present study suggest that

pain and physical working conditions are important

factors to consider as potential confounders or medi-

ators in future studies of associations between work-

ing conditions and depression. Our finding of a 35%

population attributable fraction of depression from

musculoskeletal pain among economically active

people furthermore suggests a potential to prevent

depression by strategies which targets work environ-

mental causes and consequences of MSD. Further

research is needed to explore this potential.

Strengths and limitations

The strengths of this study include the pre-published

study protocol [11] which specified all hypotheses,

inclusion criteria, data material and statistical meth-

ods of the study before exposure and outcome data

were linked. The protocol was followed, which means

that the study is free from hindsight bias and selective

outcome reporting. The use of national registers

eliminated bias from missing follow-up data, and the

problem of reversed causation was mitigated through

the exclusion of prevalent cases.

The study was further strengthened by the com-

plementary nature of our two data sets. The first data

set was used in sub-projects 1–2 to estimate the asso-

ciation between long-term sickness absence due to

MSD and subsequent depression. The data set was

large enough to verify that the association was pre-

sent not only when depression was operationalised

by antidepressant treatment, but also when it was

operationalised on the basis of psychiatric hospital

diagnoses. Consequently, the association found is not

likely to be attributable to antidepressants being pre-

scribed to alleviate pain [24]. It was, moreover, large

enough and had the necessary information to test for

a dose–response relationship between severity of

long-term sickness absence due to MSD and subse-

quent depression, allowing us to conclude that the

strength of the association increases with the severity

of MSD. The drawback of the first data set was that it

Hannerz et al.

Fifth, some individuals in the comparison group

may have experienced pain prior to baseline, and

some of them would have experienced pain during

the follow-up, which would dilute the exposure con-

trast and thereby bias the estimation of rate ratios for

exposed versus non-exposed people towards unity.

Moreover, in a study on the relationship between

retirement and antidepressant use, Oksanen et al.

defined antidepressant use as the purchase of antide-

pressants of at least 30 defined daily dosages (DDD)

[29]. In the present project, we did not have access to

information about the DDD of the prescriptions.

One redeemed prescription was enough for the case

definition to be fulfilled. The average severity of the

cases of the present study is therefore expected to be

less than it would have been if we had required the

purchase of a pre-specified amount of daily dosages

before the case definition was fulfilled. We cannot

rule out the possibility that the estimated rate ratios

for antidepressant use would have been lower if our

case definition had been based on a certain amount

of daily dosages instead of a redeemed prescription

without further specifications.

Conclusions

To conclude, we found strong and consistent longi-

tudinal associations between MSD and indicators of

depression (redeemed prescriptions for antidepres-

sants and psychiatric hospital treatment for depres-

sive mood disorders) in two separate cohorts from

the Danish workforce. These findings suggest that

musculoskeletal pain is an important predictor of

depression, which should be considered in future

studies on the aetiology of depression.

Acknowledgements

The data of the project were provided the national

research Centre for the Working Environment and

Statistics Denmark. The authors would like to

acknowledge all researchers and participants who

contributed to the data collection in the Danish

national return-to-work (rTW) programme and the

Danish Work Environment cohort study, thus ena-

bling the present study.

Declaration of conflicting interests

The authors declare that there is no conflict of

interest.

Funding

The authors received no financial support for the

research, authorship and/or publication of this

article.

did not allow differentiation between effects from

MSD and other effects of being on long-term sick

leave. long-term sickness absence may, for example,

be associated with job insecurity, and employees on

long-term sickness absence risk unemployment [25],

which are both predictors of depressive symptoms

[26]. A positive association between long-term sick-

ness absence due to MSD and depression in Denmark

would therefore not necessarily mean that there is a

positive association between musculoskeletal pain

and depression in the general workforce of Denmark.

Our second data set rectified this shortcoming by

allowing us to estimate the association between mus-

culoskeletal pain and subsequent use of antidepres-

sants or hospital treatment due to depression in a

random sample of the Danish labour force.

However, some limitations of the study should be

noted. First, antidepressants are not only used to

treat depression. They are also prescribed for many

other conditions, such as pain, anxiety and insomnia

[24]. It is, moreover, known that depression can be

treated with medication other than antidepressants,

for example lithium [27]. A rate ratio of redeemed

prescriptions for antidepressants is therefore quite a

rough estimate of the association between pain and

medically treated depression, and this should be

taken into account in the interpretation of the results.

Second, we cannot rule out the possibility of

detection bias. All else equal, depressed people with

musculoskeletal pain would have more reasons to

visit a medical doctor than depressed people without

musculoskeletal pain. MSD may thereby be associ-

ated with an increased probability that depression

will be detected and treated, which would bias rate

ratios upwards.

Third, the pain scores and the diagnostic criteria

for depression [28] are based on self-reported symp-

toms of physical and mental discomfort, respectively.

People who are prone to tone down/exaggerate their

physical discomforts may also be prone to tone down/

exaggerate their mental discomforts, which would

bias rate ratios upwards.

Fourth, in our third sub-project, we used the prev-

alence of pain among the responders of our national

survey to estimate the PAF of depression due to mus-

culoskeletal pain among all economically active peo-

ple in Denmark. The survey sample was selected at

random from the target population, but the response

rate was low (48%). We therefore cannot rule out the

possibility that the PAF estimation was biased by

non-participation. If the prevalence was greater

among the non-responders than it was among the

responders, then the PAF estimate would be biased

downwards. If the opposite was true, then it would be

biased upwards.

Musculoskeletal complaints and depression

ORCID iD

Harald Hannerz

-0499

https://orcid.org/0000-0003-0687

Supplemental material

Supplemental material for this article is available

online.

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