Interventions to improve return to work in depressed people

Karen Nieuwenhuijsen; Jos H Verbeek; Angela Neumeyer-Gromen; Arco C Verhoeven; Ute Bültmann; Babs Faber

doi:10.1002/14651858.CD006237.pub4

Interventions to improve return to work in depressed people

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Versión publicada: 14 octubre 2020 Historial de versiones

https://doi.org/10.1002/14651858.CD006237.pub4

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Abstract

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Background

Work disability such as sickness absence is common in people with depression.

Objectives

To evaluate the effectiveness of interventions aimed at reducing work disability in employees with depressive disorders.

Search methods

We searched CENTRAL (The Cochrane Library), MEDLINE, Embase, CINAHL, and PsycINFO until April 4th 2020.

Selection criteria

We included randomised controlled trials (RCTs) and cluster‐RCTs of work‐directed and clinical interventions for depressed people that included sickness absence days or being off work as an outcome. We also analysed the effects on depression and work functioning.

Data collection and analysis

Two review authors independently extracted the data and rated the certainty of the evidence using GRADE. We used standardised mean differences (SMDs) or risk ratios (RR) with 95% confidence intervals (CI) to pool study results in studies we judged to be sufficiently similar.

Main results

In this update, we added 23 new studies. In total, we included 45 studies with 88 study arms, involving 12,109 participants with either a major depressive disorder or a high level of depressive symptoms.

Risk of bias

The most common types of bias risk were detection bias (27 studies) and attrition bias (22 studies), both for the outcome of sickness absence.

Work‐directed interventions

Work‐directed interventionscombined with clinical interventions

A combination of a work‐directed intervention and a clinical intervention probably reduces sickness absence days within the first year of follow‐up (SMD ‐0.25, 95% CI ‐0.38 to ‐0.12; 9 studies; moderate‐certainty evidence). This translates back to 0.5 fewer (95% CI ‐0.7 to ‐0.2) sick leave days in the past two weeks or 25 fewer days during one year (95% CI ‐37.5 to ‐11.8). The intervention does not lead to fewer persons being off work beyond one year follow‐up (RR 1.08, 95% CI 0.64 to 1.83; 2 studies, high‐certainty evidence). The intervention may reduce depressive symptoms (SMD ‐0.25, 95% CI ‐0.49 to ‐0.01; 8 studies, low‐certainty evidence) and probably has a small effect on work functioning (SMD ‐0.19, 95% CI ‐0.42 to 0.06; 5 studies, moderate‐certainty evidence) within the first year of follow‐up.

Stand alone work‐directed interventions

A specific work‐directed intervention alone may increase the number of sickness absence days compared with work‐directed care as usual (SMD 0.39, 95% CI 0.04 to 0.74; 2 studies, low‐certainty evidence) but probably does not lead to more people being off work within the first year of follow‐up (RR 0.93, 95% CI 0.77 to 1.11; 1 study, moderate‐certainty evidence) or beyond (RR 1.00, 95% CI 0.82 to 1.22; 2 studies, moderate‐certainty evidence). There is probably no effect on depressive symptoms (SMD ‐0.10, 95% ‐0.30 CI to 0.10; 4 studies, moderate‐certainty evidence) within the first year of follow‐up and there may be no effect on depressive symptoms beyond that time (SMD 0.18, 95% CI ‐0.13 to 0.49; 1 study, low‐certainty evidence). The intervention may also not lead to better work functioning (SMD ‐0.32, 95% CI ‐0.90 to 0.26; 1 study, low‐certainty evidence) within the first year of follow‐up.

Psychological interventions

A psychological intervention, either face‐to‐face, or an E‐mental health intervention, with or without professional guidance, may reduce the number of sickness absence days, compared with care as usual (SMD ‐0.15, 95% CI ‐0.28 to ‐0.03; 9 studies, low‐certainty evidence). It may also reduce depressive symptoms (SMD ‐0.30, 95% CI ‐0.45 to ‐0.15, 8 studies, low‐certainty evidence). We are uncertain whether these psychological interventions improve work ability (SMD ‐0.15 95% CI ‐0.46 to 0.57; 1 study; very low‐certainty evidence).

Psychological interventioncombined with antidepressant medication

Two studies compared the effect of a psychological intervention combined with antidepressants to antidepressants alone. One study combined psychodynamic therapy with tricyclic antidepressant (TCA) medication and another combined telephone‐administered cognitive behavioural therapy (CBT) with a selective serotonin reuptake inhibitor (SSRI). We are uncertain if this intervention reduces the number of sickness absence days (SMD ‐0.38, 95% CI ‐0.99 to 0.24; 2 studies, very low‐certainty evidence) but found that there may be no effect on depressive symptoms (SMD ‐0.19, 95% CI ‐0.50 to 0.12; 2 studies, low‐certainty evidence).

Antidepressant medication only

Three studies compared the effectiveness of SSRI to selective norepinephrine reuptake inhibitor (SNRI) medication on reducing sickness absence and yielded highly inconsistent results.

Improved care

Overall, interventions to improve care did not lead to fewer sickness absence days, compared to care as usual (SMD ‐0.05, 95% CI ‐0.16 to 0.06; 7 studies, moderate‐certainty evidence). However, in studies with a low risk of bias, the intervention probably leads to fewer sickness absence days in the first year of follow‐up (SMD ‐0.20, 95% CI ‐0.35 to ‐0.05; 2 studies; moderate‐certainty evidence). Improved care probably leads to fewer depressive symptoms (SMD ‐0.21, 95% CI ‐0.35 to ‐0.07; 7 studies, moderate‐certainty evidence) but may possibly lead to a decrease in work‐functioning (SMD 0.5, 95% CI 0.34 to 0.66; 1 study; moderate‐certainty evidence).

Exercise

Supervised strength exercise may reduce sickness absence, compared to relaxation (SMD ‐1.11; 95% CI ‐1.68 to ‐0.54; one study, low‐certainty evidence). However, aerobic exercise probably is not more effective than relaxation or stretching (SMD ‐0.06; 95% CI ‐0.36 to 0.24; 2 studies, moderate‐certainty evidence). Both studies found no differences between the two conditions in depressive symptoms.

Authors' conclusions

A combination of a work‐directed intervention and a clinical intervention probably reduces the number of sickness absence days, but at the end of one year or longer follow‐up, this does not lead to more people in the intervention group being at work. The intervention may also reduce depressive symptoms and probably increases work functioning more than care as usual. Specific work‐directed interventions may not be more effective than usual work‐directed care alone. Psychological interventions may reduce the number of sickness absence days, compared with care as usual. Interventions to improve clinical care probably lead to lower sickness absence and lower levels of depression, compared with care as usual. There was no evidence of a difference in effect on sickness absence of one antidepressant medication compared to another. Further research is needed to assess which combination of work‐directed and clinical interventions works best.

PICO

Population

Intervention

Comparison

Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Plain language summary

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What are the best ways to help people with depression go back to work?

What is depression?

Depression is a common mental health problem that can cause a persistent feeling of sadness and loss of interest in people, activities, and things that were once enjoyable. A person with depression may feel tearful, irritable, or tired most of the time, and may have problems with sleep, concentration, and memory.

Depression may affect people's ability to work. People with depression may be absent from work (off sick), or feel less able to cope with working.

Going back to work

Reducing depressive symptoms may help people with depression to go back to work. Treatments include medications and psychological (talking) therapies, or a combination of both. Changes at the workplace could also help, such as:

changing a person's tasks or working hours;

supporting them in a gradual return to work; or

helping them to cope better with certain work situations.

Why we did this Cochrane Review

Work can improve a person's physical and mental well‑being; it helps build confidence and self‐esteem, allows people to socialise, and provides money. We wanted to find out if workplace changes and clinical programmes could help people with depression to return to work.

What did we do?

We searched for studies that looked at whether workplace changes and clinical programmes affected the amount of sick leave taken by people with depression. Clinical programmes included: medicines (anti‐depressants); psychological therapies; improved healthcare by doctors; and other programmes such as exercise and diet.

Search date: we included evidence published up to 4 April 2020.

What we found

We found 45 studies in 12,109 people with depression. The studies took place in Europe (34 studies), the USA (8), Australia (2) and Canada (1).

The effects of 'care as usual' were compared with those of workplace changes and clinical programmes to find out:

how many days people with depression were on sick leave

how many people with depression were off work;

people's symptoms of depression; and

how well people with depression could cope with their work.

What are the results of our review?

Our main findings within the first year of follow‐up, for workplace changes or treatments compared with usual care, are listed below.

Workplace changes combined with a clinical programme:

probably reduce the number of days on sick leave (on average, by 25 days for each person over one year; 9 studies; 1292 participants);

do not reduce the number of people off work (2 studies; 1025 participants);

may reduce symptoms of depression (8 studies; 1091 participants); and

may improve ability to cope with work (5 studies; 926 participants).

Workplace changes alone:

may increase the number of days on sick leave (2 studies, 130 participants);

probably do not lead to more people off work (1 study; 226 participants);

probably do not affect symptoms of depression (4 studies; 390 participants); and

may not improve ability to cope with work (1 study; 48 participants).

Improved healthcare alone:

probably reduces the number of days on sick leave, by 20 days (in two, well‐conducted studies in 692 participants, although not in all 7 studies, in 1912 participants);

probably reduces symptoms of depression (7 studies; 1808 participants); and

may reduce ability to cope with work (1 study; 604 participants).

Psychological therapies alone:

may reduce the number of days off work, by 15 days (9 studies; 1649 participants); and

may reduce symptoms of depression (8 studies; 1255 participants).

We are uncertain if psychological therapies alone affect people's ability to cope with work (1 study; 58 participants).

How reliable are these results?

Our confidence in these results is mostly moderate to low. Some findings are based on small numbers of studies, in small numbers of participants. We also found limitations in the ways some studies were designed, conducted and reported.

Key messages

Combining workplace changes with a clinical programme probably helps people with depression to return to work more quickly and to take fewer days off sick. We need more evidence to assess which combination of workplace changes and clinical programmes works best.

Improved healthcare probably also helps people with depression to take fewer days off sick.

Authors' conclusions

Implications for practice

A combination of a work‐directed and a clinical intervention probably reduces the number of sickness absence days but not the number of people at work at the end of follow up. Specific work‐directed intervention may not be more effective than usual work‐directed care alone. We further found that psychological interventions may reduce the number of sickness absence days compared to care as usual. These interventions were either provided face‐to‐face, or online, with or without guidance from a care provider. Improving the management of clinical care probably also leads to fewer days of sickness absence and, probably reduces the depressive symptoms. The effects of one antidepressant medication compared with another were inconsistent without a clear pattern.

Implications for research

More research is needed on combined work‐directed interventions combined with clinical interventions. Such interventions probably reduce sickness absence to a small degree but it is unclear which type and combination of work‐directed and clinical intervention is the most effective and what is the mechanism by which this intervention apparently works. For example, it is unclear if it is most important to add work‐directed intervention to clinical treatment such as adding overcoming barriers for return‐to‐work to existing treatment such as CBT or the other way around to add clinical intervention to existing return‐to‐work services.

Most studies currently compare the intervention to care as usual. This makes comparison across studies difficult as the content of care as usual is often not specified. In future studies care as usual should be specified and it should be reported how this differs from the intervention.

Future studies should also elucidate the apparent discrepancy between the reduction in sickness absence and the lack of effect on the proportion of persons at work at end of follow‐up.

Studies should focus solely on patients with depression because it is unclear if mechanisms of action differ between patient groups with various mental health problems. In addition, it has been shown that well‐powered studies with depressed persons are possible. More of these studies are needed. This will also prevent the decrease in validity of the studies when analysing only subgroups of patients with depression.

To facilitate the synthesis of evidence from various intervention studies, the occupational health field should work towards standardising and validating measures of sickness absence that preferably should be measured in an objective way for example based on registry data.

For future reviews including sickness absence as an outcome measure, it is advisable to report standardised mean differences instead of means as this takes into account the differences in measurement methods.

Summary of findings

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Summary of findings 1. Work‐directed plus clinical intervention compared to care as usual in depressed people, medium‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Work‐directed plus clinical intervention compared to care as usual (medium‐term) in depressed people
Patients: Depressed persons Setting: Various: workplaces, outpatient and occupational healthcare Intervention: Work‐directed plus clinical Control: Care as usual (medium‐term)
Outcomes	Risk with care as usual	Risk with work‐directed intervention plus clinical intervention	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sickness absence days	‐	SMD 0.25 SD lower (0.38 lower to 0.12 lower)	‐	1292 (9 RCTs)	⊕⊕⊕⊝ MODERATE ¹	The SMD translates back to ‐0.5 days per 2 weeks (CI ‐0.7 to ‐0.2) or ‐24.7 days in 12 months (‐37.5 to ‐11.8).
On sick leave	417 per 1.000	451 per 1.000 (267 to 764)	RR 1.08 (0.64 to 1.83)	1025 (2 RCTs)	⊕⊕⊕⊕ HIGH
Depressive symptoms‐	‐	SMD 0.25 SD lower (0.49 lower to 0.01 lower)	‐	1091 (8 RCTs)	⊕⊕⊝⊝ LOW ^{2 3}
Work functioning	‐	SMD 0.19 SD lower (0.43 lower to 0.06 higher)	‐	926 (5 RCTs)	⊕⊕⊝⊝ LOW ^{1 4 5}
The risk in the intervention group (and the 95% CI) is based on the risk in the control group and the relative effect of the intervention (and the 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; RR: Risk ratio; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹A majority of the studies in the meta‐analysis (in terms of weights) showed high or unclear risk on the randomisation items (sequence and concealment), blinded outcome assessment or attrition. We therefore rated down one level due to a high risk of bias. ²Depression is self‐reported and participants were not blinded. We rated down one level due to a high risk of bias. ³Study effects varied with some clearly indicating beneficial results and some not. We rated down one level due to imprecision. ⁴Rated down one level due to inconsistency (I² 61%). ⁵Pooled effect size includes small harmful effec. Rated down one level due to wide CI (imprecision)

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Summary of findings 2. Work‐directed intervention compared to care as usual in depressed people, medium‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Work‐directed intervention compared to care as usual in depressed people
Patient or population: Depressed persons Setting: Workplace and occupational healthcare Intervention: Work‐directed Comparison: Care as usual (medium‐term)
Outcomes	Risk with care as usual	Risk with work‐directed intervention	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sickness absence days, medium‐term follow‐up	‐	SMD 0.39 higher (0.04 higher to 0.74 higher)	‐	130 (2 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}	The SMD translates back to + 0.7 days in two weeks (95% CI 0.1 to 1.3) or + 38 days in 12 months (95% CI 3.9 to 73).
Off work, medium‐term follow‐up	708 per 1.000	658 per 1.000 (545 to 786)	RR 0.93 (0.77 to 1.11)	226 (1 RCT)	⊕⊕⊕⊝ MODERATE ³
Depressive symptoms, medium‐term follow‐up	‐	SMD 0.1 lower (0.3 lower to 0.1 higher)	‐	390 (4 RCTs)	⊕⊕⊕⊝ MODERATE ⁴
Work functioning, medium‐term follow‐up	‐	SMD 0.32 lower (0.9 lower to 0.26 higher)	‐	48 (1 RCT)	⊕⊕⊝⊝ LOW ^{3 5}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; RR: Risk ratio; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹One study with unclear risk and one with serious risk of bias. Rated down one level due to high risk of bias. ²Two studies with 130 participants. CI includes harms and benefits. Rated down one level due to imprecision. ³Based on one study with small number of participants, rated down one level due to to imprecision. ⁴Includes studies with high risk of bias. Rated down one level due to high risk of bias. ⁵One study with unclear risk of bias. Rated down with one level due to high risk of bias.

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Summary of findings 3. Psychological intervention compared to care as usual in depressed people, medium‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Psychological intervention compared to care as usual in depressed people
Patient or population: Depressed persons Setting: Various: workplaces, primary care, insurance institute and academic hospital Intervention: Psychological intervention Comparison: Care as usual
Outcomes	Risk with psychological intervention	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sickness absence days, medium‐term follow‐up	SMD 0.15 lower (0.28 lower to 0.03 lower)	1649 (9 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}	The SMD translates back to ‐0.3 days per 2 weeks (95% CI ‐0.5 to ‐0.1) or ‐14.7 days in 12 months (95% CI ‐27.6 to ‐3.0).
Depressive symptoms, medium‐term follow‐up	SMD 0.3 lower (0.45 lower to 0.15 lower)	1255 (8 RCTs)	⊕⊕⊝⊝ LOW ^{2 3}
Work ability, medium‐term follow‐up	SMD 0.05 higher (0.46 lower to 0.57 higher)	58 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{4 5}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹In most studies, the outcome was self‐reported, leading to risk of bias in outcome assessment. There was also large attrition. Rated down one level due to high risk of bias. ²Funnel plot shows missing small studies with no effect or harmful effect. Rated down one level due to risk of publication bias. ³Outcomes self‐reported in unblinded studies. Rated down one level due to high risk of bias ⁴CI includes appreciable harms and benefits. Sole study. Rated down two levels due to imprecision. ⁵One study with unclear risk of bias. Rated down one level due to high risk of bias.

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Summary of findings 4. Improved care compared to care as usual in depressed people, medium‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Improved care compared to care as usual in depressed persons
Patient or population: Depressed persons Setting: Primary Care and community mental health Intervention: Improved Care Comparison: Care as usual
Outcomes	Risk with care as usual	Risk with improved care	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sickness absence days, medium‐term follow‐up	‐	SMD 0.06 lower (0.15 lower to 0.04 higher)¹	‐	1912 (7 RCTs)	⊕⊕⊕⊝ MODERATE ²	The SMD translates back to ‐0.1 days per 2 weeks (95% CI ‐0.3 to 0.1) or ‐5.9 days in 12 months (95% CI ‐14.8 to 3.9). The SMD of the sensitivity analysis¹ translates back to ‐0.4 days per 2 weeks (95% CI ‐0.6 to ‐0.1) or ‐19.7 days in 12 months (95% CI ‐34.5 to ‐4.9).
Off work, medium‐term follow up	496 per 1.000	516 per 1.000 (402 to 655)	RR 0.97 (0.77 to 1.22)	362 (1 RCT)	⊕⊕⊝⊝ LOW ^3,4
Depressive symptoms, medium‐term follow‐up	‐	SMD 0.21 SD lower (0.35 lower to 0.07 lower)	‐	1808 (7 RCTs)	⊕⊕⊕⊝ MODERATE ²
Work functioning, medium‐term follow‐up	‐	SMD 0.5 higher (0.34 higher to 0.66 higher)	‐	604 (1 RCT)	⊕⊕⊕⊝ MODERATE ⁵
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; RR: Risk ratio; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
1 A sensitivity analysis revealed that two RCTs with a lower risk of bias found a SMD of 0.20 lower (0.35 lower to 0.05 lower); moderate‐certainty evidence). 2 Majority of studies at high risk; downgraded with one level due to high risk of bias. 3 One study at high risk of bias, downgraded with one level due to high risk of bias. 4 One study with less than 400 participants, downgraded with one level due to imprecision 5 Study with unblinded outcome assessment, rated down one level due to high risk of bias.

Background

Description of the condition

Depression is a major public health problem, with 298 million cases of major depressive disorders at any time point in 2010 (Ferrari 2013). The worldwide point prevalence of depressive disorder was 4.4% in both 2005 and 2010 (Ferrari 2013). Symptoms of depressive disorder include the presence of one or two core symptoms of low mood and loss of interest, coupled with other symptoms such as feelings of inadequacy and hopelessness, sleep disturbance, weight change, fatigue, impaired concentration, agitation or slowing down of movement and thought, and suicidal ideation (APA 2013). Depressive disorders can be classified along a continuum by the levels of symptom severity, number of mental or physical symptoms, and duration. Corresponding diagnostic categories range from persistent depression (dysthymia) and subclinical states (minor depressive disorder) to major depressive disorder (APA 1994; APA 2013).

Besides the serious consequences in terms of individual suffering, depression has a large impact on social functioning and the ability of patients to work (Evans‐Lacko 2016; Hirschfeld 2000; Lerner 2008). In a population of US workers, the 12‐month prevalence of major depressive disorder was found to be 6% and was associated with 27.2 lost workdays per ill worker per year (Kessler 2006). The economic burden of depressed individuals in the US was US dollars (USD) 210.5 billion in 2010, of which 50% were attributable to workplace costs (Greenberg 2015). The high prevalence of depressive disorders, combined with the impact on work disability, has extensive societal consequences. In 1990, major depressive disorders were the 15th leading contributor to the global burden of disease in terms of Disability Adjusted Life Years (DALYs), which is the sum of years of productive life lost due to premature mortality and the years of productive life lost due to disability. Data from the Global Burden of Disease study showed that depressive disorders were ranked the 11th leading contributor (Murray 2012).

While working is important from a societal point of view, work is also an important aspect of the quality of life of individuals (Bowling 1995). Work provides income, structure, and social interactions. One salient consequence of depression is absenteeism, but depression can also affect the at‐work productivity for workers (Lerner 2008). Depressed workers experience specific limitations in their ability to function at work. These limitations include performing mental and interpersonal tasks (Adler 2006; Burton 2004). The quality of work performance can also be affected, as was shown in studies focusing on errors and safety issues (Haslam 2005; Suzuki 2004). Depressed workers may need to make an extra effort to be productive during their work (Dewa 2000), which may lead to spill‐over effects of fatigue after work.

Description of the intervention

Work disability of depressed workers can be targeted by interventions. First of all, work‐directed interventions aim to ameliorate the consequences of the depressive disorder on the ability to work. These types of interventions either target the work itself, by modifying the job task, or (temporarily) reduce the working hours. Work‐directed interventions can also support the worker in dealing with the consequences of their depression at the workplace.

Second, clinical interventions aimed at reducing depression symptoms may improve work ability (Hees 2013b). Current clinical practice guidelines for the treatment of major depressive disorder recommend pharmacotherapy, psychotherapy, or a combination of both (APA 2010; NICE 2010). Pharmacologic treatment for major depressive disorder includes antidepressant medication such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAO inhibitors), and selective norepinephrine reuptake inhibitors (SNRIs). With regard to psychotherapy, cognitive behavioural therapy (CBT) and interpersonal therapy in particular are considered effective treatment options (NICE 2010). Exercise has been increasingly used as an alternative to pharmacological or psychotherapeutic interventions (Cooney 2013).

How the intervention might work

Work‐directed interventions are deemed to reduce work disability by creating a work environment better suited for a depressed worker, such as modifying work tasks or working hours. Moreover, the worker can be supported in dealing with the depression at work by a gradual return to work program or by enhancing skills to cope with work situations (Lagerveld 2012). Clinical interventions may reduce work disability by reducing depressive symptoms, thereby eliminating the obstacles to working.

Why it is important to do this review

Considering the impact of depressive disorders on the occupational health of many affected workers, it is vital to know what types of interventions are effective in improving occupational health. In the first version of this review, in 2008, we concluded that there was an urgent need to evaluate interventions that address work issues in future research. Since then, several such studies have been published underpinning the need for an update of the review.

Objectives

The goal of this review was to evaluate the effectiveness of interventions aimed at reducing sickness absence in employees with depressive disorders.

We considered the effectiveness of two types of interventions:

work‐directed interventions, i.e. addressing the work or the work‐worker interface as part of the clinical treatment or as a stand‐alone intervention; and
clinical interventions, i.e. treatment of depressive disorder without a focus on work.

Methods

Criteria for considering studies for this review

Types of studies

We included all randomised controlled trials (RCTs), including cluster‐RCTs, in this review. We did not use any language restrictions.

Types of participants

Patient characteristics and setting

The population was limited to adult (i.e. more than 17 years old) workers (employees or self‐employed). We included participants from occupational health settings, primary care, or outpatient care settings. We based the selection of the studies on the primary outcome only. We still included studies if less than 50% of the participants were not employed.

Diagnosis

We defined depressive disorder as a main diagnosis fulfilling the criteria of the Diagnostic and Statistical Manual (DSM‐IV) (APA 1994; APA 2013), the Research Diagnostic Criteria (RDC) (Spitzer 1979), or the International Classification of Disease (ICD‐10) (WHO 1992) for one of the following disorders: dysthymic disorder, minor depressive disorder, or major depressive disorder. We also included studies that defined depressive disorder as a level of depressive symptoms assessed by validated self‐report instruments published in peer‐reviewed journals. An example is the Beck Depression Inventory (BDI) (Beck 1987); or clinician‐rated instruments such as the Hamilton Depression Rating Scale (HDRS) (Hamilton 1967) or the Montgomery–Åsberg Depression Rating Scale (MADRS) (Montgomery 1979).

Exclusion criteria

We excluded studies involving workers with a primary diagnosis of a common mental disorder other than a depressive disorder. We did not exclude workers with a co‐morbidity from other common mental disorders (such as anxiety disorders), but we did exclude workers with bipolar disorders or depressive disorders with psychotic features.

Types of interventions

We included all interventions aimed at reducing work disability. Naming and classifying interventions that aim to improve return to work is difficult. Health‐care interventions aiming to enhance return to work are mainly based on two mechanisms. One is improving conditions related to work, such as helping workers with depressive symptoms to overcome barriers that prevent them from working such as reducing work hours, changing tasks, light duty, graded work exposure addressing causes of depression at work such as a conflict, or supporting the worker in coping with the consequences of their depression in the workplace. We called these types of interventions ‘work‐directed interventions’ and we did not use any subcategories of these interventions. The other mechanism is through improvement of depressive symptoms as is usual in treatment situations, assuming that the symptoms are the main barrier for not being at work. We called these interventions ‘clinical interventions.' For clinical interventions we made distinctions among the following treatment modalities: psychological or psychiatric treatment, antidepressants, a combination of these two, and other interventions such as improved care, exercise and diet.

We compared work‐directed interventions, clinical interventions, and a combination of both types against any other intervention, no intervention or care as usual.

Types of outcome measures

In this review, we operationalised reduction in work disability as a reduction in sickness absence and as enhancement in work functioning.

Primary outcomes

The main outcome measure in this review was sickness absence, either measured as sickness absence days during the follow‐up period or employment status after a period of time, categorised as being 'off work' or 'at work.' Sickness absence data could be extracted from the employee attendance records, the files of a compensation board, or it could be self‐reported.

Secondary outcomes

When available, we included the following secondary outcomes from the included studies.

Depression (either dichotomously or continuously measured).
Work functioning (Nieuwenhuijsen 2010). Examples of work functioning measures are the Endicott Work Productivity Scale (EWPS) (Endicott 1997), the Sheehan Disability Scale (SDS) (Sheehan 1996) and the Work Role Functioning Questionnaire (WRFQ) (Abma 2012). We only included instruments that separately measured work functioning (instead of work and other activities combined). The outcome 'work ability' (Ilmarinen 2005) was also considered as a work functioning outcome.

We did not include other outcomes such as employee satisfaction, general social functioning (not work‐specific), or quality of life scales.

We considered the effects measured with all the above instruments on the following time‐scales:

short‐term, up to two months;
medium‐term, over two months to one year; and
long‐term, over one year.

Search methods for identification of studies

Electronic searches

We conducted the original search strategy for the first version of this review in 2006, using no limits on publication date (Appendix 1). We updated the search for the 2014 update and used this search strategy again for the 2020 update (Appendix 2). For this update, we searched the following electronic databases: CENTRAL (The Cochrane Library), MEDLINE, PsycINFO, Embase, and CINAHL up to the 4 April 2020. We used three types of terms: depression‐related words combined with work‐related words and database‐specific methodological filter terms. We adapted the search terms for PsycINFO, Embase, and CINAHL from the MEDLINE search to fit the specific requirements of those databases. For CENTRAL, we replaced the methodological filter by a filter to identify trials.

We based the selected work‐related search terms on previous studies. Work* and occupation* are sensitive single terms used to locate occupational health studies, as advocated by Verbeek (Verbeek 2005). Furthermore, we selected database‐specific terms relevant to our objective from a study testing which work‐related search terms are best suited for literature searching on chronic disease (rheumatoid arthritis, diabetes mellitus, hearing problems, and depression) and work (Haafkens 2006).

Searching other resources

We checked the reference lists of all articles that we retrieved as full papers and of all retrieved systematic and narrative reviews in order to identify further potentially eligible studies.

Data collection and analysis

Selection of studies

Pairs of review authors decided if a study did not fulfil the criteria for selection, and we excluded the study at that point. We excluded studies in this phase only if the study did not include participants with depressive disorders or it was not a controlled intervention study. When it was not clear whether sickness absence was measured, we retrieved the full article before deciding upon exclusion. We then examined the full text publications of the remaining studies in order to decide which studies fulfilled all inclusion criteria. We documented the reasons for exclusion at that stage. The two review authors discussed any disagreement about the inclusion of studies until they reached consensus. If they could not resolve their difference of opinion, they consulted a third review author (JV). All articles published in languages other than English were translated or assessed for inclusion by a native speaker.

Data extraction and management

We constructed a data extraction form that enabled the review authors to extract the data from the included studies. For each study, one review author filled out the forms; this form was checked by a second review author (AN, AV, BF, CF, HH, KN, and UB participated in data extraction). Review authors solved differences of opinion by discussion. When only a proportion of the study population was workers, we extracted the data for that subgroup from the article. When these data were not reported, we asked the original study authors to provide the data for this subgroup. We used the same procedure for studies where only a proportion of the study population was depressed.

Assessment of risk of bias in included studies

Pairs of review authors independently assessed the risk of bias of the included studies. We used the following items to assess risk of bias in the included studies: random sequence generation (selection bias), allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), and selective reporting (reporting bias). We evaluated risk associated with incomplete outcome data or with blinding of outcome assessments separately for sickness absence, depressive symptoms and where applicable also for work functioning. As the latter outcome was not often used, we did not report the risk of bias for work functioning separately in the risk of bias tables. We assessed the risk of bias in RCTs and cluster‐RCTs by using Cochrane's 'Risk of bias' tool (Higgins 2011).

With regard to the risk of attrition bias, we calculated the percentage lost to follow up taking the number randomised as the starting point and the number analyzed at the latest follow‐up measurement as the endpoint. We assigned a high risk of attrition bias to studies with a percentage of participants lost to follow up of more than 20%, and a low risk for studies with less than 10% lost to follow. The risk of attrition bias for studies with 10% to 20% lost to follow up depended on whether the analyses of results accounted for attrition sufficiently.

We rated each potential source of bias as ‘high risk’ of bias, ‘low risk’ of bias, or ‘unclear risk’ of bias in the ‘Risk of bias’ table. Next, we constructed a ‘Risk of bias' summary figure together with an overview ‘Risk of bias' graph as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Where information on risk of bias related to unpublished data or correspondence with a researcher, we noted this in the 'Risk of bias' table.

Measures of treatment effect

We plotted the results of each trial as means and standard deviations (SD) for continuous outcomes. For each timescale (short‐term, medium‐term, and long‐term), we selected the last available observation within this period for the meta‐analysis. For the primary outcome measure, that is sickness absence days, we transformed the number of days or hours worked during the follow up into days of sickness absence. To do so, we extracted the hours or days worked from the mean number of hours a full‐time employee would work in that specific country. When transforming the data from days worked to days not worked, the SDs did not need to be transformed. When transforming the data from hours to days, we divided both the means and SDs by eight. Studies used different time spans during which they measured the number of sickness absence days. Therefore, for sickness absence days we used the standardized mean difference (SMD) with a 95% confidence interval (CI) between the intervention and control groups as the summary effect measure. In order to aid interpretability of these SMDs, we also present the translation of the SMD in terms of the two most commonly used outcome measures; sickness absence days over a two‐week period and over a one‐year period. To this end, we multiplied the SMD by the median of the SDs of the intervention groups using these outcomes.

For the secondary outcome measures, we also used SMDs because it is likely that these outcomes were measured with different instruments. We chose to treat ordinal variables using a scale of more than five categories as continuous variables (it should be noted that this choice was based on arbitrary criteria). We dichotomised scales with fewer than five categories. For dichotomous data, we calculated the risk ratios (RRs) and 95% CIs.

For depression data, where studies presented both dichotomous and continuous data, we preferred the continuous outcome measures since the majority of the studies presented these.

Unit of analysis issues

For studies that employed a cluster‐randomised design and did not consider the design effect in the analyses, we planned to calculate the design effect by following the methods presented in Donner 2002 based on a fairly large assumed intra‐cluster correlation of 0.10. However, the cluster‐RCTs included in the review reported negligible intra‐cluster correlations. Therefore, we did not adjust the measures of effect presented by the authors.

Dealing with missing data

If the SDs (continuous data) or numbers of outcomes for each group (dichotomous data) were not presented in the publication, we contacted the authors with a request to provide these data. Whenever authors were unable or unwilling to provide this information, we calculated SDs from P values and CIs following the instructions of the Handbook (Higgins 2011).

We sought additional information regarding study details, statistical data, or both, from the authors of 20 studies. We received information from 15 authors. Ten of the authors provided statistical data that had not been published in their articles, which enabled us to include nine of these studies in the meta‐analyses. In the case of two studies the correspondence led to the exclusion of the study because essential information on the primary outcome measure could not be provided (Simon 2000; Stant 2009). Whenever essential information concerning the risk of bias could not be obtained within four weeks of contacting the authors, we listed the corresponding details as 'unclear.'

Assessment of heterogeneity

For clinical heterogeneity, we had the following considerations for similarity or heterogeneity between studies.

We considered interventions to have a similar mechanism and effect in all types of participants.
We considered the effects and mechanisms for all work‐directed interventions as similar.
The three subcategories of clinical interventions, anti‐depressants, psychological interventions or exercise were considered as having different effects and mechanisms.
All various sickness absence outcomes and all various depression outcomes were considered similar.
Follow‐up times of up to two month (short‐term), from over two months to one year (medium‐term) and over one year (long‐term) were considered different.

We assessed statistical heterogeneity in the meta‐analyses with the I² statistic. If we observed considerable heterogeneity (I² > 75%), we refrained from statistical pooling of the studies within that comparison. Substantial inconsistency (I² statistic) also led to downgrading of the certainty of the evidence (see Data synthesis for details).

Assessment of reporting biases

We produced funnel plots for visual inspection of possible publication bias.

Data synthesis

For each predefined comparison, we analyzed data for each outcome measure separately. Whenever interventions belonged to the same category in the comparison but two review authors (KN and JV, or KN and BF) judged them dissimilar, we defined subcategories for these types of intervention. We conducted meta‐analysis if two review authors (KN and BF) judged a group of trials sufficiently homogeneous in terms of participants, interventions, and outcomes to provide a meaningful summary. In such cases, we calculated pooled SMDs for the predefined outcome measures using the Review Manager 5 software (RevMan 2014) with a random‐effects model. We chose a random‐effects model as we expected statistical heterogeneity to occur as a result of the clinical and methodological heterogeneity in research on sickness absence. For three‐armed trials contributing evidence to two different comparisons, we divided the number of participants of the arm used in both comparisons by two.

Subgroup analysis and investigation of heterogeneity

We considered that there could be difference in the way psychological treatment was administered and we compared studies with a personal therapist or in‐person therapy with web‐based or telephone‐based studies without personal guidance of a therapist. In addition, we planned to analyze if studies with mostly women (> 80%) had different effects from studies with mostly men (> 80%). However, we did not include a sufficient number of studies with such an uneven gender‐distribution to allow for this analysis.

Sensitivity analysis

We planned to conduct sensitivity analyses by excluding:

studies with a high risk of bias (defined as at least three of the 'Risk of bias' items were judged to present a low risk of bias: random sequence generation; allocation concealment; blinding of participants/personnel; blinding of outcome assessment;
studies with skewed data; and
studies in which workers were a small subgroup of the study population.

However, the small numbers of studies in each comparison only allowed for the sensitivity analyses of risk of bias and then only in the comparisons with the highest number of studies.

Summary of findings and assessment of the certainty of the evidence

We used the GRADE approach to assess the certainty of a body of evidence regarding the primary outcome category of the comparisons addressed in the review. At the start of the GRADE assessment process, we assumed high certainty for all studies and we downgraded the certainty of the evidence for each comparison by one to three levels depending on the seriousness of the violations in each domain.

To assess the risk of bias for a comparison, we considered the 'Risk of bias' tables for each study in that comparison. We saw items related to selection bias, detection bias, and attrition bias as prerequisites for high certainty. We only considered studies with low risks on these items to have a low risk of bias. For each comparison we considered the risk of bias serious (‐1) if a majority of the evidence in the studies included in the meta‐analysis (in terms of weights) were of low quality. We applied a ‐2 downgrade in cases where the majority of the studies did not have adequate random sequence generation and allocation concealment. For consistency, we considered an I² value of 50% to 75% to indicate substantial inconsistency, which lead us to downgrade (‐1). If the I² value exceeded 75%, we refrained from pooling the results and we analyzed the results for each study separately. Indirectness of the evidence was not an issue in our review as all comparisons in the included studies directly addressed the comparison. For imprecision of results, we judged serious imprecision leading to downgrading (‐1) if a comparison either included a number of fewer than 400 participants or a wide CI around the effect estimate. For a non‐significant effect, we considered a CI to be wide if it included an SMD of both 0 and a moderate effect size (SMD > 0.5 or < ‐0.5). For I a significant effect, we considered a CI to be wide if it included both a small and large effect size (SMD small = ‐0.2 or 0.2; SMD large = 0.8 or ‐0.8). If in addition to a wide CI, the comparison included one study only, we downgraded with two levels (‐2).

The resulting interpretation of the certainty of the level of evidence per comparison was as follows.

High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

We created ‘Summary of Findings’ (SOF) tables with GRADEpro software (GRADEpro 2008) for the main comparisons.

Results

Description of studies

Results of the search

Figure 1 displays a PRISMA study flow chart of the inclusion process up to 2014. Figure 2 displays the flow chart of the 2020 update. The electronic searches between 2014 and 2020 resulted in 5951 new hits. We assessed the titles and abstracts for eligibility. This resulted in the full text assessment of 104 publications. We excluded 82 studies after further scrutiny (see Characteristics of excluded studies). This resulted in the inclusion of 22 new studies additional to the 23 studies already in the review. In addition, we identified five ongoing studies in the first and none in the 2020 update (see Characteristics of ongoing studies).

Figure 1

PRISMA Study flow diagram of the study selection process until 2014.

Figure 2

PRISMA Study flow diagram of the study selection process 2014‐2020.

Included studies

We included 45 studies in the review (see Characteristics of included studies). Four of these studies included three study arms (Kaldo 2018; Kendrick 2005; Knekt 2013; Krogh 2009) and one had four study arms (Finnes 2017). In our analyses we combined two interventions groups of the Kendrick 2005 and two of the Knekt 2013 study. Therefore, in the end we analyzed a total of 93 study arms in this review.

Designs

Of the included studies, 40 were RCTs and five were cluster‐RCTs (Noordik 2013; Rost 2004; Schoenbaum 2001; Björkelund 2018; Volker 2015). Intra‐class correlations for four of these studies were reported to be negligible and therefore we did not adjust the data. However the Björkelund 2018 study did not report the ICC and we therefore adjusted undertook an unplanned sensitivity analysis (see effects of interventions).

Sample sizes

The total number of participants in the included studies was 13,669. The number of participants included in the analysis was lower (12,109) as we reported on the subgroup of 'employed and depressed participants only' in cases where studies included other subgroups as well. The number of participants in the smallest study (sub)group was lower than 50 in 20 study arms, between 50 and 99 in 22 study arms, between 100 and 199 in 23 study arms, and 200 or more in 18 study arms.

Time period, setting and participants

Three studies were published before 2000, 15 between 2000 and 2010, and 27 after 2010. Eight studies were conducted in the US, 34 were conducted in Europe, one in Canada and two in Australia. Participants were recruited in primary care settings (13 studies), outpatient settings (15 studies), workplace settings (five studies), occupational health care (five studies), through health insurance companies (two), a managed care setting (one study), an unemployment centre (one study), a community mental health centre (one study), a hospital (one study), and through an academic institution (one study). In 32 studies, all participants had a depressive disorder. In 13 studies (Bee 2010; Finnes 2017; Hellstrom 2017; Kendrick 2005; Knapstad 2020; Knekt 2013; McCrone 2004; Meuldijk 2015; Noordik 2013; Reme 2015; Reme 2019; Volker 2015; Wormgoor 2020) depressed patients constituted a subgroup of the study participants.

Interventions

Work‐directed interventions, or work‐directed interventions combined with a clinical intervention

We identified 17 work‐directed interventions in 14 studies. Thirteen interventions, reported in 11 studies, were a combination of a work‐directed and a clinical intervention (Finnes 2017; Geraedts 2014; Hees 2013; Kaldo 2018; Lerner 2012; Lerner 2015; Lerner 2020; Reme 2015; Schene 2006; Vlasveld 2013; Volker 2015). Four interventions were work‐directed only (Finnes 2017; Hellstrom 2017; Noordik 2013; Reme 2019).

All four work‐directed interventions included multiple meetings with intervention providers, three specified meetings in the Finnes 2017 study and multiple meetings in the other three. In Noordik 2013, the number depended on the time it took to return to work and the Hellstrom 2017 and Reme 2019 studies provided unlimited support, depending on the individual need of the participants.

The work‐directed interventions in Finnes 2017, Hellstrom 2017 and Noordik 2013 all included contact of the intervention provider with the supervisor of the worker. In the Finnes 2017 study, however, this was most structured as it included a stepwise method with separate worker and supervisor interviews and one convergence meeting with both.

The Noordik 2013 study compared an exposure‐based return to work intervention (RTW‐E) conducted by occupational physicians (OPs), gradually exposing the participants to more demanding work situations, with regular support by the OP. The RTW‐E program provided workers with several homework assignments aimed at preparing, executing, and evaluating an exposure‐based RTW plan. In the Finnes 2017 study, the work‐directed Intervention aimed to facilitate dialogue between the participant and the workplace through a series of steps involving the participant and the nearest supervisor, resulting in a return‐to‐work plan. Providers were either clinical or behavioural psychologists, or psychiatric nurses. In the Hellstrom 2017 study, the intervention followed the Individual Placement and Support (IPS) model. Workers could be out of a job for a longer time (up to three years) and return to work in those workers included return to a new job. The intervention included career counselling and contact with employers to help participants obtain jobs and keep them. Providers were mentors (nurses, social workers or occupational therapists) and career counsellors. In the Reme 2019 study, the intervention also followed the IPS model and included personalised benefits counselling, rapid job search (starting within one month), systematic job development, and time unlimited and individualized support. Providers were employment specialists.

Three of the work‐directed interventions compared that intervention with other work‐directed interventions; in the Hellstrom 2017 study, this included services as offered by the job centres in Denmark, for instance, courses, company internship programmes, wage subsidy jobs, skill development and guidance, mentor support or gradual return to employment. The work‐directed 'care as usual' by OPs in the Noordik 2013 study was based on a national guideline. Care as usual included both work modification and support. In the Reme 2019 study, the work‐directed 'care as usual' involved a referral to either work with assistance by a personal facilitator, and included finding suitable work, negotiating wage and employment conditions, modified duties, and follow‐up at the work place or to a traineeship in a sheltered business. The work‐directed intervention in the Finnes 2017 study was compared to care as usual from a medical doctor.

Of the 13 interventions that combined a work‐directed intervention with a clinical intervention, the main mode of intervention delivery was face‐to‐face meetings in five studies with seven interventions (Finnes 2017; Hees 2013; Reme 2015; Schene 2006; Vlasveld 2013); online in three studies (Geraedts 2014; Kaldo 2018; Volker 2015); and by telephone in three studies (Lerner 2012; Lerner 2015; Lerner 2020). The number of meetings in interventions that included face‐to‐face or telephone meetings ranged from four (Lerner 2012); six to 12 (Vlasveld 2013); eight (Lerner 2015; Lerner 2020); 37 (Hees 2013) to 44 meetings in the Schene 2006 study.

The combined work‐directed and clinical interventions most often based the clinical interventions on cognitive behavioural therapy (CBT) principles (Kaldo 2018; Lerner 2012; Lerner 2015; Lerner 2020; Reme 2015), on the principles of problem‐solving therapy (PST) (Vlasveld 2013) or a combination of CBT and PST (Geraedts 2014; Volker 2015). The clinical part of the Hees 2013 and Schene 2006 studies included psychiatric clinical management according to American Psychiatric Association guidance, which also included antidepressants. The Vlasveld 2013 study also included antidepressant treatment with PST. Finnes 2017 was the only study that used acceptance and commitment therapy (ACT) as the basis for their clinical intervention. The work‐directed interventions ranged from an elaborated and highly structured program provided by occupational therapists in the Hees 2013 and Schene 2006 studies, through facilitating dialogue between the participant and the workplace in three meetings in the Finnes 2017 study, and work‐directed care modelled after Individual Placement and Support (IPS) in the Reme 2015 study.

Providers of the clinical part of the interventions were psychiatric residents in the Hees 2013 and Schene 2006 studies, clinical psychologists in the Finnes 2017 and Reme 2015 studies, counsellors in the Lerner 2012 and Lerner 2015 studies, occupational physicians in the Vlasveld 2013 study, The web‐based clinical interventions included support from a psychology student in the Geraedts 2014 study, support from an occupational physician in the Volker 2015 study, and support from clinical psychologists or supervised psychology students in the Kaldo 2018 study.

The work‐directed part of the intervention was delivered by the same providers in the Geraedts 2014, Kaldo 2018, Lerner 2012, Lerner 2015, Vlasveld 2013, and Volker 2015 studies. The work‐directed part of the intervention was delivered by another provider in the Finnes 2017 study (clinical psychologist, behavioural therapist, or psychiatric nurse), the Hees 2013 and Schene 2006 studies (occupational therapist), the Lerner 2020 study (doctoral‐level psychologist) and the Reme 2015 study (employment specialist).

Two studies combining a work‐directed intervention with a clinical intervention employed multiple comparisons. In the Finnes 2017 study, comparisons were 1) the work‐directed component only, 2) the clinical component only, and 3) care as usual provided by access to a medical doctor, psychologist, social worker, physical therapist, or nurse). Kaldo 2018 used both exercise (aerobic) and care as usual (primary care standard treatment for depression determined by the patient’s general practitioner) as comparisons.

The Hees 2013 and Schene 2006 studies compared the work‐directed intervention combined with a clinical intervention with the clinical intervention alone, whereas the Reme 2015, Vlasveld 2013, and Volker 2015 studies used the work‐directed intervention alone as the comparison.

Three studies compared the work‐directed intervention combined with a clinical intervention to care as usual which could include various providers, but these were not specified (Lerner 2012; Lerner 2015; Geraedts 2014) or included a team of various providers (Lerner 2020; psychologists, nurses and social workers).

Clinical interventions

We included 31 studies reporting the effects of clinical interventions for depressed workers.

Psychological interventions

Twelve studies assessed the effect of a psychological intervention (Bee 2010; Beiwinkel 2017; Birney 2016; Eriksson 2017; Finnes 2017; Hollinghurst 2010; Kendrick 2005; Knekt 2013; Mackenzie 2014; McCrone 2004; Phillips 2014; Wormgoor 2020). Four of these studies looked at an intervention that was delivered face‐to‐face (Finnes 2017; Kendrick 2005; Knekt 2013; Wormgoor 2020). One intervention was delivered by telephone only (Bee 2010); one offered telephone guidance alongside an online intervention (Eriksson 2017); and three studied an online intervention and provided guidance through text messages with a provider (Beiwinkel 2017; Hollinghurst 2010; Mackenzie 2014). A further three were online programmes delivered without guidance (Birney 2016; McCrone 2004; Phillips 2014). The intensity of these interventions varied from five or six sessions (Finnes 2017; Mackenzie 2014; Phillips 2014), eight (Kendrick 2005; McCrone 2004), ten (Hollinghurst 2010) and 12 sessions (Bee 2010; Beiwinkel 2017) to 20 sessions or more (Knekt 2013; Wormgoor 2020). In two studies, the number of sessions was not specified (Birney 2016; Eriksson 2017).

Eight of the 12 interventions were based on the principles of CBT. One was based on ACT (Finnes 2017); one was based on PST (Kendrick 2005); one was based oThank n psychodynamic therapy (Knekt 2013), and one focused on normalisation and coping (Wormgoor 2020).

Intervention providers were clinical psychologists in the ACT arm of the Finnes 2017 study. Beiwinkel 2017 and Eriksson 2017 used both psychologists and psychotherapists to provide guidance alongside the online CBT, while the psychotherapy intervention in Knekt 2013 study, and the coping‐focussed therapy in Wormgoor 2020 were delivered by psychotherapists alone. The telephone CBT was provided by mental health workers in Bee 2010 and mental health specialists provided the email guidance alongside the online CBT in the Mackenzie 2014 study. In Kendrick 2005, the intervention was delivered by community mental health nurses.

Six studies (Bee 2010; Eriksson 2017; Finnes 2017; Hollinghurst 2010; Kendrick 2005; McCrone 2004) compared their intervention with care as usual in general practice.

Three studies compared their online interventions to directing workers with text based information on depression (Beiwinkel 2017; Birney 2016; Phillips 2014). The Knekt 2013 study compared psychodynamic psychotherapy with PST and Wormgoor 2020 compared their coping focused therapy to brief psychotherapy. The online CBT in the Mackenzie 2014 study was compared with a waiting list condition.

Psychological interventions plus antidepressant medication

Two studies included interventions with a combination of psychological interventions and antidepressant medication. One study (Burnand 2002) compared the effect of psychodynamic therapy combined with TCA medication with TCA medication alone. The intervention included face‐to‐face individual sessions by a nurse combined with clomipramine for a duration of 10 weeks. The frequency of the psychotherapy sessions was not fixed. This was compared with a group receiving the same medication and who received supportive care (an individual session with empathic listening, guidance, and support). One study (Sarfati 2016) compared a combination of SSRI medication and a telephone‐administered CBT programme with medication and adherence enhancing phone calls. The CBT programme included eight 30‐minutes sessions provided by PhD‐ or Master’s degree‐level experienced therapists. In the control condition, a research coordinator provided a 10‐minute structured telephone call weekly for eight weeks, with enquiry about progress and reminders to take medication properly

Antidepressant medication

Six studies examined the effectiveness of antidepressant medication, of which one compared the antidepressant medication with a placebo condition (Agosti 1991) and the other five with another antidepressant medication (Fantino 2007; Fernandez 2005; Miller 1998; Romeo 2004; Wade 2008). Three studies compared a SSRI with SNRI medication (Fernandez 2005; Romeo 2004; Wade 2008), one study compared a SSRI with TCA (Miller 1998), one study compared two different SSRIs (Fantino 2007), and one study compared TCA or MAO inhibitors with placebo (Agosti 1991).

Improved care

Eight studies (Björkelund 2018; Knapstad 2020; Meuldijk 2015; Rost 2004; Schoenbaum 2001; Simon 1998; Wang 2007; Wikberg 2017) looked at the effects of improving care management for depressed workers rather than evaluating one specific clinical intervention.

Five studies (Björkelund 2018; Rost 2004; Schoenbaum 2001; Simon 1998; Wikberg 2017) compared enhanced primary care with primary care as usual. In these types of interventions general practitioners were enrolled in a quality improvement program and were expected to provide enhanced care including antidepressant medication and psychological interventions, according to primary care guidelines. In the Björkelund 2018 study, this included a nurse acting as a care manager to assist the general practitioner in providing care. The care manager would have one face‐to‐face meeting and five to seven follow‐up meetings by telephone. In the Wikberg 2017 study, general practitioners were taught how to use the MADRS‐S to monitor changes in depressive symptoms. Workers made four visits to the general practitioner before which the worker completed the MADRS‐S.

One study (Wang 2007) compared a structured telephone outreach and care management program with usual managed care. Workers were enrolled after screening offered to various work organisations that took part in a managed behavioural health care program. The telephone outreach systematically assessed needs for treatment, facilitated entry into in‐person treatment (both psychotherapy and antidepressant medication), monitored and supported treatment adherence, and (for those declining in‐person treatment) provided a structured psychotherapy intervention by telephone. Intervention participants declining in‐person treatment and experiencing significant depressive symptoms after two months were offered a structured eight‐session cognitive behavioural psychotherapy program.

In the Meuldijk 2015 study, concise and protocolised psychotherapy and pharmacotherapy care were provided within seven weeks and compared with psychotherapy and pharmacotherapy that was provided without limitations to the number of sessions. In the Knapstad 2020 study, Prompt Mental HealthCare (PMHC) was provided as part of primary care. This meant that clients could directly contact PMHC and have access to mental health treatment (within 48 hrs).

Exercise

Three exercise interventions were included; strength training (Krogh 2009), aerobic training (Krogh 2009; Krogh 2012) or a program including either light, moderate or vigorous exercise (Kaldo 2018).

The exercise interventions were compared with relaxation (Krogh 2009; Krogh 2012) or standard treatment for depression determined by the patient’s general practitioner (Kaldo 2018).

Art

In the Blomdahl 2018 study, a protocolised art therapy was compared with care as usual, which could include acupuncture, cognitive–behavioural therapy, electroconvulsive therapy, interpersonal therapy, occupational therapy, pharmacological therapy, physiotherapy, psychodynamic therapy,and supportive therapy.

Diet

The Chatterton 2018 study assessed the effect of a dietary intervention comprising of personalised dietary advice and nutritional counselling support, including motivational interviewing, goal setting and mindful eating, from a clinical dietician in order to support optimal adherence to the recommended diet. The dietary intervention was compared with a social support control group in which trained personnel befriended participants by discussing neutral topics of interest to the participant, such as sport, news or music.

Outcomes

Studies were only selected if they reported on sickness absence. Of the 45 included studies, seven studies (Agosti 1991; Bee 2010; Krogh 2012; Miller 1998; Schene 2006; Wang 2007; Lerner 2020) reported days or hours worked instead of days of sickness absence. These measures were transformed into sickness absence days as described in the 'Methods' section (see Measures of treatment effect).

We were able to collect data on depression for all but five of the included studies (Agosti 1991; Kaldo 2018; Mackenzie 2014; Meuldijk 2015; Volker 2015). Of all studies reporting on depression, one study (Schoenbaum 2001) presented only dichotomous depression data while all others presented continuous data.

Nine studies (Agosti 1991; Burnand 2002; Hees 2013; Lerner 2012; Lerner 2020; Miller 1998; Rost 2004; Wade 2008; Wang 2007) reported on work functioning using a (sub)scale that separately measured work instead of work and other activities combined. The SD's around the mean scores for work functioning could not be retrieved in the Rost 2004 study, therefore this outcome was not included in the meta‐analysis.

Two studies reported on work ability (Finnes 2017; Kaldo 2018) another study reported on both work functioning and work ability (Sarfati 2016).

Ten studies (Geraedts 2014; Hellstrom 2017; Kaldo 2018; Knapstad 2020; Krogh 2012; Reme 2015; Reme 2019; Schoenbaum 2001; Wade 2008; Wormgoor 2020) reported on 'not working' or 'working' or sickness absence status at the end of follow up. We recalculated all outcomes so that they represent the proportion of workers off work at follow‐up. The Schoenbaum 2001 study presented only % of those employed at baseline, and these baseline numbers for the total group. The actual numbers of participants at work was calculated bases on the assumption of an equal distribution of baseline employment between study arms. The Blomdahl 2018 reported on a % of workers with sickness absence during follow‐up.

Follow up

(a) Short‐term

Four of the included studies had the last outcome measurement within one month Agosti 1991; Birney 2016; Fantino 2007; Fernandez 2005).

(b) Medium‐term

In 32 studies, the last follow‐up measurement was between one month and a year after inclusion. Five studies had the last follow‐up measurement later than one year but provided data on earlier time points as well (Hees 2013; Hellstrom 2017; Knekt 2013; Rost 2004; Schene 2006). We included these outcomes in the medium‐term analysis. We used the last available observation within the first year for this purpose.

(c) Long‐term

In nine studies, the last follow‐up measurement was later than one year after inclusion, of which three reported on a follow‐up period of 18 months (Hees 2013; Reme 2015; Reme 2019), four on 24 months (Hellstrom 2017; Rost 2004; Schoenbaum 2001; Wormgoor 2020), one on 42 months (Schene 2006), and one on five years (Knekt 2013). However, only depression data and not sickness absence days were reported at two years in the Schoenbaum 2001 study. We therefore refrained from using the depression data at this time point, leaving six studies with long‐term outcome data.

Excluded studies

We excluded a total of 82 studies from the review. Reasons for excluding studies were:

sickness absence not measured as an outcome (Aasvik 2017; Ahola 2012; Amore 2001; Barbui 2009; Bejerholm 2017; Boyer 1998; Brandes 2011; Carlin 2010; Castillo‐Pérez 2010; Dalgaard 2014; Danielsson 2019; Dean 2017; Dunlop 2011; Endicott 2014; Erkkilä 2011; Finley 2003; Fournier 2015; Han 2015; Hirani 2010; Hobart 2019; Hollon 2016; Johansson 2019; Kennedy 2016; Kennedy 2019; Knekt 2016; Kojima 2010; Kroenke 2001; Kuhs 1996; Lam 2012; Löbner 2018; Martinez 2011; Meyer 2009; Mundt 2001; Oakes 2012; Salminen 2008; Saloheimo 2016; Sandahl 2011; Shawyer 2016; Simon 2000; Sir 2005; Soares 2019; Stant 2009; Zwerenz 2017);
participants had a mild depressive disorder or were not diagnosed with a depressive disorder (Aasdahl 2017; Aasdahl 2018; Aelfers 2013; Arends 2014; Bakker 2007; Becker 1998; Bejerholm 2015; Blonk 2007; Brouwers 2007; Dalgaard 2017; Dalgaard 2017a; Ebert 2014; Furukawa 2012; Hackett 1987; Jansson 2015; Lagerveld 2012; Lexis 2011; Mino 2006; Morgan 2011; Reavley 2018; Salomonsson 2017; Warmerdam 2007; Zeeuw 2010; Zwerenz 2017a);
not a RCT design (Bech 2000; Eklund 2012; Evans 2016; Knekt 2011; Schmitt 2008; Wisenthal 2018; Zambori 2002);
no worker population (Alexopoulos 2011; Folke 2012; Forman 2012; Gunnarson 2018; Twamley 2019);
study took place in an inpatient care setting (Dick 1985; Hordern 1964);
not able to define a subgroup of depressed patients (Beurden 2013; Gournay 1995);
a double publication (deVries 2015; Maljanen 2016; Schoenbaum 2002; Wells 2000; Winter 2015);
publication was a study protocol (Dean 2014; Ebert 2014a; Eisendrath 2014; Kooistra 2014; Zwerenz 2015);
study was prematurely terminated because of massive reorganizations and reimbursement changes in mental health care in the Netherlands during the study period (Heer 2013).

Studies awaiting assessment

There are four ongoing studies that have not reported yet: Deady 2018; Imamura 2018; Kouvonen 2019; Poulsen 2017

Risk of bias in included studies

In Figure 3 and Figure 4 an overview of the risk of bias per study is presented. For details see the 'Risk of bias' tables that form part of the Characteristics of included studies.

Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 4

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

The method for generating random numbers posed a low risk of bias in 36 studies and was unclear in nine.

In three cluster‐RCTs (Noordik 2013; Rost 2004; Schoenbaum 2001) allocation concealment was not adequate, which was probably indicative of the non‐feasibility of allocation concealment in this type of design. In seven further studies (Agosti 1991; Björkelund 2018; Burnand 2002; Lerner 2015; Mackenzie 2014; Miller 1998; Wikberg 2017) information on allocation concealment could not be retrieved, leading to a judgment of unclear risk of bias. In 35 studies, the allocation concealment was adequate and therefore posed a low risk of bias.

Blinding

Risk of performance bias was low in studies using a double‐blind design (blinding of participant and care provider). This design was feasible in studies comparing the occupational health effects of antidepressant medications. This type of study has a low risk of performance bias (Agosti 1991; Fantino 2007; Fernandez 2005; Miller 1998; Romeo 2004; Wade 2008). In other clinical interventions, such as psychological or exercise interventions and in work‐directed interventions, blinding of the participant or care provider was not feasible. However, we considered the risk of performance bias high only in those studies where the control intervention could be considered less desirable by participants or care provider (Bee 2010; Beiwinkel 2017;Chatterton 2018;Hollinghurst 2010; Kendrick 2005; Knapstad 2020; Krogh 2009; Mackenzie 2014; McCrone 2004; Reme 2019; Sarfati 2016).

Our primary outcome measure (sickness absence days) could be measured either by self‐report or retrieval from attendance records and national registries. In the case of self‐report, the outcome could be biased by unblinded participants’ knowledge of the intervention. In 27 studies we considered the risk of detection bias to be high. With regard to the secondary outcome depression, 31 studies had a high risk of bias, and for two studies the risk was unclear. Our secondary outcome work functioning was measured in 11studies only. For reasons of clarity of the risk of bias table, the findings for this outcome were reported in Table 1.

Open in table viewer

Table 1. Work functioning outcome: Risk of bias

Study	Blinding of outcome assessment (detection bias)	Incomplete outcome data: attrition bias
Agosti 1991	Low risk (blinded clinician)	High risk
Burnand 2002	High risk (self‐report)	High risk
Finnes 2017	High risk (self‐report)	Low risk
Hees 2013	High risk (self‐report)	Low risk
Kaldo 2018	High risk (self‐report)	High risk
Knekt 2013	High risk (self‐report)	Low risk
Lerner 2012	High risk (self‐report)	Low risk
Miller 1998	High risk (self‐report)	Unclear risk
Sarfati 2016	High risk (self‐report)	High risk
Wang 2007	High risk (self‐report)	Low risk
Lerner 2020	High risk (self‐report)	Low risk

Incomplete outcome data

We found nine of the 45 studies to have a low risk of attrition bias for both sickness absence and depressive symptoms, and 15 studies with a high risk of attrition bias for both outcomes, the other 21 studies showed different levels of risk of bias for sickness absence and depressive symptoms or had an unclear risk of attrition bias for either or both outcomes. Studies with attrition between 10% and 20% could still be classified as having low risk of attrition bias if adequate analyses were conducted to take selective attrition into account. Examples of such analyses are multiple imputation methods or sensitivity analyses. Our secondary outcome work functioning was measured in only 11 studies in a way that the findings could be included in the meta‐analyses. To maintain clarity in the 'Risk of bias' table, we reported the findings for this outcome in Table 1.

Selective reporting

For 23 studies, no design paper or trial registration could be identified in order to assess the risk of selective reporting. In 15 studies we considered the risk to be low (Beiwinkel 2017; Chatterton 2018; Eriksson 2017; Geraedts 2014; Hees 2013; Hellstrom 2017; Kendrick 2005; Knapstad 2020; Lerner 2015; Lerner 2020; Meuldijk 2015; Phillips 2014; Reme 2015; Reme 2019; Vlasveld 2013). In seven studies, the risk of reporting bias was deemed high, in the Björkelund 2018 study the trial was retrospectively registered. In Mackenzie 2014 and Kaldo 2018, the trial protocol was retrospectively registered and work participation was not mentioned as an outcome. In Krogh 2009, no report was made regarding the third treatment group (relaxation) in the study protocol. In the protocol of the Sarfati 2016 study, an assessment at 6 months is announced, but this is not reported. In the Noordik 2013 study, an outcome measure that was presented in the study design was not reported as an outcome. In Volker 2015, the inclusion criteria reported in the protocol changed from depressive disorders to common mental disorders as a result of a new sponsor after years of inclusion. Also, more outcomes were added.

Other potential sources of bias

We identified other sources of bias in four studies. In Birney 2016, we identified a potential conflict of interest, as the study’s principal investigator may have had financial benefit from sales of the intervention. In Kaldo 2018, an unplanned subgroup analysis was conducted and in Mackenzie 2014 the work outcomes were unplanned. In Volker 2015, one occupational physician from the control condition was replaced by another occupational health physician, who then was allocated to the intervention condition.

Effects of interventions

See: Summary of findings 1 Work‐directed plus clinical intervention compared to care as usual in depressed people, medium‐term follow‐up; Summary of findings 2 Work‐directed intervention compared to care as usual in depressed people, medium‐term follow‐up; Summary of findings 3 Psychological intervention compared to care as usual in depressed people, medium‐term follow‐up; Summary of findings 4 Improved care compared to care as usual in depressed people, medium‐term follow‐up

Below we present the results for our primary outcome, sickness absence, for each of the comparisons. We present our secondary outcomes, depressive symptoms and work functioning, for each of the work‐directed interventions as well.

1. Work‐directed interventions

1.1 Work‐directed plus clinical intervention compared to care as usual (medium‐term follow‐up)

Eleven studies examined the effect of combining a work‐directed intervention with a clinical intervention in comparison to various care as usual conditions (Finnes 2017; Geraedts 2014; Hees 2013; Kaldo 2018; Lerner 2012; Lerner 2015; Lerner 2020; Reme 2015; Schene 2006; Vlasveld 2013; Volker 2015). Nine of these studies reported on sickness absence days, while two (Kaldo 2018; Reme 2015) reported on whether workers were off work (yes or no). The pooled results of nine studies revealed that work‐directed interventions combined with a clinical intervention led to fewer sickness absence days in comparison with care as usual (SMD ‐0.25, 95% CI ‐0.38 to ‐0.12; Analysis 1.1). A sensitivity analysis showed that removing the study with a higher risk of bias (Lerner 2015) did not substantially change this outcome (SMD ‐0.24, 95% CI ‐0.41 to ‐0.08; Analysis 19.1).

No difference in being off work was found between work‐directed and clinical interventions compared to care as usual (RR 1.08, 95% CI 0.64 to 1.83; Analysis 1.2).

Eight studies (Finnes 2017; Geraedts 2014; Hees 2013; Lerner 2012; Lerner 2015; Lerner 2020; Schene 2006; Vlasveld 2013) also reported on depressive symptoms. The summarised results of these studies showed that a work‐directed interventions combined with a clinical intervention led to lower levels of depressive symptoms (SMD ‐0.25, 95% CI ‐0.49 to ‐0.01; Analysis 1.3).

Work functioning outcomes were reported in five studies (Finnes 2017; Hees 2013; Kaldo 2018; Lerner 2012; Lerner 2020). The summarised results of these studies did not show a difference in work functioning between the two conditions (SMD ‐0.19, 95% CI ‐0.43 to 0.06; Analysis 1.4)

As this comparison comprised various usual care conditions, we present the subgroup results of the primary outcome for each condition separately below.

1.1.1 Work‐directed plus clinical interventions compared to care as usual (psychiatric clinical management)

Two studies examined the effectiveness of a work‐directed intervention combined with a clinical intervention (psychiatric clinical management) in comparison to a psychiatric clinical management alone (Hees 2013; Schene 2006). The summarised effect of the two studies which added occupational therapy to psychiatric clinical management on sickness absence days was not statistically significant (SMD ‐0.30, 95% CI ‐0.61 to 0.01). The combined results of these two studies showed no difference between the interventions in effect on depressive symptoms (SMD ‐0.08, 95% CI ‐0.66 to 0.50), nor did the Hees 2013 study find an effect on work functioning (SMD ‐0.09, 95% CI ‐0.48 to 0.29).

1.1.2 Work‐directed plus clinical interventions compared to care as usual (primary care)

Five studies compared the effect of a work‐directed plus clinical intervention with care as usual consisting of access to primary care, of which four (Finnes 2017; Lerner 2012; Lerner 2015; Lerner 2020) measured sickness absence days and one (Kaldo 2018) investigated the number of workers on sickness absence. The pooled effect of the four studies showed that a work‐directed plus clinical intervention reduced the number of sickness absence days (SMD ‐0.32, 95% CI ‐0.56 to ‐0.07) but the Kaldo 2018 study did not find a difference in number of workers off work (RR 1.73, 95% CI 0.70 to 4.24) between the two conditions.

1.1.3 Work‐directed plus clinical interventions compared to care as usual (work‐directed interventions)

Three studies (Reme 2015; Vlasveld 2013; Volker 2015) compared the effect of a work‐directed plus clinical intervention with care as usual consisting of work‐directed interventions, such as usual occupational healthcare or employment services. Two of these studies (Vlasveld 2013; Volker 2015) measured sickness absence days and one (Reme 2015 examined the number of workers off work. The pooled effect of the two studies showed no difference on sickness absence days (SMD ‐0.20, 95% CI ‐0.44 to 0.04), and the Reme 2015 study did not find a difference in number of workers off work (RR 0.94, 95% CI 0.83 to 1.06) between the two conditions.

1.1.4 Work‐directed plus clinical interventions compared to care as usual (no intervention)

One study (Geraedts 2014) compared the effect of a work‐directed intervention with no intervention and found no effect on sickness absence days between the two conditions (SMD 0.02, 95% CI ‐0.33 to 0.37).

1.2 Work‐directed plus clinical intervention compared to care as usual (long‐term follow‐up)

Two studies also reported long‐term effects of (Hees 2013; Schene 2006) of their work‐directed clinical intervention. These two studies found that in the long term, a work‐directed intervention plus clinical intervention did not reduce sickness absence days in comparison with care as usual (SMD ‐0.19; 95% CI: ‐0.49 to 0.12; Analysis 2.1). However, one of the two studies (Hees 2013) found that the work‐directed intervention reduced depressive symptoms in the long term (SMD ‐0.63; 95% CI ‐1.02 to ‐0.24;Analysis 2.2). That same study did not find an effect on work functioning (SMD ‐0.25, 95% CI ‐0.63 to 0.14;Analysis 2.3).

1.3 Work‐directed plus clinical intervention compared to psychological intervention (medium‐term follow‐up)

One study (Finnes 2017) compared the effect of a work‐directed intervention (facilitating a dialogue between the participant and the supervisor following a protocol) combined with a clinical intervention (Acceptance and Commitment Therapy) with the clinical intervention alone. This study did not find differences between the two intervention in terms of sickness absence days (SMD 0.04, 95% CI ‐0.47 to 0.56;Analysis 3.1), depressive symptoms(SMD ‐0.15, 95% CI ‐0.69 to 0.39; Analysis 3.2), nor work functioning (SMD ‐0.08, 95% CI ‐0.63 to 0.48;Analysis 3.3).

1.4 Work‐directed plus clinical intervention compared to work‐directed intervention (medium‐term follow‐up)

The Finnes 2017 study also compared the effect of a work‐directed intervention (facilitating a dialogue between the participant and the supervisor following a protocol) combined with a clinical intervention (Acceptance and Commitment Therapy) to the work‐directed intervention alone.This study did not find differences between the two intervention in terms of sickness absence days (SMD ‐0.10, 95% CI ‐0.65 to 0.45;Analysis 4.1), depressive symptoms (SMD ‐0.37, 95% CI ‐0.98 to 0.23;Analysis 4.2), nor work functioning (SMD 0.32, 95% CI ‐0.30 to 0.94;Analysis 4.3).

1.5 Work‐directed intervention compared to care as usual (medium‐term follow‐up)

Four studies (Finnes 2017; Hellstrom 2017; Noordik 2013; Reme 2019) compared a work‐directed intervention with care as usual. Two of these (Finnes 2017; Noordik 2013) reported sickness absence days, while two other (Hellstrom 2017; Reme 2019) reported the number of workers off work. Of the Reme 2019 study only the long‐term result were retrieved from the authors (see comparison 1.6). In three studies (Hellstrom 2017; Noordik 2013; Reme 2019), care as usual was work‐directed, such as regular occupational healthcare or employment services. In the Finnes 2017 study, a work‐directed intervention was compared to primary care as the care as usual condition.

The combined effect of the Finnes 2017 and Noordik 2013 studies showed workers in the care as usual condition had less sickness absence days compared to workers who received the work‐directed intervention (SMD 0.39, 95% CI 0.04 to 0.74;Analysis 5.1). The Hellstrom 2017 study did not find an effect on the number of workers off work (RR 0.93, 95% CI 0.77 to 1.11;Analysis 5.2).

The results of all four studies combined showed no effect on depressive symptoms (SMD ‐0.10, 95% CI ‐0.30 to 0.10; Analysis 5.3). Finnes 2017 was the only study in this comparison that reported work functioning, and did not find a difference between the work‐directed intervention and usual care(SMD ‐0.32, 95% CI ‐0.90 to 0.26;Analysis 5.4).

1.6 Work‐directed intervention compared to care as usual (long‐term)

Of the studies that compared a work‐directed intervention with care as usual, two studies (Hellstrom 2017; Reme 2019) reported long‐term outcomes. The combined results of these studies found no effect on the number of workers off work (RR 1.00, 95% CI 0.82 to 1.22; Analysis 6.1), and the Hellstrom 2017 study did not find a difference in depressive symptoms (SMD 0.18, 95% CI ‐0.13 to 0.49; Analysis 6.2).

2. Clinical interventions

2.1 Psychological intervention compared to care as usual (short‐term follow‐up)

One study (Birney 2016) reported the short‐term outcomes of a psychological intervention, unguided Internet‐delivered therapy and did not find a difference in sickness absence days between the two conditions (SMD ‐0.05, 95% CI ‐0.28 to 0.17; Analysis 7.1).

2.2 Psychological intervention versus care as usual (medium‐term follow‐up)

Nine studies (Bee 2010; Beiwinkel 2017; Birney 2016; Eriksson 2017; Finnes 2017; Hollinghurst 2010; Mackenzie 2014; McCrone 2004; Phillips 2014) compared a psychological intervention, either face‐to‐face, or an E‐mental health intervention with or without guidance from a care provider, with care as usual. These psychological interventions led to a smaller number of sickness absence days (SMD ‐0.15, 95% CI ‐0.28 to ‐0.03; Analysis 8.1). A sensitivity analysis showed that studies with a higher and lower risk of bias did not differ in their effect on days of sickness absence (test for subgroup differences: Chi² = 0.00, df = 1 (P = 1.00); Analysis 20.1).

All these studies, except for Mackenzie 2014, also reported on depressive symptoms. The pooled results of these studies showed that the psychological interventions reduced depressive symptoms (SMD ‐0.30, 95% CI ‐0.45 to ‐0.15; Analysis 8.2).

Only the Finnes 2017 study reported on work functioning and found no difference in this outcome between the psychological intervention and care as usual (SMD 0.05, 95% CI ‐0.46 to 0.57).

2.3 Psychological intervention compared to other psychological intervention (medium‐term follow‐up)

One study (Knekt 2013) with three treatment arms evaluated the effect of alternative psychological interventions. Two study arms assessed psychodynamic therapy, where one study arm examined short‐term and the other long‐term therapy. Both were compared with solution‐focused therapy, but did not lead to fewer sickness absence days (SMD 0.70, 95% CI ‐0.19 to 1.59; Analysis 9.1).

One other study (Wormgoor 2020) compared two alternative psychological interventions and found no difference in the risk of being off work between coping focussed therapy and short‐term psychotherapy in the first year of follow‐up (RR 1.83, 95% CI 1.00 to 3.37; Analysis 9.2).

The Knekt 2013 study also reported on depressive symptoms, but the inconsistency (I²) in this meta‐analysis was 99.2%, we therefore refrained from pooling the results of the two psychodynamic therapy conditions for this outcome. Workers receiving short‐term psychodynamic therapy had less depressive symptoms than workers who received solution‐focused therapy (SMD ‐1.19, 95% CI ‐1.58 to ‐0.81) but workers who received long‐term psychodynamic therapy had more depressive symptoms than workers receiving solution‐focused therapy (SMD 2.04, 95% CI 1.62 to 2.45; Analysis 9.4).

The Knekt 2013 study also reported on work functioning, but the inconsistency (I²) in this meta‐analysis was 97.5%. We therefore also refrained from pooling the results of the two psychodynamic therapy conditions for this outcome. Workers receiving short‐term psychodynamic therapy had fewer work functioning problems than workers who received solution‐focused therapy (SMD ‐0.66, 95% CI ‐1.03 to ‐0.30) but workers who received long‐term psychodynamic therapy had more work functioning problems than workers receiving solution‐focused therapy (SMD 1.00, 95% CI 0.63 to 1.36; Analysis 9.3).

2.4 Psychological intervention compared to other psychological intervention (long‐term follow‐up)

The Knekt 2013 study also had long‐term results (five‐year follow up). We refrained from statistically pooling the results due to high inconsistency (I² = 96.2%). The separate analyses showed that long‐term (SMD ‐4.61, 95% CI ‐5.84 to ‐3.39) and short‐term (SMD ‐0.91, 95% CI ‐1.62 to ‐0.19) psychodynamic psychotherapy reduced sickness absence days more than solution‐focused therapy in the long term (Analysis 10.1).

The Knekt 2013 study also reported on the long‐term depressive symptoms, but the inconsistency (I²) in this meta‐analysis was 92.4%, we therefore refrained from pooling the results of the two psychodynamic therapy conditions for this outcome. Workers receiving short‐term psychodynamic therapy had less depressive symptoms than workers who received solution‐focused therapy (SMD ‐0.91, 95% CI ‐1.62 to ‐0.19) and the same was found for workers who received long‐term psychodynamic therapy (SMD ‐4.61, 95% CI ‐5.84 to ‐3.39). See Analysis 10.3.

The Knekt 2013 study also reported work functioning in the long term, the pooled results of both psychodynamic therapy conditions showed that workers receiving this therapy did not have better work functioning compared to workers receiving solution‐focused therapy (SMD ‐0.26, 95% CI ‐0.52 to 0.01; Analysis 10.4).

The Wormgoor 2020 study also reported the outcome after two years and found no difference in the risk of being off work between coping focused therapy and short‐term psychotherapy at that time (RR 1.14, 95% CI 0.61 to 2.11); Analysis 10.2). The Wormgoor 2020 study also found no difference in depressive symptoms (SMD ‐0.32, 95% CI ‐0.66 to 0.01; Analysis 10.3)

2.5 Psychological intervention with antidepressant compared to antidepressant (medium‐term follow‐up)

Two studies (Burnand 2002; Sarfati 2016) compared the effect of a psychological intervention combined with antidepressants to that antidepressant alone. The Burnand 2002 study combined psychodynamic therapy with TCA medication and the Sarfati 2016 study combined telephone‐administered CBT with a SSRI. The pooled results show no difference in the number of sickness absence days (SMD ‐0.38, 95% CI ‐0.99 to 0.24; Analysis 11.1).

Both studies also reported on depressive symptoms and on work functioning. The pooled results showed no difference in depressive symptoms (SMD ‐0.19, 95% CI ‐0.50 to 0.12; Analysis 11.2) nor work functioning problems (SMD ‐0.24, 95% CI ‐0.68 to 0.20; Analysis 11.3) between the two conditions.

2.6 Any antidepressant medication versus placebo

One study compared a TCA or MAO with placebo (Agosti 1991). That study found no difference in sickness absence days between the antidepressant medication and placebo, the effect may even have been in favour of the placebo condition (SMD 0.48; 95% CI ‐0.05 to 1.00) but this was not statistically significant (Analysis 12.1).

Measured with the work functioning subscale of the LIFE interview, Agosti 1991 did find a statistically significant positive effect in favour of antidepressant medication (SMD ‐0.58; 95% CI ‐1.11 to ‐0.05; Analysis 12.2).

2.7 Antidepressant medication compared to any other antidepressant medication (medium‐term follow‐up)

2.7.1 SSRI versus SNRI

Three studies compared a SSRI with SNRI in depressed workers (Fernandez 2005; Romeo 2004; Wade 2008). In the meta‐analysis, the inconsistency of results between these three studies (I²) was 83% and so we refrained from pooling the results. The results of the single studies were highly inconsistent. We found no difference in sickness absence between a SSRI and SNRI in the Fernandez 2005 study (SMD ‐0.03; 95% CI ‐0.37 to 0.31) as well as in the Romeo 2004 study (SMD 0.28; 95% CI ‐0.13 to 0.69). The Wade 2008 study revealed evidence of an effect on sickness absence favouring a SSRI (SMD ‐0.57; 95% CI ‐0.88 to ‐0.26; Analysis 13.1). Measured with the Sheehan disability scale, this study also reported a favourable effect on work functioning (difference of 2.4; 95% CI 0.4 to 4.1) but the reported data did not allow for inclusion in the meta‐analysis.

2.7.2 SSRI versus TCA

Miller 1998 was the only study comparing an SSRI with TCA medication in depressed workers. This study found no difference between a SSRI and TCA in reducing sickness absence days (SMD 0.08; 95% CI ‐0.08 to 0.25; Analysis 13.1).

The Miller 1998 study measured work functioning using the SAS work composite (Wells 1989). A higher score on this measure reflects a higher level of impairment. The study reported no significant difference on work functioning between the groups (difference of ‐0.08; 95% CI ‐0.24 to 0.09; Analysis 13.3).

2.7.3 SSRI versus SSRI

One study (Fantino 2007) compared one SSRI with another SSRI. This study found evidence of a greater reduction in sickness absence days with escitalopram compared to citalopram (SMD ‐0.31; 95% CI ‐0.54 to ‐0.07; Analysis 13.1.). No difference in depressive symptoms were found between the two interventions (SMD ‐0.23, 95% CI ‐0.47 to 0.00; Analysis 13.2).

2.8 Improved care compared to care as usual (medium‐term follow‐up)

Eight studies (Björkelund 2018; Kendrick 2005; Knapstad 2020; Meuldijk 2015; Schoenbaum 2001; Simon 1998; Wang 2007; Wikberg 2017), one of which had three study arms (Kendrick 2005), examined the effects of improved care management compared with care as usual. For the Meuldijk 2015 study, no data for the depressed subgroup be retrieved from the authors. The pooled results of the seven studies that measured sickness absence days, showed that care management did not lead to fewer sickness absence days (SMD ‐0.05, 95% CI ‐0.16 to 0.06); Analysis 14.1), however the sensitivity analysis revealed a statistically significant difference between the studies with a lower and higher risk of bias (test for subgroup differences: Chi² = 6.00, df = 1 (P = 0.01). The studies with a lower risk of bias (Simon 1998; Wang 2007) did show fewer sickness absence days in the care management condition (SMD ‐0.20, 95% CI ‐0.35 to ‐0.05; Analysis 21.1). A further sensitivity analysis showed that the results for all studies pooled together minus the one with a cluster‐randomised design (Björkelund 2018) was similar to the overall meta‐analysis (Analysis 22.1).

The Knapstad 2020 study investigated the numbers of workers off work and found no difference between the improved care and the care as usual condition (RR 0.97, 95% CI 0.77 to 1.21; Analysis 14.2).

Data on the depressive symptoms were available for six studies (Björkelund 2018; Kendrick 2005; Knapstad 2020; Simon 1998; Wang 2007; Wikberg 2017). The pooled results of these studies showed that improved care management led to fewer depressive symptoms (SMD ‐0.21, 95% CI ‐0.35 to ‐0.07; Analysis 14.3).

One study (Wang 2007) also reported on work functioning. This study found more work functioning problems in the care management condition compared to care as usual (SMD 0.50, 95% CI 0.34 to 0.66; Analysis 14.4).

2.9 Improved care compared to care as usual (long‐term follow‐up)

One study (Schoenbaum 2001) reported the long‐term outcomes of improved care management. This study showed no difference in the number of workers who were at were off work (RR 1.06, 95% CI 0.90 to 1.23; Analysis 15.1). However workers receiving improved care had fewer depressive symptoms compared to workers receiving care as usual (RR 0.89, 95% CI 0.81 to 0.98; Analysis 15.2).

2.10 Exercise intervention compared to care as usual or relaxation (medium‐term follow‐up)

Three studies (Kaldo 2018; Krogh 2009; Krogh 2012) examined the effect of an exercise intervention, either compared with care as usual (Kaldo 2018) or compared with relaxation (Krogh 2009; Krogh 2012). The Krogh 2009 study had two study arms.

The Krogh 2009 and the Krogh 2012 both reported the sickness absence days, but the inconsistency (I²) in this meta‐analysis was 90.2%, we therefore refrained from pooling the results for this outcome. The results for days of sickness absence are therefore presented for the two subgroups separately.

2.10.1 Strength exercise versus relaxation

The Krogh 2009 found that supervised strength exercise led to fewer sickness absence days compared to relaxation (SMD ‐1.11; 95% CI ‐1.68 to ‐0.54), but no difference in depressive symptoms (SMD 0.15, 95% CI ‐0.39 to 0.68). See Analysis 16.1.

2.10.2 Aerobic exercise versus relaxation or stretching

The pooled effect of two studies (Krogh 2009; Krogh 2012) showed that aerobic exercise did not lead to fewer sickness absence days than relaxation or stretching in reducing sickness absence (SMD ‐0.06; 95% CI ‐0.36 to 0.24; Analysis 16.1).

Both studies also reported on depressive symptoms and also found no differences between the two conditions for this outcome (SMD ‐0.06, 95% CI ‐0.36 to 0.24).

The Kaldo 2018 study compared an exercise intervention with care as usual (primary care) and reported on the number of workers who were off work. No difference in being at work was found between the two conditions (RR 0.38, 95% CI 0.02 to 8.62; Analysis 16.2).

The Kaldo 2018 study also reported on work functioning and found no difference in work functioning problems between the two conditions (SMD 0.00, 95% CI ‐0.18 to 0.18; Analysis 16.4).

2.11 Art therapy compared to care as usual (medium‐term follow‐up)

One study (Blomdahl 2018) compared art therapy with care as usual. This study showed no difference in days of sickness absence between the two conditions (SMD ‐0.13, 95% CI ‐0.58 to 0.31; Analysis 17.1).

This study also reported on depressive symptoms, and found no difference in depressive symptoms between the two conditions (SMD ‐0.43, 95% CI ‐0.88 to 0.02; Analysis 17.2).

2.12 Diet compared to social support (medium‐term follow‐up)

One study (Chatterton 2018) compared a diet intervention with a social support intervention. This study showed no difference in sickness absence days between the two conditions (SMD ‐0.30, 95% CI ‐0.78 to 0.18; Analysis 18.1).

This study also reported on depressive symptoms, and found lower levels of depressive symptoms in workers who received the diet intervention (SMD ‐4.91, 95% CI ‐5.99 to ‐3.83; Analysis 18.2).

Discussion

Summary of main results

We included 45 studies, of which 40 RCTs and five cluster‐RCTs, in the review, evaluating a total of 17 work‐directed interventions and 32 clinical interventions. Within these broad categories, the type of intervention varied from one study to another, which limited the number of studies in each predefined comparison. We present 'Summary of findings' tables for the comparisons with more than two included studies. summary of findings Table 1 presents the GRADE assessment of the certainty of the evidence per comparison.

Work‐directed and a clinical intervention compared with care as usual

There is moderate‐certainty evidence that a combination of a work‐directed and a clinical intervention probably reduces the number of sickness absence days in the medium term to a small degree (4 to 12 months; SMD ‐0.25) more than care as usual but this does not lead to a greater number of people at work in the intervention group at the end of a one‐year follow‐up or beyond. The SMD of ‐0.25 translates back to 0.5 fewer sickness absence days in the past two weeks (CI ‐0.7 to ‐0.2 days) or to 25 fewer sickness absence days during one year (CI ‐37.5 to ‐11.8). See summary of findings Table 1; Table 2.

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Table 2. Work‐directed plus clinical compared to care as usual in depressed people, long‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Work‐directed plus clinical compared to care as usual in depressed people, long‐term follow‐up
Patient or population: Depressed persons Setting:Various: workplaces, outpatient and occupational healthcare Intervention: Work‐directed plus clinical Comparison: Care as usual
Outcomes	Risk with work‐directed intervention plus clinical intervention	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Days of sickness absence, long‐term follow‐up	SMD 0.19 lower (0.49 lower to 0.12 higher)	179 (2 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}	The SMD translates back to ‐0.3 days per 2 weeks (CI ‐0.9 to 0.2) and ‐18.7 days in 12 months (‐48.3 to 11.8).
Depressive symptoms, long‐term follow‐up	SMD 0.63 lower (1.02 lower to 0.24 lower)	117 (1 RCT)	⊕⊕⊝⊝ LOW ³
Work functioning, long‐term follow‐up	SMD 0.25 lower (0.63 lower to 0.14 higher)	117 (1 RCT)	⊕⊕⊝⊝ LOW ³
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

¹Both studies at high risk because of unblinded outcome assessment. Rated down one level due to high risk of bias.

²Pooled effect size includes small harms and appreciable benefits; sample size small; rated down one level due to imprecision.

³One study only, with small number of participants; downgraded two levels due to imprecision.

There was high‐certainty evidence that a combination of a work‐directed and a clinical intervention does not lead to fewer people being off work at the end of follow‐up at medium term follow‐up, while we found low‐certainty evidence that a combination of a work‐directed and a clinical intervention may reduce depressive outcomes (SMD ‐0.25) and low‐certainty evidence of no effect on work functioning outcomes. See summary of findings Table 1.

Work‐directed compared with care as usual

There is low‐certainty evidence, based on two studies, that a specific work‐directed intervention alone may increase the number of sickness absence days compared with work‐directed care as usual (SMD 0.39, 95% CI 0.04 to 0.74) within one year follow‐up. This SMD translates back to an increase of 0.7 sickness absence days in two weeks (CI 0.1 to 1.3 days) or an increase of 38 days in 12 months (CI 3.9 to 73 days). This review also found moderate‐certainty evidence based on four studies that there is probably no effect of work‐directed interventions on depressive symptoms within the first year of follow‐up (SMD ‐ 0.10, 95% ‐0.30 CI to 0.10; 4 studies, moderate‐certainty evidence) and beyond (SMD 0.18, 95% CI ‐0.13 to 0.49; 1 study, low‐certainty evidence) and low‐certainty evidence of no effect on work functioning outcomes (SMD ‐ 0.32 95% CI ‐ 0.90 to 0.26; 1 study) within the first year of follow up. There further is moderate‐certainty evidence the intervention does not lead to a lower or greater number of people at work in the intervention group at the end of a one‐year follow‐up (RR 0.93, 95% CI 0.77 to 1.11; 1 study, moderate‐certainty evidence) or beyond (RR 1.00, 95% CI 0.82 to 1.22; 2 studies, moderate‐certainty evidence). See summary of findings Table 2 and Table 3

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Table 3. Work‐directed compared to care as usual in depressed people, long‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Work‐directed compared to care as usual in depressed people, long‐term follow‐up
Patient or population: Depressed persons Setting: Workplace and occupational healthcare Intervention: Work‐directed Comparison: Care as usual (long‐term)
Outcomes	Risk with care as usual	Risk with work‐directed intervention	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Off work	606 per 1.000	606 per 1.000 (497 to 739)	RR 1.00 (0.82 to 1.22)	363 (2 RCTs)	⊕⊕⊕⊝ MODERATE ¹
Depressive symptoms	‐	SMD 0.18 higher (0.13 lower to 0.49 higher)	‐	160 (1 RCT)	⊕⊕⊝⊝ LOW ²
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; RR: Risk ratio; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

¹CI includes appreciable harm and benefit. Rated down one level due to imprecision.

²CI include appreciable harm and benefit; one study only; rated down two levels due to imprecision.

Psychological interventions compared with care as usual

One study in this review compared a psychological intervention to care as usual in the short‐term (Birney 2016) and found low‐certainty evidence that there may be no difference in number of sickness absence days. The SMD ‐0.05 of translates back to a reduction of 0.1 days per 2 weeks (CI ‐0.5 to 0.3 days) or a reduction of 4.9 days in 12 months (‐27.6 to 16.8 days). See Table 4.

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Table 4. Psychological intervention compared to care as usual in depressed people, short‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Psychological intervention compared to care as usual in depressed people (short‐term follow‐up)
Patient or population: Depressed persons Setting: Various: workplaces, primary care, insurance institute and academic hospital Intervention: Psychological intervention Comparison: Care as usual (short‐term)
Outcomes	Risk with psychological intervention	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Days of sickness absence; follow‐up short term	SMD 0.05 lower (0.28 lower to 0.17 higher)	300 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	The SMD translates back to ‐0.1 days per 2 weeks (CI ‐0.5 to 0.3) or ‐4.9 days in 12 months (‐27.6 to 16.8).
Depressive symptoms	No data available
Work functioning	No data available
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

¹One study with high risk of bias; rated down one level.

²One study only with 300 participants; rated down one level.

We found low‐certainty evidence, based on nine studies, that a psychological intervention either face‐to‐face, or an E‐mental health intervention with or without guidance from a care provider may reduce the number of sickness absence days compared with care as usual at medium term follow‐up (SMD ‐0.15, 95% CI ‐0.28 to ‐0.03). This SMD translates back to a reduction of 0.3 days per 2 weeks (CI ‐0.5 to ‐0.1) or a reduction of 14.7 days in 12 months (‐27.6 to ‐3.0).

All these studies, except for Mackenzie 2014, also reported on depressive symptoms, leading to low‐certainty evidence that psychological interventions may reduce depressive symptoms (SMD ‐0.30, 95% CI ‐0.45 to ‐0.15).

See summary of findings Table 3.

Improved care compared with care as usual

We found that care management did not lead to fewer sickness absence days in the medium term in seven studies. The SMD translates back to a reduction of 0.1 days per 2 weeks (CI ‐0.3 to 0.1) or a reduction of 5.9 days in 12 months (‐14.8 to 3.9). However, a sensitivity analysis revealed that the studies with a lower risk of bias (Simon 1998 and Wang 2007) probably lead to fewer sickness absence days in the care management condition (SMD ‐0.20, 95% CI ‐0.35 to ‐0.05; moderate‐certainty evidence). The SMD of this sensitivity analysis translates back to a reduction of 0.4 days per 2 weeks (CI ‐0.6 to ‐0.1) or a reduction of 19.7 days in 12 months (CI ‐34.5 to ‐4.9).

We found moderate‐certainty evidence based on seven studies that improved care management probably leads to fewer depressive symptoms in the medium term (SMD ‐0.21, 95% CI ‐0.35 to ‐0.07). summary of findings Table 4.

For the long term, we found moderate‐certainty evidence based on one study that care management probably does not reduce the number of sickness absence days, nor the depressive symptoms. See Table 5.

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Table 5. Improved care compared to care as usual in depressed people, long‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Improved care compared to care as usual in depressed people
Patient or population: Depressed persons Setting: Primary Care and community mental health Intervention: Improved care Comparison: Care as usual
Outcomes	Risk with care as usual	Risk with improved care	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Off work, long‐term follow‐up	607 per 1.000	656 per 1.000 (601 to 717)	RR 1.08 (0.99 to 1.18)	1356 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹
Depressed yes/no, long‐term follow‐up	614 per 1.000	546 per 1.000 (497 to 602)	RR 0.89 (0.81 to 0.98)	1356 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹
Work functioning	No data available
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

¹At risk of bias because of lack of allocation concealment. Rated down one level due to high risk of bias.

Antidepressant medication

With regard to antidepressant medication, this review found highly inconsistent results regarding the effect of SSRIs compared with other medications on sickness absence days(four studies). Compared with SNRI medication (three studies), one single study found that SSRI reduced sickness absence (Wade 2008), no difference in effect on sickness absence was found in another (Fernandez 2005), and a non‐significant difference in effect on sickness absence was found in the last (Romeo 2004). One single study found that a SSRI did not reduce sickness absence more than TCA medication (Miller 1998). One study (Fantino 2007) compared one SSRI with another SSRI. This study found that escitalopram reduced sickness absence more than citalopram (SMD ‐0.31). One study compared a TCA or MAO with placebo (Agosti 1991). This study found that the antidepressant medication did not reduce sickness absence more than placebo.

Overall completeness and applicability of evidence

The studies included in this review have been conducted in Europe, the United States of America, Australia and Canada only. Therefore, the generalisability of our findings to other parts of the world remains unclear. In line with our inclusion criteria, the included studies cover a range of clinical states. In 34 studies, a clinical diagnosis, most often a major depressive disorder according to the DSM‐IV or III, was used as an inclusion criterion, while in 11 studies included patients based on their symptom severity as measured by a questionnaire.

Moreover, study setting is likely to be a source of clinical heterogeneity. Studies were conducted in various settings, with most (28) taking place in primary care and outpatient settings. In five studies, patients were recruited in a workplace setting, and in another five in occupational health care. In many instances, the occupation of the participants was not reported even though it is conceivable that the effect of interventions partly depends on the specific work situation. A lack of studies on work‐related factors that may be predictors for work outcomes in depressed workers has already been pointed out (Lagerveld 2010). A meta‐analysis of prognostic studies did not identify work‐related prognostic factors for return to work in depressed workers (Ervasti 2017). A study by de Vries 2015 did find that work characteristics (work pace and workload, decision latitude, autonomy, relations with supervisor and job insecurity) were predictive of impaired work functioning after clinical recovery from a major depressive disorder. Moreover, studies have shown that work‐related factors are predictors of the clinical outcome for depression. For instance, Wang 2012 found long working hours to be associated with persistence of the depressive disorder over time. Therefore, we cannot assess the potential impact of work situations on the effectiveness of the included interventions.

In this updated review, we were able to include studies on work‐directed interventions as well as clinical interventions. While it is important to assess the effects of clinical interventions on occupational health, we are aware that the primary reason to choose between one or another clinical intervention is clinical effectiveness. However, in line with the emerging paradigm of value‐based medicine, it is central to care to offer interventions to patients providing the greatest patient value (Brown 2013). As being able to work may be one of the factors on which patient preference is based, so that assessing occupational health outcomes for clinical interventions is a key aspect. Moreover, from the point of view of patient preference, work functioning may be as important as sickness absence. However, in most included studies this outcome was not measured. Evaluating the effect of interventions on work functioning would further enable us to assess the patient value of these interventions.

In contrast to the first version of this review, we were able to include studies in most of the predefined comparisons. However, the number of studies within some of the comparison was small, and within some of the comparisons, the interventions were too dissimilar to pool the results. Another consequence of the low number of studies per comparison is that we were unable to perform subgroup analyses for participant and intervention characteristics and other sensitivity analyses which impedes the generalisation of the results.

The clinical relevance of the observed effects can best be evaluated by looking at the absolute differences in sickness absence days. It should, however, be noted that these differences vary from one study to another. Part of the explanation is that the outcome measure 'sickness absence days' is by definition partly determined by the length of follow up. The relevance of reductions in sickness absence days depends on the perspective of the stakeholder. A reduction in sickness absence of one day may not be relevant from the worker's point of view but can be relevant for stakeholders who bear the costs of the lost productivity, such as employers or insurance companies.

Quality of the evidence

Of the included studies, 40 were RCTs and five were cluster‐RCTs. The total number of participants in the analyses was 12,109. The number of participants in the smallest study subgroup was lower than 50 in 20 study arms, between 50 and 99 in 22 study arms, between 100 and 199 in 23 study arms, and 200 or more in 18. In some cases, the low number of participants was due to our need to focus only on a subgroup of the study population, disregarding participants with no or other mental disorders.

In the three cluster‐RCTs, allocation concealment was not adequate, probably indicative of the non‐feasibility of allocation concealment in this type of design due to all participants in one cluster (for example in a practice or with a healthcare provider) being automatically assigned to the same study arm. In seven further studies, information on random sequence generation or allocation concealment could not be retrieved, leading to a judgment of unclear risk of bias. In 35 studies, the allocation concealment was adequate and therefore posed a low risk of bias.

We found a high risk of performance bias in 10 included studies. In work‐directed interventions and in clinical interventions,such as psychological or exercise interventions, blinding of the participant or care provider is not feasible. However, the risk of performance bias also depends on how desirable the intervention is compared with the control group, according to either care providers or participants. One study evaluating a psychological intervention in addition to medication managed to compose two evenly desirable psychological interventions by ensuring an equal number of supportive, instead of therapeutic, sessions.

In this review, we chose to assess detection and attrition bias separately for sickness absence and depressive symptoms. We felt that not being blind to allocation may bias a self‐report assessment of depressive symptoms more than the reporting of a more factual outcome such as the days absent from work in a given period. In addition, sickness absence may be retrieved from employee attendance records while depression is measured with a self‐report questionnaire. In those instances, the lack of blinding of outcome assessment (detection bias) cannot influence the sickness absence but may well bias the depressive outcome. Nonetheless, the risk of detection bias for the outcome sickness absence was still high in 27 studies, which led to downgrading of the level of evidence in many comparisons.

Potential biases in the review process

This review included studies with a study population of both workers and non‐workers. This means that subgroups of the original sample were used for measuring the effect on sickness absence. These studies did not usually present all data for workers separately, but their sickness absence reports were by definition based on the workers in the study population. Some studies included participants with mental disorders other than depression. We included the studies in this review if the authors were willing to provide data for the depressed subgroup.

Subgroup analyses in individual studies may lead to biased results (Freemantle 2001), one reason being that testing many subgroups increases the likelihood of finding a statistically significant result by chance alone. We therefore predefined the subgroups and did not test multiple potential subgroups in the hope of finding a statistically significant finding. However, we acknowledge that a lack of power leading to statistically non‐significant findings may have occurred in our review. We, therefore, refrained from describing non‐significant findings with wide confidence intervals as evidence of no effect. In the future, we may have to reconsider our approach of selecting depressed workers only. The distinction between with depressive and other disorders, such as anxiety disorder may become less relevant as new insights are emerging based on the network perspective on psychopathology (Fried 2017). This approach involves investigating the importance and connections of individual symptoms rather than disorders. If future clinical treatments will use the most central symptom rather than a diagnostic category as a starting point for treatment, a review such as this may have to be organised around broader categories of psychological problems, such as common mental disorders, or around selected central depressive symptoms.

This review evaluates the effectiveness of a range of interventions aiming to reduce sickness absence in depressed workers rather than one specific intervention. While we believe this is appropriate for a complex and multifactorial outcome such as sickness absence, the categorisation of interventions under the comparisons has been challenging. This categorisation is likely to influence the results as it determines, for each intervention, with which other interventions the results will be pooled and to which other interventions it will be compared. The way interventions are categorised entails a potential bias in the review process. In the 2020 update, we have re‐organised the comparisons. One change was that we now distinguish between care as usual (a study arm where patients are treated without a specific intervention protocol) and an alternative intervention (an intervention that was protocolised, regardless of whether that intervention constitutes the regular care in that setting).

Another methodological issue concerns the handling of sickness absence data. For calculating standardized mean differences (SMDs) we considered sickness absence as a construct for which different instruments could be used, as long as they provided information on absenteeism. This meant that as long as we reported SMDs we could incorporate studies with different time spans (and therefore with a different maximum of sickness absence days during follow up) and scales that differed in the maximum score. Also, this enabled us to compare studies from various countries as we know that days of sickness absence tend to be calculated differently in different countries (for instance due to differences in whether calendar days or only work days are included as absenteeism days). Moreover, we transformed reports of days worked into days of sickness absence by extracting the days worked from the days that should have been worked ('the scale maximum'). This is analogous to transforming the scores of a scale in which a high score indicates a good outcome into a scale where a high score indicates a bad outcome. However, for this transformation we had to make inferences about the mean number of hours and the number of hours a day an employee would work in a specific country. This transformation, along with the different time spans, impedes the translation of standardized mean differences into overall mean of days of sickness absence.

Another issue regarding sickness absence data is that we accepted both self‐report and administrative databases as sources of data on sickness absence. Administrative databases are sometimes considered the gold standard. Agreement between the two sources has been reported to be good (Ferrie 2005; Severens 2000) but also limited (Pole 2006; van Poppel 2002). A meta‐analysis by Johns 2015 showed that in self‐report, workers tend to underestimate their days of sickness absence with a mean of two days. And a more recent study (Thorsen 2018) found that workers with fewer than 10 sickness absence days under‐reported and those with more than 30 days over‐reported the sickness absence days. As we included RCTs, the relative difference between the intervention was not affected by under‐ or overestimation in studies using self‐report. However, this does further complicate the translation of the effect estimates we found into days of sickness absence. In summary, caution is recommended when interpreting sickness absence data in meta‐analyses as this is as not all methodological issues have been thoroughly investigated.

Agreements and disagreements with other studies or reviews

Furlan 2012 searched the literature until 2010 and concluded that the evidence was of insufficient quality to determine which interventions are effective and are of value for the management of depression in the workplace. This conclusion was similar to the first published version of this review (Nieuwenhuijsen 2008). Our updated review has markedly different conclusions due to the inclusion of a substantially greater number of studies. In the current and the last update we were able to conclude that, at least with moderate certainty, work‐directed and clinical interventions combined are effective in reducing sickness absence. We also found low‐certainty evidence that psychological interventions are able to reduce sickness absence days better than care as usual.

Our finding that a work‐directed intervention alone does not reduce sickness absence is in line with the conclusion of a Cochrane systematic review (Vogel 2017) that return‐to‐work coordination programmes do not improve return‐to‐work outcomes in musculoskeletal and mental health problems. Our results further show that a combination of a work‐directed and a clinical intervention does have the potential to reduce sickness absence. One possible explanation for this is that the integration of the clinical and the work‐directed elements of an intervention is key in improving work outcomes.

Our finding that medication interventions show highly inconsistent effects on sickness absence has not changed with this new update. This is partly in line with findings of a systematic review (Lee 2018) which found that antidepressant medication had a positive effect on workplace functioning, but not on sickness absence. As we only included studies that measured our primary outcome, sickness absence, they included different studies in their review. Our review aims to completely cover the evidence for the effect on our primary outcome, and therefore our findings with regard to the secondary outcomes should be interpreted only in relation to the findings on our primary outcome.

Figure 1

PRISMA Study flow diagram of the study selection process until 2014.

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Figure 2

PRISMA Study flow diagram of the study selection process 2014‐2020.

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Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 4

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1: Work‐directed plus clinical versus CAU (medium‐term), Outcome 1: Days of sickness absence

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Analysis 1.2

Comparison 1: Work‐directed plus clinical versus CAU (medium‐term), Outcome 2: Off work

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Analysis 1.3

Comparison 1: Work‐directed plus clinical versus CAU (medium‐term), Outcome 3: Depressive symptoms

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Analysis 1.4

Comparison 1: Work‐directed plus clinical versus CAU (medium‐term), Outcome 4: Work functioning

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Analysis 2.1

Comparison 2: Work‐directed plus clinical versus CAU (long‐term), Outcome 1: Days of sickness absence

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Analysis 2.2

Comparison 2: Work‐directed plus clinical versus CAU (long‐term), Outcome 2: Depressive symptoms

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Analysis 2.3

Comparison 2: Work‐directed plus clinical versus CAU (long‐term), Outcome 3: Work functioning

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Analysis 3.1

Comparison 3: Work‐directed plus clinical versus psychological (medium‐term), Outcome 1: Days of sickness absence

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Analysis 3.2

Comparison 3: Work‐directed plus clinical versus psychological (medium‐term), Outcome 2: Depressive symptoms

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Analysis 3.3

Comparison 3: Work‐directed plus clinical versus psychological (medium‐term), Outcome 3: Work functioning

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Analysis 4.1

Comparison 4: Work‐directed plus clinical versus work‐directed (medium‐term), Outcome 1: Days of sickness absence

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Analysis 4.2

Comparison 4: Work‐directed plus clinical versus work‐directed (medium‐term), Outcome 2: Depressive symptoms

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Analysis 4.3

Comparison 4: Work‐directed plus clinical versus work‐directed (medium‐term), Outcome 3: Work functioning

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Analysis 5.1

Comparison 5: Work‐directed versus CAU (medium‐term), Outcome 1: Days of sickness absence

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Analysis 5.2

Comparison 5: Work‐directed versus CAU (medium‐term), Outcome 2: Off work

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Analysis 5.3

Comparison 5: Work‐directed versus CAU (medium‐term), Outcome 3: Depressive symptoms

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Analysis 5.4

Comparison 5: Work‐directed versus CAU (medium‐term), Outcome 4: Work functioning

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Analysis 6.1

Comparison 6: Work‐directed versus CAU (long‐term), Outcome 1: Off work

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Analysis 6.2

Comparison 6: Work‐directed versus CAU (long‐term), Outcome 2: Depressive symptoms

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Analysis 7.1

Comparison 7: Psychological intervention versus CAU (short‐term), Outcome 1: Days of sickness absence

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Analysis 8.1

Comparison 8: Psychological intervention versus CAU (medium‐term), Outcome 1: Days of sickness absence

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Analysis 8.2

Comparison 8: Psychological intervention versus CAU (medium‐term), Outcome 2: Depressive symptoms

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Analysis 8.3

Comparison 8: Psychological intervention versus CAU (medium‐term), Outcome 3: Work functioning

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Analysis 9.1

Comparison 9: Psychological intervention other psychological (medium‐term), Outcome 1: Days of sickness absence

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Analysis 9.2

Comparison 9: Psychological intervention other psychological (medium‐term), Outcome 2: Off work

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Analysis 9.3

Comparison 9: Psychological intervention other psychological (medium‐term), Outcome 3: Work functioning

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Analysis 9.4

Comparison 9: Psychological intervention other psychological (medium‐term), Outcome 4: Depressive symptoms

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Analysis 10.1

Comparison 10: Psychological intervention versus other psychological (long‐term), Outcome 1: Days of sickness absence

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Analysis 10.2

Comparison 10: Psychological intervention versus other psychological (long‐term), Outcome 2: Off work

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Analysis 10.3

Comparison 10: Psychological intervention versus other psychological (long‐term), Outcome 3: Depressive symptoms

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Analysis 10.4

Comparison 10: Psychological intervention versus other psychological (long‐term), Outcome 4: Work functioning

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Analysis 11.1

Comparison 11: Psychological with antidepressant versus antidepressant (medium‐term), Outcome 1: Days of sickness absence

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Analysis 11.2

Comparison 11: Psychological with antidepressant versus antidepressant (medium‐term), Outcome 2: Depressive symptoms

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Analysis 11.3

Comparison 11: Psychological with antidepressant versus antidepressant (medium‐term), Outcome 3: Work functioning

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Analysis 12.1

Comparison 12: Antidepressant medication versus placebo (medium‐term), Outcome 1: Days of sickness absence

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Analysis 12.2

Comparison 12: Antidepressant medication versus placebo (medium‐term), Outcome 2: Work functioning

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Analysis 13.1

Comparison 13: Antidepressant versus other antidepressant (medium‐term), Outcome 1: Days of sickness absence

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Analysis 13.2

Comparison 13: Antidepressant versus other antidepressant (medium‐term), Outcome 2: Depressive symptoms

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Analysis 13.3

Comparison 13: Antidepressant versus other antidepressant (medium‐term), Outcome 3: Work functioning

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Analysis 14.1

Comparison 14: Improved care versus CAU (medium‐term), Outcome 1: Days of Sickness absence

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Analysis 14.2

Comparison 14: Improved care versus CAU (medium‐term), Outcome 2: Off work

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Analysis 14.3

Comparison 14: Improved care versus CAU (medium‐term), Outcome 3: Depressive symptoms

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Analysis 14.4

Comparison 14: Improved care versus CAU (medium‐term), Outcome 4: Work functioning

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Analysis 15.1

Comparison 15: Improved care versus CAU (long‐term), Outcome 1: Off work

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Analysis 15.2

Comparison 15: Improved care versus CAU (long‐term), Outcome 2: Depressed yes/no

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Analysis 16.1

Comparison 16: Exercise intervention versus CAU or relaxation (medium‐term), Outcome 1: Days of sickness absence

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Analysis 16.2

Comparison 16: Exercise intervention versus CAU or relaxation (medium‐term), Outcome 2: Off work

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Analysis 16.3

Comparison 16: Exercise intervention versus CAU or relaxation (medium‐term), Outcome 3: Depressive symptoms

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Analysis 16.4

Comparison 16: Exercise intervention versus CAU or relaxation (medium‐term), Outcome 4: Work functioning

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Analysis 17.1

Comparison 17: Art therapy versus CAU (medium‐term), Outcome 1: Off work

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Analysis 17.2

Comparison 17: Art therapy versus CAU (medium‐term), Outcome 2: Depressive symptoms

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Analysis 18.1

Comparison 18: Adjunctive diet versus adjunctive social support (medium‐term), Outcome 1: Days of sickness absence

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Analysis 18.2

Comparison 18: Adjunctive diet versus adjunctive social support (medium‐term), Outcome 2: Depressive symptoms

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Analysis 19.1

Comparison 19: Sensitivity analysis: Work directed plus clinical versus CAU (medium‐term), Outcome 1: Days of sickness absence

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Analysis 20.1

Comparison 20: Sensitivity analysis: Psychotherapy versus CAU (medium‐term), Outcome 1: Days of sickness absence

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Analysis 21.1

Comparison 21: Sensitivity analysis: Improved care versus CAU, Outcome 1: Days of sickness absence

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Analysis 22.1

Comparison 22: Sensitivity analysis: Improved care versus CAU cluster, Outcome 1: Days of Sickness absence

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Summary of findings 1. Work‐directed plus clinical intervention compared to care as usual in depressed people, medium‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Work‐directed plus clinical intervention compared to care as usual (medium‐term) in depressed people
Patients: Depressed persons Setting: Various: workplaces, outpatient and occupational healthcare Intervention: Work‐directed plus clinical Control: Care as usual (medium‐term)
Outcomes	Risk with care as usual	Risk with work‐directed intervention plus clinical intervention	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sickness absence days	‐	SMD 0.25 SD lower (0.38 lower to 0.12 lower)	‐	1292 (9 RCTs)	⊕⊕⊕⊝ MODERATE ¹	The SMD translates back to ‐0.5 days per 2 weeks (CI ‐0.7 to ‐0.2) or ‐24.7 days in 12 months (‐37.5 to ‐11.8).
On sick leave	417 per 1.000	451 per 1.000 (267 to 764)	RR 1.08 (0.64 to 1.83)	1025 (2 RCTs)	⊕⊕⊕⊕ HIGH
Depressive symptoms‐	‐	SMD 0.25 SD lower (0.49 lower to 0.01 lower)	‐	1091 (8 RCTs)	⊕⊕⊝⊝ LOW ^{2 3}
Work functioning	‐	SMD 0.19 SD lower (0.43 lower to 0.06 higher)	‐	926 (5 RCTs)	⊕⊕⊝⊝ LOW ^{1 4 5}
The risk in the intervention group (and the 95% CI) is based on the risk in the control group and the relative effect of the intervention (and the 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; RR: Risk ratio; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹A majority of the studies in the meta‐analysis (in terms of weights) showed high or unclear risk on the randomisation items (sequence and concealment), blinded outcome assessment or attrition. We therefore rated down one level due to a high risk of bias. ²Depression is self‐reported and participants were not blinded. We rated down one level due to a high risk of bias. ³Study effects varied with some clearly indicating beneficial results and some not. We rated down one level due to imprecision. ⁴Rated down one level due to inconsistency (I² 61%). ⁵Pooled effect size includes small harmful effec. Rated down one level due to wide CI (imprecision)

Summary of findings 1. Work‐directed plus clinical intervention compared to care as usual in depressed people, medium‐term follow‐up

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Summary of findings 2. Work‐directed intervention compared to care as usual in depressed people, medium‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Work‐directed intervention compared to care as usual in depressed people
Patient or population: Depressed persons Setting: Workplace and occupational healthcare Intervention: Work‐directed Comparison: Care as usual (medium‐term)
Outcomes	Risk with care as usual	Risk with work‐directed intervention	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sickness absence days, medium‐term follow‐up	‐	SMD 0.39 higher (0.04 higher to 0.74 higher)	‐	130 (2 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}	The SMD translates back to + 0.7 days in two weeks (95% CI 0.1 to 1.3) or + 38 days in 12 months (95% CI 3.9 to 73).
Off work, medium‐term follow‐up	708 per 1.000	658 per 1.000 (545 to 786)	RR 0.93 (0.77 to 1.11)	226 (1 RCT)	⊕⊕⊕⊝ MODERATE ³
Depressive symptoms, medium‐term follow‐up	‐	SMD 0.1 lower (0.3 lower to 0.1 higher)	‐	390 (4 RCTs)	⊕⊕⊕⊝ MODERATE ⁴
Work functioning, medium‐term follow‐up	‐	SMD 0.32 lower (0.9 lower to 0.26 higher)	‐	48 (1 RCT)	⊕⊕⊝⊝ LOW ^{3 5}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; RR: Risk ratio; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹One study with unclear risk and one with serious risk of bias. Rated down one level due to high risk of bias. ²Two studies with 130 participants. CI includes harms and benefits. Rated down one level due to imprecision. ³Based on one study with small number of participants, rated down one level due to to imprecision. ⁴Includes studies with high risk of bias. Rated down one level due to high risk of bias. ⁵One study with unclear risk of bias. Rated down with one level due to high risk of bias.

Summary of findings 2. Work‐directed intervention compared to care as usual in depressed people, medium‐term follow‐up

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Summary of findings 3. Psychological intervention compared to care as usual in depressed people, medium‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Psychological intervention compared to care as usual in depressed people
Patient or population: Depressed persons Setting: Various: workplaces, primary care, insurance institute and academic hospital Intervention: Psychological intervention Comparison: Care as usual
Outcomes	Risk with psychological intervention	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sickness absence days, medium‐term follow‐up	SMD 0.15 lower (0.28 lower to 0.03 lower)	1649 (9 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}	The SMD translates back to ‐0.3 days per 2 weeks (95% CI ‐0.5 to ‐0.1) or ‐14.7 days in 12 months (95% CI ‐27.6 to ‐3.0).
Depressive symptoms, medium‐term follow‐up	SMD 0.3 lower (0.45 lower to 0.15 lower)	1255 (8 RCTs)	⊕⊕⊝⊝ LOW ^{2 3}
Work ability, medium‐term follow‐up	SMD 0.05 higher (0.46 lower to 0.57 higher)	58 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{4 5}
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹In most studies, the outcome was self‐reported, leading to risk of bias in outcome assessment. There was also large attrition. Rated down one level due to high risk of bias. ²Funnel plot shows missing small studies with no effect or harmful effect. Rated down one level due to risk of publication bias. ³Outcomes self‐reported in unblinded studies. Rated down one level due to high risk of bias ⁴CI includes appreciable harms and benefits. Sole study. Rated down two levels due to imprecision. ⁵One study with unclear risk of bias. Rated down one level due to high risk of bias.

Summary of findings 3. Psychological intervention compared to care as usual in depressed people, medium‐term follow‐up

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Summary of findings 4. Improved care compared to care as usual in depressed people, medium‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Improved care compared to care as usual in depressed persons
Patient or population: Depressed persons Setting: Primary Care and community mental health Intervention: Improved Care Comparison: Care as usual
Outcomes	Risk with care as usual	Risk with improved care	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Sickness absence days, medium‐term follow‐up	‐	SMD 0.06 lower (0.15 lower to 0.04 higher)¹	‐	1912 (7 RCTs)	⊕⊕⊕⊝ MODERATE ²	The SMD translates back to ‐0.1 days per 2 weeks (95% CI ‐0.3 to 0.1) or ‐5.9 days in 12 months (95% CI ‐14.8 to 3.9). The SMD of the sensitivity analysis¹ translates back to ‐0.4 days per 2 weeks (95% CI ‐0.6 to ‐0.1) or ‐19.7 days in 12 months (95% CI ‐34.5 to ‐4.9).
Off work, medium‐term follow up	496 per 1.000	516 per 1.000 (402 to 655)	RR 0.97 (0.77 to 1.22)	362 (1 RCT)	⊕⊕⊝⊝ LOW ^3,4
Depressive symptoms, medium‐term follow‐up	‐	SMD 0.21 SD lower (0.35 lower to 0.07 lower)	‐	1808 (7 RCTs)	⊕⊕⊕⊝ MODERATE ²
Work functioning, medium‐term follow‐up	‐	SMD 0.5 higher (0.34 higher to 0.66 higher)	‐	604 (1 RCT)	⊕⊕⊕⊝ MODERATE ⁵
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; RR: Risk ratio; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
1 A sensitivity analysis revealed that two RCTs with a lower risk of bias found a SMD of 0.20 lower (0.35 lower to 0.05 lower); moderate‐certainty evidence). 2 Majority of studies at high risk; downgraded with one level due to high risk of bias. 3 One study at high risk of bias, downgraded with one level due to high risk of bias. 4 One study with less than 400 participants, downgraded with one level due to imprecision 5 Study with unblinded outcome assessment, rated down one level due to high risk of bias.

Summary of findings 4. Improved care compared to care as usual in depressed people, medium‐term follow‐up

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Table 1. Work functioning outcome: Risk of bias

Study	Blinding of outcome assessment (detection bias)	Incomplete outcome data: attrition bias
Agosti 1991	Low risk (blinded clinician)	High risk
Burnand 2002	High risk (self‐report)	High risk
Finnes 2017	High risk (self‐report)	Low risk
Hees 2013	High risk (self‐report)	Low risk
Kaldo 2018	High risk (self‐report)	High risk
Knekt 2013	High risk (self‐report)	Low risk
Lerner 2012	High risk (self‐report)	Low risk
Miller 1998	High risk (self‐report)	Unclear risk
Sarfati 2016	High risk (self‐report)	High risk
Wang 2007	High risk (self‐report)	Low risk
Lerner 2020	High risk (self‐report)	Low risk

Table 1. Work functioning outcome: Risk of bias

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Table 2. Work‐directed plus clinical compared to care as usual in depressed people, long‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Work‐directed plus clinical compared to care as usual in depressed people, long‐term follow‐up
Patient or population: Depressed persons Setting:Various: workplaces, outpatient and occupational healthcare Intervention: Work‐directed plus clinical Comparison: Care as usual
Outcomes	Risk with work‐directed intervention plus clinical intervention	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Days of sickness absence, long‐term follow‐up	SMD 0.19 lower (0.49 lower to 0.12 higher)	179 (2 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}	The SMD translates back to ‐0.3 days per 2 weeks (CI ‐0.9 to 0.2) and ‐18.7 days in 12 months (‐48.3 to 11.8).
Depressive symptoms, long‐term follow‐up	SMD 0.63 lower (1.02 lower to 0.24 lower)	117 (1 RCT)	⊕⊕⊝⊝ LOW ³
Work functioning, long‐term follow‐up	SMD 0.25 lower (0.63 lower to 0.14 higher)	117 (1 RCT)	⊕⊕⊝⊝ LOW ³
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹Both studies at high risk because of unblinded outcome assessment. Rated down one level due to high risk of bias. ²Pooled effect size includes small harms and appreciable benefits; sample size small; rated down one level due to imprecision. ³One study only, with small number of participants; downgraded two levels due to imprecision.

Table 2. Work‐directed plus clinical compared to care as usual in depressed people, long‐term follow‐up

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Table 3. Work‐directed compared to care as usual in depressed people, long‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Work‐directed compared to care as usual in depressed people, long‐term follow‐up
Patient or population: Depressed persons Setting: Workplace and occupational healthcare Intervention: Work‐directed Comparison: Care as usual (long‐term)
Outcomes	Risk with care as usual	Risk with work‐directed intervention	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Off work	606 per 1.000	606 per 1.000 (497 to 739)	RR 1.00 (0.82 to 1.22)	363 (2 RCTs)	⊕⊕⊕⊝ MODERATE ¹
Depressive symptoms	‐	SMD 0.18 higher (0.13 lower to 0.49 higher)	‐	160 (1 RCT)	⊕⊕⊝⊝ LOW ²
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; RR: Risk ratio; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹CI includes appreciable harm and benefit. Rated down one level due to imprecision. ²CI include appreciable harm and benefit; one study only; rated down two levels due to imprecision.

Table 3. Work‐directed compared to care as usual in depressed people, long‐term follow‐up

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Table 4. Psychological intervention compared to care as usual in depressed people, short‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Psychological intervention compared to care as usual in depressed people (short‐term follow‐up)
Patient or population: Depressed persons Setting: Various: workplaces, primary care, insurance institute and academic hospital Intervention: Psychological intervention Comparison: Care as usual (short‐term)
Outcomes	Risk with psychological intervention	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Days of sickness absence; follow‐up short term	SMD 0.05 lower (0.28 lower to 0.17 higher)	300 (1 RCT)	⊕⊕⊝⊝ LOW ^{1 2}	The SMD translates back to ‐0.1 days per 2 weeks (CI ‐0.5 to 0.3) or ‐4.9 days in 12 months (‐27.6 to 16.8).
Depressive symptoms	No data available
Work functioning	No data available
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; SMD: Standardised mean difference.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹One study with high risk of bias; rated down one level. ²One study only with 300 participants; rated down one level.

Table 4. Psychological intervention compared to care as usual in depressed people, short‐term follow‐up

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Table 5. Improved care compared to care as usual in depressed people, long‐term follow‐up

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Improved care compared to care as usual in depressed people
Patient or population: Depressed persons Setting: Primary Care and community mental health Intervention: Improved care Comparison: Care as usual
Outcomes	Risk with care as usual	Risk with improved care	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Off work, long‐term follow‐up	607 per 1.000	656 per 1.000 (601 to 717)	RR 1.08 (0.99 to 1.18)	1356 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹
Depressed yes/no, long‐term follow‐up	614 per 1.000	546 per 1.000 (497 to 602)	RR 0.89 (0.81 to 0.98)	1356 (1 RCT)	⊕⊕⊕⊝ MODERATE ¹
Work functioning	No data available
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RCT: Randomised controlled trial; RR: Risk ratio.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹At risk of bias because of lack of allocation concealment. Rated down one level due to high risk of bias.

Table 5. Improved care compared to care as usual in depressed people, long‐term follow‐up

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Comparison 1. Work‐directed plus clinical versus CAU (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Days of sickness absence Show forest plot	9	1292	Std. Mean Difference (IV, Random, 95% CI)	‐0.25 [‐0.38, ‐0.12]

1.1.1 Work‐directed plus clinical vs. CAU‐psych	2	179	Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.61, 0.01]
1.1.2 Work‐directed plus clinical vs. CAU‐PC	4	718	Std. Mean Difference (IV, Random, 95% CI)	‐0.32 [‐0.56, ‐0.07]
1.1.3 Work‐directed plus clinical vs CAU‐WD	2	270	Std. Mean Difference (IV, Random, 95% CI)	‐0.20 [‐0.44, 0.04]
1.1.4 Work‐directed plus clinical vs CAU‐no int	1	125	Std. Mean Difference (IV, Random, 95% CI)	0.02 [‐0.33, 0.37]
1.2 Off work Show forest plot	2	1025	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.64, 1.83]

1.2.1 Work‐directed plus clinical vs. CAU‐PC	1	392	Risk Ratio (M‐H, Random, 95% CI)	1.73 [0.70, 4.24]
1.2.2 Work‐directed plus clinical vs CAU‐WD	1	633	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.83, 1.06]
1.3 Depressive symptoms Show forest plot	8	1091	Std. Mean Difference (IV, Random, 95% CI)	‐0.25 [‐0.49, ‐0.01]

1.3.1 work‐directed plus clinical vs. CAU‐psych	2	179	Std. Mean Difference (IV, Random, 95% CI)	‐0.08 [‐0.66, 0.50]
1.3.2 Work‐directed plus clinical vs. CAU‐PC	4	713	Std. Mean Difference (IV, Random, 95% CI)	‐0.44 [‐0.73, ‐0.15]
1.3.3 Work‐directed plus clinical vs. CAU‐WD	1	74	Std. Mean Difference (IV, Random, 95% CI)	0.26 [‐0.20, 0.72]
1.3.4 Work‐directed plus clinical vs. CAU‐no int	1	125	Std. Mean Difference (IV, Random, 95% CI)	‐0.23 [‐0.59, 0.12]
1.4 Work functioning Show forest plot	5	926	Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.43, 0.06]

1.4.1 Work‐directed plus clinical vs. CAU‐psych	1	117	Std. Mean Difference (IV, Random, 95% CI)	‐0.09 [‐0.48, 0.29]
1.4.2 work‐directed plus clinical vs. CAU‐GP	4	809	Std. Mean Difference (IV, Random, 95% CI)	‐0.22 [‐0.53, 0.09]

Comparison 1. Work‐directed plus clinical versus CAU (medium‐term)

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Comparison 2. Work‐directed plus clinical versus CAU (long‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Days of sickness absence Show forest plot	2	179	Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.49, 0.12]

2.1.1 Work‐directed plus clinical vs. CAU‐psych	2	179	Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.49, 0.12]
2.2 Depressive symptoms Show forest plot	1	117	Std. Mean Difference (IV, Random, 95% CI)	‐0.63 [‐1.02, ‐0.24]

2.2.1 Work‐directed plus clinical vs. CAU‐psych	1	117	Std. Mean Difference (IV, Random, 95% CI)	‐0.63 [‐1.02, ‐0.24]
2.3 Work functioning Show forest plot	1	117	Std. Mean Difference (IV, Random, 95% CI)	‐0.25 [‐0.63, 0.14]

2.3.1 Work‐directed plus clinical vs. CAU	1	117	Std. Mean Difference (IV, Random, 95% CI)	‐0.25 [‐0.63, 0.14]

Comparison 2. Work‐directed plus clinical versus CAU (long‐term)

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Comparison 3. Work‐directed plus clinical versus psychological (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Days of sickness absence Show forest plot	1	59	Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.47, 0.56]

3.2 Depressive symptoms Show forest plot	1	53	Std. Mean Difference (IV, Random, 95% CI)	‐0.15 [‐0.69, 0.39]

3.3 Work functioning Show forest plot	1	51	Std. Mean Difference (IV, Random, 95% CI)	‐0.08 [‐0.63, 0.48]

Comparison 3. Work‐directed plus clinical versus psychological (medium‐term)

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Comparison 4. Work‐directed plus clinical versus work‐directed (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Days of sickness absence Show forest plot	1	51	Std. Mean Difference (IV, Random, 95% CI)	‐0.10 [‐0.65, 0.45]

4.2 Depressive symptoms Show forest plot	1	43	Std. Mean Difference (IV, Random, 95% CI)	‐0.37 [‐0.98, 0.23]

4.3 Work functioning Show forest plot	1	41	Std. Mean Difference (IV, Random, 95% CI)	0.32 [‐0.30, 0.94]

Comparison 4. Work‐directed plus clinical versus work‐directed (medium‐term)

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Comparison 5. Work‐directed versus CAU (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Days of sickness absence Show forest plot	2	130	Std. Mean Difference (IV, Random, 95% CI)	0.39 [0.04, 0.74]

5.1.1 Work‐directed vs. CAU‐PC	1	55	Std. Mean Difference (IV, Random, 95% CI)	0.30 [‐0.24, 0.83]
5.1.2 Work‐directed vs. CAU‐WD	1	75	Std. Mean Difference (IV, Random, 95% CI)	0.45 [‐0.00, 0.91]
5.2 Off work Show forest plot	1	226	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.77, 1.11]

5.2.1 Work‐directed vs CAU‐WD	1	226	Risk Ratio (M‐H, Fixed, 95% CI)	0.92 [0.77, 1.11]
5.3 Depressive symptoms Show forest plot	4	390	Std. Mean Difference (IV, Random, 95% CI)	‐0.10 [‐0.30, 0.10]

5.3.1 Work‐directed vs. CAU‐PC	1	48	Std. Mean Difference (IV, Random, 95% CI)	0.23 [‐0.35, 0.81]
5.3.2 Work‐directed vs. CAU‐WD	3	342	Std. Mean Difference (IV, Random, 95% CI)	‐0.14 [‐0.36, 0.07]
5.4 Work functioning Show forest plot	1	48	Std. Mean Difference (IV, Random, 95% CI)	‐0.32 [‐0.90, 0.26]

5.4.1 Work‐directed vs. CAU‐PC	1	48	Std. Mean Difference (IV, Random, 95% CI)	‐0.32 [‐0.90, 0.26]

Comparison 5. Work‐directed versus CAU (medium‐term)

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Comparison 6. Work‐directed versus CAU (long‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Off work Show forest plot	2	363	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.82, 1.22]

6.1.1 Work‐directed vs CAU‐WD	2	363	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.82, 1.22]
6.2 Depressive symptoms Show forest plot	1	160	Std. Mean Difference (IV, Random, 95% CI)	0.18 [‐0.13, 0.49]

6.2.1 Work‐directed vs. CAU‐WD	1	160	Std. Mean Difference (IV, Random, 95% CI)	0.18 [‐0.13, 0.49]

Comparison 6. Work‐directed versus CAU (long‐term)

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Comparison 7. Psychological intervention versus CAU (short‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
7.1 Days of sickness absence Show forest plot	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

7.1.1 I‐Unguided	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

Comparison 7. Psychological intervention versus CAU (short‐term)

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Comparison 8. Psychological intervention versus CAU (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
8.1 Days of sickness absence Show forest plot	9	1649	Std. Mean Difference (IV, Random, 95% CI)	‐0.15 [‐0.28, ‐0.03]

8.1.1 Face‐to‐face	1	63	Std. Mean Difference (IV, Random, 95% CI)	0.15 [‐0.34, 0.65]
8.1.2 T‐guided	1	12	Std. Mean Difference (IV, Random, 95% CI)	‐0.34 [‐1.50, 0.82]
8.1.3 I‐guided	5	639	Std. Mean Difference (IV, Random, 95% CI)	‐0.15 [‐0.36, 0.05]
8.1.4 I‐Unguided	2	935	Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.41, 0.03]
8.2 Depressive symptoms Show forest plot	8	1255	Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.45, ‐0.15]

8.2.1 Face to face	1	58	Std. Mean Difference (IV, Random, 95% CI)	0.02 [‐0.49, 0.54]
8.2.2 T‐guided	1	12	Std. Mean Difference (IV, Random, 95% CI)	‐0.76 [‐1.97, 0.45]
8.2.3 I‐guided	4	666	Std. Mean Difference (IV, Random, 95% CI)	‐0.44 [‐0.60, ‐0.27]
8.2.4 Unguided	2	519	Std. Mean Difference (IV, Random, 95% CI)	‐0.14 [‐0.31, 0.03]
8.3 Work functioning Show forest plot	1	58	Std. Mean Difference (IV, Random, 95% CI)	0.05 [‐0.46, 0.57]

8.3.1 Face to face	1	58	Std. Mean Difference (IV, Random, 95% CI)	0.05 [‐0.46, 0.57]

Comparison 8. Psychological intervention versus CAU (medium‐term)

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Comparison 9. Psychological intervention other psychological (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
9.1 Days of sickness absence Show forest plot	1	98	Std. Mean Difference (IV, Random, 95% CI)	0.70 [‐0.19, 1.59]

9.1.1 Short‐term psychodynamic therapy vs. solution‐focused therapy	1	47	Std. Mean Difference (IV, Random, 95% CI)	0.25 [‐0.39, 0.89]
9.1.2 Long‐term psychodynamic therapy vs. solution‐focused therapy	1	51	Std. Mean Difference (IV, Random, 95% CI)	1.16 [0.49, 1.83]
9.2 Off work Show forest plot	1	218	Risk Ratio (IV, Random, 95% CI)	1.83 [1.00, 3.37]

9.2.1 Short‐term psychotherapy vs. coping focussed therapy	1	218	Risk Ratio (IV, Random, 95% CI)	1.83 [1.00, 3.37]
9.3 Work functioning Show forest plot	1		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

9.3.1 Short‐term psychodynamic therapy vs solution‐focused therapy	1	136	Std. Mean Difference (IV, Random, 95% CI)	‐0.66 [‐1.03, ‐0.30]
9.3.2 Long‐term psychodynamic therapy vs solution‐focused therapy	1	160	Std. Mean Difference (IV, Random, 95% CI)	1.00 [0.63, 1.36]
9.4 Depressive symptoms Show forest plot	1		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

9.4.1 Short‐term psychodynamic therapy vs. solution‐focused therapy	1	136	Std. Mean Difference (IV, Random, 95% CI)	‐1.19 [‐1.58, ‐0.81]
9.4.2 Long‐term psychodynamic therapy vs. solution‐focused therapy	1	160	Std. Mean Difference (IV, Random, 95% CI)	2.04 [1.62, 2.45]

Comparison 9. Psychological intervention other psychological (medium‐term)

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Comparison 10. Psychological intervention versus other psychological (long‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
10.1 Days of sickness absence Show forest plot	1		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

10.1.1 Short‐term psychodynamic therapy vs. solution‐focused therapy	1	36	Std. Mean Difference (IV, Random, 95% CI)	‐0.91 [‐1.62, ‐0.19]
10.1.2 Long‐term psychodynamic therapy vs. solution‐focused therapy	1	42	Std. Mean Difference (IV, Random, 95% CI)	‐4.61 [‐5.84, ‐3.39]
10.2 Off work Show forest plot	1	216	Risk Ratio (IV, Fixed, 95% CI)	1.14 [0.61, 2.11]

10.2.1 Short‐term psychotherapy vs. coping focussed therapy	1	216	Risk Ratio (IV, Fixed, 95% CI)	1.14 [0.61, 2.11]
10.3 Depressive symptoms Show forest plot	2		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

10.3.1 Short‐term psychodynamic therapy vs. solution‐focused therapy	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected
10.3.2 Long‐term psychodynamic therapy vs. solution‐focused therapy	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected
10.3.3 Short term solution focused vs brief psychotherapy fu > 1 year	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected
10.4 Work functioning Show forest plot	1	263	Std. Mean Difference (IV, Random, 95% CI)	‐0.26 [‐0.52, 0.01]

10.4.1 Short‐term psychodynamic therapy vs. solution‐focused therapy	1	118	Std. Mean Difference (IV, Random, 95% CI)	‐0.33 [‐0.72, 0.05]
10.4.2 Long‐term psychodynamic therapy vs. solution‐focused therapy	1	145	Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.56, 0.18]

Comparison 10. Psychological intervention versus other psychological (long‐term)

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Comparison 11. Psychological with antidepressant versus antidepressant (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
11.1 Days of sickness absence Show forest plot	2	139	Std. Mean Difference (IV, Random, 95% CI)	‐0.38 [‐0.99, 0.24]

11.1.1 Psychodynamic therapy plus TCA vs. TCA	1	57	Std. Mean Difference (IV, Random, 95% CI)	‐0.71 [‐1.25, ‐0.17]
11.1.2 I‐CBT plus AD vs AD plus reminder	1	82	Std. Mean Difference (IV, Random, 95% CI)	‐0.08 [‐0.52, 0.35]
11.2 Depressive symptoms Show forest plot	2	160	Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.50, 0.12]

11.2.1 Psychodynamic therapy plus TCA vs TCS	1	74	Std. Mean Difference (IV, Random, 95% CI)	‐0.11 [‐0.57, 0.35]
11.2.2 I‐CBT plus AD vs AD plus reminder	1	86	Std. Mean Difference (IV, Random, 95% CI)	‐0.26 [‐0.69, 0.16]
11.3 Work functioning Show forest plot	2	141	Std. Mean Difference (IV, Random, 95% CI)	‐0.24 [‐0.68, 0.20]

11.3.1 Psychodynamic therapy plus TCA vs. TCA	1	57	Std. Mean Difference (IV, Random, 95% CI)	‐0.49 [‐1.02, 0.04]
11.3.2 I‐CBT plus AD vs AD plus reminder	1	84	Std. Mean Difference (IV, Random, 95% CI)	‐0.04 [‐0.47, 0.39]

Comparison 11. Psychological with antidepressant versus antidepressant (medium‐term)

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Comparison 12. Antidepressant medication versus placebo (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
12.1 Days of sickness absence Show forest plot	1	61	Std. Mean Difference (IV, Random, 95% CI)	0.48 [‐0.05, 1.00]

12.1.1 TCA or MAO vs. placebo	1	61	Std. Mean Difference (IV, Random, 95% CI)	0.48 [‐0.05, 1.00]
12.2 Work functioning Show forest plot	1	61	Std. Mean Difference (IV, Random, 95% CI)	‐0.58 [‐1.11, ‐0.05]

12.2.1 TCA or MAO vs. placebo	1	61	Std. Mean Difference (IV, Random, 95% CI)	‐0.58 [‐1.11, ‐0.05]

Comparison 12. Antidepressant medication versus placebo (medium‐term)

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Comparison 13. Antidepressant versus other antidepressant (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
13.1 Days of sickness absence Show forest plot	5		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

13.1.1 SSRI vs. SNRI	3		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected
13.1.2 SSRI vs. TCA	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected
13.1.3 SSRI vs. SSRI	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected
13.2 Depressive symptoms Show forest plot	5	1514	Std. Mean Difference (IV, Random, 95% CI)	0.07 [‐0.34, 0.48]

13.2.1 SSRI vs. SNRI	3	599	Std. Mean Difference (IV, Random, 95% CI)	0.18 [‐0.37, 0.73]
13.2.2 SSRI vs. TCA	1	635	Std. Mean Difference (IV, Random, 95% CI)	Not estimable
13.2.3 SSRI vs. SSRI	1	280	Std. Mean Difference (IV, Random, 95% CI)	‐0.23 [‐0.47, 0.00]
13.3 Work functioning Show forest plot	1	635	Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.16, 0.06]

13.3.1 SSRI vs. TCA	1	635	Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.16, 0.06]

Comparison 13. Antidepressant versus other antidepressant (medium‐term)

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Comparison 14. Improved care versus CAU (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
14.1 Days of Sickness absence Show forest plot	6	1912	Std. Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.16, 0.06]

14.2 Off work Show forest plot	1	362	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.77, 1.21]

14.3 Depressive symptoms Show forest plot	6	1808	Std. Mean Difference (IV, Random, 95% CI)	‐0.21 [‐0.35, ‐0.07]

14.4 Work functioning Show forest plot	1	604	Std. Mean Difference (IV, Random, 95% CI)	0.50 [0.34, 0.66]

Comparison 14. Improved care versus CAU (medium‐term)

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Comparison 15. Improved care versus CAU (long‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
15.1 Off work Show forest plot	1	1356	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.90, 1.23]

15.2 Depressed yes/no Show forest plot	1	1356	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.81, 0.98]

Comparison 15. Improved care versus CAU (long‐term)

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Comparison 16. Exercise intervention versus CAU or relaxation (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
16.1 Days of sickness absence Show forest plot	2		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

16.1.1 Supervised strength training vs. relaxation	1	65	Std. Mean Difference (IV, Random, 95% CI)	‐1.11 [‐1.68, ‐0.54]
16.1.2 Aerobic exercise vs. relaxation/stretching	2	180	Std. Mean Difference (IV, Random, 95% CI)	‐0.06 [‐0.36, 0.24]
16.2 Off work Show forest plot	1	28	Risk Ratio (M‐H, Random, 95% CI)	0.38 [0.02, 8.62]

16.2.1 Aerobic exercise versus CAU‐PC	1	28	Risk Ratio (M‐H, Random, 95% CI)	0.38 [0.02, 8.62]
16.3 Depressive symptoms Show forest plot	2		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only

16.3.1 Supervised strength training vs. relaxation	1	65	Std. Mean Difference (IV, Random, 95% CI)	0.15 [‐0.39, 0.68]
16.3.2 Aerobic exercise vs. relaxation/stretching	2	180	Std. Mean Difference (IV, Random, 95% CI)	0.18 [‐0.12, 0.48]
16.4 Work functioning Show forest plot	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

16.4.1 Aerobic exercise vs CAU‐GP	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

Comparison 16. Exercise intervention versus CAU or relaxation (medium‐term)

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Comparison 17. Art therapy versus CAU (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
17.1 Off work Show forest plot	1	79	Std. Mean Difference (IV, Random, 95% CI)	‐0.13 [‐0.58, 0.31]

17.2 Depressive symptoms Show forest plot	1	79	Std. Mean Difference (IV, Fixed, 95% CI)	‐0.43 [‐0.88, 0.02]

Comparison 17. Art therapy versus CAU (medium‐term)

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Comparison 18. Adjunctive diet versus adjunctive social support (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
18.1 Days of sickness absence Show forest plot	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

18.2 Depressive symptoms Show forest plot	1	56	Std. Mean Difference (IV, Fixed, 95% CI)	‐4.91 [‐5.99, ‐3.83]

Comparison 18. Adjunctive diet versus adjunctive social support (medium‐term)

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Comparison 19. Sensitivity analysis: Work directed plus clinical versus CAU (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
19.1 Days of sickness absence Show forest plot	9	1292	Std. Mean Difference (IV, Random, 95% CI)	‐0.25 [‐0.38, ‐0.12]

19.1.1 Low risk of bias	8	912	Std. Mean Difference (IV, Random, 95% CI)	‐0.24 [‐0.41, ‐0.08]
19.1.2 High risk of bias	1	380	Std. Mean Difference (IV, Random, 95% CI)	‐0.28 [‐0.48, ‐0.08]

Comparison 19. Sensitivity analysis: Work directed plus clinical versus CAU (medium‐term)

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Comparison 20. Sensitivity analysis: Psychotherapy versus CAU (medium‐term)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
20.1 Days of sickness absence Show forest plot	9	1649	Std. Mean Difference (IV, Random, 95% CI)	‐0.15 [‐0.28, ‐0.03]

20.1.1 Low risk of bias	3	768	Std. Mean Difference (IV, Random, 95% CI)	‐0.14 [‐0.41, 0.12]
20.1.2 High risk of bias	6	881	Std. Mean Difference (IV, Random, 95% CI)	‐0.14 [‐0.31, 0.02]

Comparison 20. Sensitivity analysis: Psychotherapy versus CAU (medium‐term)

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Comparison 21. Sensitivity analysis: Improved care versus CAU

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
21.1 Days of sickness absence Show forest plot	6	1912	Std. Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.16, 0.06]

21.1.1 Low risk of bias	2	692	Std. Mean Difference (IV, Random, 95% CI)	‐0.20 [‐0.35, ‐0.05]
21.1.2 High risk of bias	4	1220	Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.08, 0.15]

Comparison 21. Sensitivity analysis: Improved care versus CAU

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Comparison 22. Sensitivity analysis: Improved care versus CAU cluster

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
22.1 Days of Sickness absence Show forest plot	6	1912	Std. Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.16, 0.06]

22.1.1 RCT	5	1724	Std. Mean Difference (IV, Random, 95% CI)	‐0.07 [‐0.19, 0.05]
22.1.2 Cluster RCT	1	188	Std. Mean Difference (IV, Random, 95% CI)	0.09 [‐0.19, 0.38]

Comparison 22. Sensitivity analysis: Improved care versus CAU cluster

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Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

PICO

PICO

Population

Intervention

Comparison

Outcome

Plain language summary

What are the best ways to help people with depression go back to work?

Resumen visual

Authors' conclusions

Implications for practice

Implications for research

Summary of findings

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Patient characteristics and setting

Diagnosis

Exclusion criteria

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of findings and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

Included studies

Designs

Sample sizes

Time period, setting and participants

Interventions

Work‐directed interventions, or work‐directed interventions combined with a clinical intervention

Clinical interventions

Psychological interventions

Psychological interventions plus antidepressant medication

Antidepressant medication

Improved care

Exercise

Art

Diet

Outcomes

Follow up

(a) Short‐term

(b) Medium‐term

(c) Long‐term

Excluded studies

Studies awaiting assessment