Study characteristics

Methods

Study Design:Double‐blind randomised trial

Number of trial arms: 4 (3 treatment and one placebo).

Study grouping: Parallel group

Recruitment: unclear. Follow up: 6 weeks.

Lost to follow up: 29.5%

Participants

Participants: 61 were randomised (T1: 38, C: 23).

Inclusion criteria:

‐ DSM‐III diagnosis of depressive disorder
‐ mood reactivity (i.e. significant lifting of mood in response to positive environmental events)
‐ onset prior to age 21 yrs
‐ rated by experienced clinician to be depressed for most or virtually all of the time through adulthood
Baseline characteristics:

Mean age: 35 yrs (SD 8.9)

Female: 52%

Single: 57%

Married: 23%

Divorced or separated: 19.6%

Working: 70%

Setting: Outpatients in New York, USA

Interventions

T1: Treatment with increasing dose of either TCA or MAO
‐ 60 to 90 mg/day of phenelzine (T1a)
‐ 200 to 3000 mg/day of imipramine (T1b)
‐ 40 mg/day of L‐deprenyl (T1c)
Duration: 6 weeks.
C: 4 to 6 placebo pills/day. Duration: 6 weeks

Outcomes

Sickness absence:

1) hours worked in past week (baseline and at 6 weeks). From the LIFE scale.

Depressive symptoms:

1) CGI (measured but not reported!)
2) HAM‐D (measured but not reported!)

Work functioning:
1) work functioning of the LIFE scale (psychosocial functioning part) (baseline and at 6 weeks)

Notes

Country: US

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random sequence generation not reported

"Following baseline evaluation, patients were treated with single‐blind placebo for 1‐2 weeks, those who were still depressed were randomly assigned to 6 weeks of treatment with increasing doses of one of four agents in a double blind design."

Allocation concealment (selection bias)

Unclear risk

Allocation concealment not reported

"Following baseline evaluation, patients were treated with single‐blind placebo for 1‐2 weeks, those who were still depressed were randomly assigned to 6 weeks of treatment with increasing doses of one of four agents in a double blind design."

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

A double blind design was used

"Following baseline evaluation, patients were treated with single‐blind placebo for 1‐2 weeks, those who were still depressed were randomly assigned to 6 weeks of treatment with increasing doses of one of four agents in a double blind design."

Blinding of outcome assessment (detection bias)
Sick Leave

Low risk

Patients reported sick leave in an interview, but were blinded to treatment allocation

"Sick leave was assessed by the LIFE. The LIFE is a semi‐structured interview which tracks episodes of psychiatric illness. The portion of the LIFE which we used assessed the psychosocial functioning during the week in five areas; employment..etc. The LIFE was administered to the patient by the treating physician."

Blinding of outcome assessment (detection bias)
Depressive symptoms

Low risk

Depressive symptoms were determined by personnel, were blinded to treatment allocation

"Clinical outcome was determined by the treating psychiatrist on the basis of Clinical Global Improvement."

Incomplete outcome data (attrition bias)
Depressive symptoms

Unclear risk

Outcome not reported

Incomplete outcome data (attrition bias)
Sick Leave

High risk

Loss to follow up is considered to be high: T1: 28.9%; T2: 30.4%, even though the proportion of incomplete data was comparable in both groups

Selective reporting (reporting bias)

Unclear risk

No design paper or trial registration could be identified to assess this risk

Other bias

Low risk

None Identified

Study characteristics

Methods

Study design: RCT

Recruitment: over 10 months, human resources mailed all potential participants a study information pack.

Follow up: 3 months.

Lost to follow up: overall 40%, subgroup depressed workers: 0%

Participants

Baseline: 53 were randomised (T1: 26; T2: 27). Subgroup of depressed workers: 12.

For the subgroup of depressed workers:

mean age: 50.9 (SD 10.04)

male: 58%

Inclusion criteria: employees of a large communications company absent from work with mild to moderate mental health difficulties for 8 to 90 days authorised by general practitioner certificate

Exclusion criteria: severe or complex disorders (psychosis, comorbid personality disorder), degenerative cognitive disorders, substance misuse or active self‐harm

Setting: large communications company.

Interventions

T1: Telephone CBT, delivered over 12 weeks by one of two registered graduate mental health workers. Participants worked with therapists through regular phone calls to identify and challenge negative thoughts, develop self‐care skills and complete workbook exercises emphasizing behavioural activation. Therapists received 12 h of didactic instruction and role play and weekly supervision from a senior CBT therapist.

T2: Usual care, primary and occupational health services.

Outcomes

Sickness absence

1) self‐reported actual working hours (HPQ) in last four weeks

Depressive symptoms

1) depression, assessed by the HADS

Notes

Country: UK

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Personal communication: "Yes there was a random component in the sequence generation – and the sequence was held by an independent trial units."

Allocation concealment (selection bias)

Low risk

"Randomization was conducted centrally by an independent service, with minimization on age, gender and illness severity". "[...] internal validity was heightened trough allocation concealment via central randomisation [ .. ]"

Blinding of participants and personnel (performance bias)
Sick Leave

High risk

Due to the nature of the intervention, the participants could not be blinded and the control condition (usual care) was deemed less desirable,

Blinding of outcome assessment (detection bias)
Sick Leave

High risk

The actual working hours were assessed by the participants themselves. As they were aware of the allocation status, risk of detection bias is considered to be high

Blinding of outcome assessment (detection bias)
Depressive symptoms

High risk

Depression is assessed by the HADS, which is a self‐reported instrument. As the participants were aware of their allocation status, risk of detection bias is considered to be high

Incomplete outcome data (attrition bias)
Depressive symptoms

Low risk

Personal communication: "For the subgroup of depressed workers, there is no loss to follow up."

Incomplete outcome data (attrition bias)
Sick Leave

Low risk

Personal communication: "For the subgroup of depressed workers, there is no loss to follow up."

Selective reporting (reporting bias)

Unclear risk

No design paper or trial registration could be identified to assess this risk

Other bias

Low risk

None identified

Study characteristics

Methods

Study design: Randomised controlled trial

Study grouping: Parallel group

Number of trial arms: 2

Recruitment: The researchers recruited members from Kaufmännische Krankenkasse (KKH), a statutory health insurance company with about 1.8 million members nationwide. First, to identify participants who were at high risk for sick leave due to depression, insurance members were screened for previous diagnosis of depression (ICD codes F32.0, F32.1, F33.0, F33.1, andF34.1), previous sickness absence due to depression, and current sickness absence. Second, the study team sent an invitation letter to all positively screened insurance members along with study information, the informed consent form, and a 6‐digit code to login into the platform.

Follow‐up: 12 and 24 weeks

Participants

Baseline characteristics

Clinical Intervention: psychological: I‐CBT, I‐guided

• Number of participants randomised: 100

• Gender: 34% male

• Marital status: 24% single, 56% married/partner, 15% divorced/separated, 5% widowed

• Occupation: 22% executive position

• Sick leave status: 25.60 ± 2.03 in past 90 days and average sick leave was 25.60 ± 2.03 in past 90 days

• Age: 47.01 ± 10.36

CAU‐info: Waiting list plus psycho‐education

• Number of participants randomised: 80

• Gender: 29% male

• Marital status: 22.5% single, 57.5% married/partner, 17.5% divorced/separated, 2.5% widowed

• Occupation: 18% executive position

• Sick leave status: 27.69 ± 2.37 in past 90 days and average sick leave was 27.69 ± 2.37 in past 90 days

• Age: 48.66 ± 11.59

Overall

• Number of participants randomised: 180

• Gender: 32% male, 68% female

• Marital status: 23% single, 57% married/partner, 16% divorced/separated, 4% widowed

• Occupation: 20% executive position

• Sick leave status: not reported

• Age:47.74

Inclusion criteria: Insurance members in the insurers database that after screening were adults with a previous episode of mild to moderate depression(International Classification of Disease codes F32.0, F32.1,F33.0, F33.1) or dysthymia (F34.1)

Exclusion criteria: Participants with a score of ≥ 20 on the Patient Health Questionnaire (PHQ‐9), indicating severe depression, were excluded. A second exclusion criterion was suicidality as measured by one item on the presence of suicidal thoughts

Pretreatment differences: PHQ‐9, Gender, relationship status, education, employment, executive position, previous depression, depression medication, being in psychotherapy were tested for group differences, none of these were statistically significant. The authors further state " No clinically relevant differences in terms of any baseline characteristics were found, and we concluded that randomisation was successful."

Setting: Participants were recruited through a statutory health insurance company

Interventions

Intervention characteristics

Clinical Intervention: psychological: I‐CBT, I‐guided

• Content: "The intervention’s psychological approach includes cognitive‐behavioural therapy, mindfulness training, and systemic counselling. During the development process, current research evidence on the respective therapies was used as the basis, and special emphasis was placed on a “person‐based” approach,focusing on the perspectives of the people who would use the intervention. Cognitive‐behavioural therapy is the most extensively researched psychological treatment approach inWeb‐based interventions. From cognitive‐behavioural therapy, the intervention used elements of cognitive restructuring, with an emphasis on dealing with negative moods and automatic thoughts, as well as exercises for behavioural activation. Mindfulness training has been used increasingly in psychotherapy over the past years. It was shown to be effective for depressive symptoms and can be adapted to online formats. The intervention module on mindfulness engages the user in exercises to observe the self and to practice mindfulness in daily situations. Systemic counselling is a therapeutic approach that highlights the social context surrounding the individual and its resources. Specifically, systemic questioning technique sand instructions were employed to make use of the participants’ social support. Systemic principles were presented in specific weekly sessions, while homework exercises on systemic therapy encouraged the participants to adopt a systemic viewpoint and behaviour change in their everyday interactions."

• Duration, frequency, length: 12 weeks, 12 times, 30‐45 minutes each

• Communication means: Web‐based, email, telephone

• Providers: Therapist contact upon request, that is, psychologists (bachelor level or higher) trained in the intervention approach provided feedback via email or telephone

CAU‐info: Waiting list plus psychoeducation

• Content: Wait‐list plus psycho‐education condition. Participants had access to text‐based information on the nature of depression and its symptoms and treatment. The psycho‐education content was developed by a team of trained psychologists (bachelor degree or higher) and was based upon scientific literature on depression. This type of control condition was chosen because more active control groups are considered to be more methodologically valid. The control group did not have access to therapist guidance. Participants were eligible to access the intervention after study completion, if they requested access

• Duration, frequency, length: 12 weeks, supposed to use each week

• Communication means: Web‐based

• Providers: Not applicable

Outcomes

Sickness absence

Days lost in 90 days following randomisation

• Outcome type: Continuous outcome

Depressive symptoms

BDI‐II

• Outcome type: Continuous outcome

Notes

Country: Germany
Outcomes
Absenteeism: Three sickness absence measures were constructed. First, the number of persons who were absent at least once, second, absence frequency as the number of times a person was absent during the 90 day period irrelevant of duration, and third, absence duration as the total number of absence days during the 90 day period. Sickness absence data was not diagnosis‐specific. From the 90 days examined at each time point, participants in the intervention group were absent from work 26 days at baseline and 25 days at post‐assessment. In the control group, participants were absent 28 days at baseline and 24 days at post‐assessment. I have calculated the SD based on the mean diff of 1 and P value of test difference provided by authors (P = 0.88). SD is then 41.62. (based on Cochrane handbook 4.2.5. (8.5.2.4) for differences in means Depression: PHQ data only available at T1 (12 weeks) (BDI was measures at 24 weeks as well)
Outcomes
The numbers are based on random imputation for the BDI. For sickness absence less data were available but the researchers did not use imputation here for unclear reasons. The follow‐up time is unclear. The article states post‐assessment but there have been assessments at 12 weeks and 24 weeks. It is unclear what 24 weeks would stand for because the waiting list group could have the active intervention now. Follow‐up time not stated in protocol.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "We used a computerized block randomisation procedure (allocation ratio 1:1, block size 10)."

Judgement comment: Computer generated

Allocation concealment (selection bias)

Low risk

Quote: "The researcher conducting the randomisation had no information about the participants apart from their 6‐digit codes and did not participate in the enrolment and assignment of the participants to study groups, which was handled by two different researchers."

Blinding of participants and personnel (performance bias)
Sick Leave

High risk

Comment: Participants were not blinded to allocation. 'The control group was a wait‐list plus psycho‐education condition." The control group did not have access to therapist guidance. Participants were eligible to access the intervention after study completion, if they requested access.

Blinding of outcome assessment (detection bias)
Sick Leave

Low risk

Comment: Information on work absenteeism was retrieved from health insurance records. In the German health care system, such standardized health data is collected routinely. Its primary purpose is cost reimbursement and quality assurance, but it can be made available for secondary analysis. Due to the routine data collection, health insurance records are assumed to have high ecological validity.

Blinding of outcome assessment (detection bias)
Depressive symptoms

High risk

Comment: Outcomes were self‐assessed depression

Incomplete outcome data (attrition bias)
Depressive symptoms

High risk

Quote:"Baseline characteristics between participants who completed the post‐assessments and those who were lost to follow‐up were tested for differences. Older participants (PHQ at T1: P=.02, BDI at T2: P=.03) and participants with higher education (PHQ at T1: P=.03, BDI at T2: P=.04) were more likely to complete the post‐assessment on the primary outcome and the follow‐up assessment. Participants who were not in psychotherapy during study enrolment were more likely to complete post‐assessment on one of the primary outcomes"

Comment: There was more than 20% attrition

Incomplete outcome data (attrition bias)
Sick Leave

Low risk

Comment: There was less than 10% attrition

Selective reporting (reporting bias)

Low risk

Quote: "The study was registered retrospectively on February 1, 2013, under the International Standard Randomized Controlled Trial Number ISRCTN02446836; http://www.controlled‐trials.com/ISRCTN02446836."

Judgement comment: All outcomes relevant for this review" improvement of depressive symptoms or symptoms of adjustment disorder (weekly screening by the PHQ‐9; pre‐post measurement with two follow‐ups by the BDI‐II)Secondary outcome measures1. Reduction of sick days (routine data analysis) "were published.In the protocol, EQ‐%D, ASF and SCL‐14 were also listed as secondary outcomes, but these were not published.The trial was set up to also include adjustment disorder. Current incapacity to work certificate was an inclusion criterion in the protocol, but is not mentioned in the publication.

Other bias

Low risk

No other bias detected

Study characteristics

Methods

Study design: Randomised controlled trial

Study grouping: Parallel group

Number of trial arms: 2

Recruitment: Outreach was conducted via the Chestnut EAP call centre, print ads, online postings and ads, email listservs, and flyers. All interested potential participants were directed to an informational website that described the broad characteristics of the study’s purpose, activities, and compensation, concluding with an online screening survey.

Follow‐up: 6 weeks and 10 weeks

Participants

Baseline characteristics

Clinical: psychological: I‐CBT, I‐guided

• Number of participants randomised: 150

• Gender: 25% male

• Marital status: Married/living with partner 78 (52.0%) Divorced 22 (14.7%) Widowed 3 (2.0%) Separated 5 (3.3%) Single 42 (28.0%)

• Occupation: Full time 84 (56.0%) Part time 53 (35.3%) Self‐employed 13 (8.7%)

• Sick leave status: 100%

• Age: 40.6 ±11.5

No intervention or Care as Usual

• Number of participants randomised: 150

• Gender: 21% male

• Marital status: Married/living with partner 72 (48.0%) Divorced 23 (15.3%) Widowed 2 (1.3%) Separated 5 (3.3%) Single 47 (31.3%)

• Occupation: Full time 92 (61.3%); Part time 46 (30.7%); Self‐employed 12 (8.0%)

• Sick leave status: 100%

• Age: 40.7 ± 11.2

Overall

• Number of participants randomised: 300

• Gender: 23% male

• Marital status: Married/living with a partner 50%

• Occupation: Full‐time 87%

• Sick leave status: 10%

• Age:40.6 ± 11.4

Inclusion criteria: (1) 18 years or older, (2) mild‐to‐moderate depressive symptoms as measured by the Patient Health Questionnaire‐9 (PHQ‐9)(score of 10‐19), (3) not currently suicidal or meeting criteria for bipolar or schizo‐affective disorder, (4) employed at least part time, (5) English speaking, and (6) have access to a high‐speed Internet connection.

Exclusion criteria: None specified

Pretreatment: No substantial differences between intervention and control group

Setting: Occupational as part of employee assistance programmes

Interventions

Intervention characteristics

Clinical: Psychological intervention: I‐CBT, I‐guided

• Content: The Mood Hacker responsive mobile Web app was designed to educate users about depression and the benefits of CBT‐based strategies to improve mood self‐management and to activate(1) daily mood and activity monitoring, (2) increased engagement in positive behavioural activities, (3) decreased negative thinking and increased positive thinking, (4) increased practice of gratitude, mindfulness, and strength‐based cognitions and behaviours, and (5) daily practice of these skills to improve depression symptoms and increase resilience to future mood disturbances

• Duration, frequency, length: 6 weeks, daily, up to users

• Communication means: Mobile Web

• Providers: Development of the MoodHacker app was undertaken by a multidisciplinary team of researchers and developers at ORCAS;input was incorporated from experts with extensive experience in CBT‐based self‐management interventions for adults with depression and the benefits of positive psychology

Care as Usual‐info

• Content: Alternative care participants received an email with links to vetted online information about depression from Help Guide, the Mayo Clinic, Mental Health America, and the National Institute of Mental Health; they were encouraged to browse these sites on their own schedule for 6 weeks. The educational links were emailed after the baseline assessment. Participants in the alternative care group were then given access to the MoodHacker program after the 10‐week assessment.

• Duration, frequency, length: 6 weeks, supposedly daily and up to users

• Communication means: Internet sites

• Providers: Provided by researchers who also evaluated the programme

Outcomes

Sickness absence

Days lost in past two weeks due to health reasons

• Outcome type: Continuous Outcome

Depressive symptoms

Patient Health Questionnaire Depression Score

• Outcome type: Continuous Outcome

Notes

Country: US

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "After screening into the study, agreeing to the online informed consent, and submitting the baseline assessment, participants were blocked on race/ethnicity and randomised within block into either (1) treatment intervention group (n = 150), which used the MoodHacker intervention for 6 weeks, or (2) alternative care group (n = 150), which received links to six websites with information about depression."

Judgement comment: "To enhance sample representativeness in each experimental condition, qualified participants were blocked on race/ethnicity and then randomly assigned within each race/ethnicity block to condition—treatment or alternative care—using the random number function in our subject database. Unclear sequence generation, unclear how block randomization was conducted

Allocation concealment (selection bias)

Low risk

Quote: "Emails indicating group assignment and linking participants to the online informed consent form were auto‐generated in the database and sent to participants by a research assistant. Upon"

Judgement comment: Automated mails sent to participants leave little room for change

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

Comment: participants and personnel were not blinded. Unlikely that this will have led to different behaviour that had an effect on the outcome

Blinding of outcome assessment (detection bias)
Sick Leave

High risk

Quote:"All other research team members were blinded and, aside from crisis calls, no research team members had direct interaction with subjects after randomisation."

Comment:Both the outcome 'absenteeism' and depressive symptoms were measured using self‐report. Therefore, the risk of bias due to a lack of blinding of the participants (in this study the outcome assessors) is high. "Productivity loss due to work absence was assessed using the two‐item WLQ Work Absence Module," "Depressive symptomatology was assessed at each assessment point using the self‐reported PHQ‐9 "

Blinding of outcome assessment (detection bias)
Depressive symptoms

High risk

Quote:"All other research team members were blinded and, aside from crisis calls, no research team members had direct interaction with subjects after randomisation."

Comment:Both the outcome 'absenteeism' and depressive symptoms were measured using self‐report. Therefore, the risk of bias due to a lack of blinding of the participants (in this study the outcome assessors) is high. "Productivity loss due to work absence was assessed using the two‐item WLQ Work Absence Module," "Depressive symptomatology was assessed at each assessment point using the self‐reported PHQ‐9 "

Incomplete outcome data (attrition bias)
Depressive symptoms

Low risk

Quote: "Prior to conducting these analyses, we employed the single imputation procedure available in SPSS, version 21.0 (IBM Corp) to account for missing data."

Comment: Only 10/150 in intervention group and 5/150 in the control group missing. Imputation made complete ITT analysis possible. Attrition did not differ by condition

Incomplete outcome data (attrition bias)
Sick Leave

Low risk

Quote: "Prior to conducting these analyses, we employed the single imputation procedure available in SPSS, version 21.0 (IBM Corp) to account for missing data."

Comment: Only 10/150 in intervention group and 5/150 in the control group missing. Imputation made complete ITT analysis possible. Attrition did not differ by condition

Selective reporting (reporting bias)

Unclear risk

Judgement comment: All outcomes listed in the trial register were reported on. However, the trial registration was conducted in 2015, while participants were recruited in 2012‐2013.

Other bias

High risk

Judgement comment: Conflicts of Interest Amelia Birney was the study Principal Investigator. She is employed as a Behavioural Scientist at ORCAS, a health innovation and technology company that creates self‐management programs to improve physical and emotional well‐being. Softwaredevelopment was funded with a Small Business Innovation Research grant, which was designed to stimulate research and product development. Thus, improved versions of MoodHacker are being marketed. Ms Gunn and Mr Russell are no longer employed by ORCAS; they will derive no financial benefit from sales of the MoodHacker app or from publication of this research. MsBirney and Dr Ary remain employees of ORCAS with some potential for financial benefit from sales of the MoodHacker app.

Study characteristics

Methods

Study design: Cluster randomised controlled trial

Study grouping: Parallel group

Number of trial arms: 2

Recruitment: Clusters were recruited through all primary care centres in a region in Sweden; patients were recruited through the health centres by asking all with a probably new diagnosis of depression to participate

Follow‐up: 3 months and 6 months

Participants

Baseline characteristics

Improved Care

• Number of participants randomised: 192

• Number with sick leave: 89

• Gender: 32% male

• Marital status: 67% cohabiting

• Occupation: 73% working

• Sick leave status: on sick leave 51%

• Age: 40.8 ± 15.0

Care as Usual

• Number of participants randomised: 184

• Number with sick leave: 99

• Gender: 26% male

• Marital status: 68% cohabiting

• Occupation: 66% working

• Sick leave status: on sick leave 55%

• Age: 41.6 ± 15.4

Overall

• Number of participants randomised: 376

• Gender: 71% female

• Marital status: 67% cohabiting

• Occupation: 69% working

• Sick leave status: 42% sick leave

• Age: 41

Inclusion criteria: Patients attending 23 different urban and rural PCCs,aged≥18 years, diagnosed with a new ( 1 month) mild or moderate (according to Montgomery‐Åsberg Depression Rating Scale‐Self assessment (MADRS‐S), depression (ICD‐10 diagnosis F32, F33)

Exclusion criteria: Diagnosed with bipolar disorder, psychosis, addiction, or cognitive impairment, not speaking/understanding Swedish

Pretreatment: There were no statistically significant differences between participants in the intervention and control patient groups at baseline concerning age, gender,lifestyle, education, occupation, sick leave, depression symptom scores (MADRS‐S and BDI), or QoL.

Setting: Primary care centres (PCCs) in Sweden.

Interventions

Intervention characteristics

Improved Care: Enhanced Care for depression

• Content: Care as usual plus the intervention. Creating an individual care plan. Person‐centered communication around depressive symptoms based on the patient’s current depression symptom assessment with a self assessment instrument in connection with the regular telephone call, as well as behavioural activation. The care manager had direct and regular contact with the General Practitioner (GP), therapist, or other PCC personnel who were involved in the care of the patient. The care manager did not include any type of psycho‐therapy in her/his care of the patient, but supported the patient and increased the accessibility and continuity of the PCC’s care for the patient, coupled with organizational changes that would facilitate care for the patient with depression.

• Duration, frequency, length: 12 weeks, 6‐8 times, 15‐30 minutes; initial visit one hour

• Communication means: Initial face to face; follow‐up telephone

• Providers: Special care manager, nurse 25% working time

Care as Usual‐ General Practice

• Content: Participants at the control PCCs received care as usual (CAU) according to standard protocol and procedures.The Swedish National Guidelines for Depression and Anxiety Disorders recommend high accessibility and continuity, early next appointment, guided self‐help,cognitive behaviour therapy (CBT) (face‐to‐face or Internet delivered), interpersonal therapy, and/or anti‐depressants first and second steps in a stepped care model.

• Duration, frequency, length: 12 weeks

• Communication means: Not specified.

• Providers: General Practitioner

Outcomes

Sickness absence

Sick leave days

• Outcome type: Continuous outcome

Depressive symptoms

Beck Depression Inventory II

• Outcome type: Continuous outcome

• Scale: BDI II

• Range: 0‐27

• Direction: Lower is better

Notes

Country: Sweden

Authors provided extra information for 6 months sick leave: Number of patients, mean number of days on sick leave from 0 to 6 months: Intervention: n = 89, m = 99.9. SD 68.9 Control n = 99, m = 93.5 SD 65.6

BDI end‐scores extracted from figure in article

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Each stratum was allocated into six blocks consisting of two health care centers, in which one was randomly assigned to implement the care man‐ ager function."

Judgement comment: No information on sequence generation

Allocation concealment (selection bias)

Unclear risk

Judgement comment: Allocation concealment at the level of health care centre is not detailed in the publication nor the trial registration. At the level of individuals, allocation concealment is not applicable as all individuals within the health centre received the same care.

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

Comment: Participants were not blind to the intervention. It is unlikely that they changed there behaviour because they knew they were in the intervention group. The same holds for the providers.

Blinding of outcome assessment (detection bias)
Sick Leave

High risk

Quote:The 3 months assessment at the intervention PCCs was carried out by research personnel unknown to the patient, as it could have been a possible source of bias if the assessment was made by the local care manager. At the control PCCs, the 3 months assessment was administered by a specially trained research nurse.

Comment: Sick leave data are self‐reported by patients

Blinding of outcome assessment (detection bias)
Depressive symptoms

High risk

Quote:The 3 months assessment at the intervention PCCs was carried out by research personnel unknown to the patient, as it could have been a possible source of bias if the assessment was made by the local care manager. At the control PCCs, the 3 months assessment was administered by a specially trained research nurse.

Comment: Depression data are self‐reported by patients

Incomplete outcome data (attrition bias)
Depressive symptoms

Low risk

Comment: It is not completely clear, but the attrition of follow‐up was" Follow‐up data: 147 of the 199 in the intervention group (lost = 23 %) 152 of the 184 in the intervention group (lost = 17 %) total: 299 of the 376 (20%) As electronic patient records were used to gather missing data, risk of bias is low. The attrition rate was low, and through access to the electronic patient records, complementary data especially concerning medication and sick certification were also collected.

Incomplete outcome data (attrition bias)
Sick Leave

Low risk

The same holds for sick leave data

Selective reporting (reporting bias)

High risk

Judgement comment: All outcome measures reported in the trial register are reported in the publication, however the trial was retrospectively registered. "Trial registration: Identifier: NCT02378272. February 2, 2015. Retrospectively registered."Moreover, in the trial registration the MADRS‐S is not mentioned, only the BDI‐II. In the publication MADRS‐S is mentioned as primary outcome alongside the BDI‐II. In the results, the MADRS‐S outcome shows statistically sign results and the BDI does not."There was a substantial reduction of depression scores both in intervention and control groups, but the reduction was significantly greater in the intervention group compared to control group when measured with MADRS‐S, and the difference still progressed during the period 4‐6 months, although the care manager intervention was terminated at 3 months."Depression score reduction measured by BDI‐II did not reach significance. Mean depression score measured by BDI‐II was 0.44 lower (95% CI [‐1.62; 2.50], P = 0.67) at 3 months, and 1.96 lower (95% CI [‐0.19; 4.11], P = 0.07) at 6 months"

Other bias

Low risk

Judgement comment: No other sources of bias detected

Study characteristics

Methods

Study design: Randomised controlled trial

Study grouping: Parallel group

Follow‐up: 13 weeks

Number of trial arms: 2

Recruitment: Participants were recruited consecutively from 2 general care clinics and 2 specialist psychiatric outpatient care clinics.

Participants

Baseline characteristics

Art Therapy + Treatment as usual

• Age: 18‐25:5 (11.6%)/ 26‐35:9 (20.9%)/ 36‐45:14 (32.6%)/ 46‐55:13 (30.2%)/ 56‐65:2 (4.7%)

• Gender: Men 10 (23.3%)

• Marital status: Single 12 (27.9%)/ Single parent 2 (4.7%)/ Cohabiting (spouses, partners) 12 (27.9%)/ Partners with children 12 (27.9%)/ Collective 0 (.0%)/ Live‐apart 1 (2.3%)/ Other 4 (9.3%)

• Occupation: Employment On a temporary basis 2 (5.1%)/ With conditional tenure 18 (46.2%)/ Other forms 12 (30.8%)/ Not applicable 7 (17.9%)/ (n = 4 not reported)

• Sick leave status: Not reported

• Number of participants randomised: N = 43

Treatment as usual

• Age: 18‐25:4 (11.1%)/ 26‐35:11 (30.6%)/ 36‐45:6 (16.7%)/ 46‐55:10 (27.8%)/ 56‐65:5 (13.9%)

• Gender: Men 13 (36.1%)

• Marital status: Single 11 (31.4%)/ Single parent 4 (11.4%) Cohabiting (spouses, partners) 9 (25.7%)/ Partners with children 7 (20.0%)/ Collective 2 (5.7%) / Live‐apart 1 (2.9%)/ Other 1 (2.9%)

• Occupation: Employment On a temporary basis 3 (10.7%)/ With conditional tenure 12 (42.9%)/ Other forms 11 (39.3%)/ Not applicable 2 (7.1%)/ (n = 8 not reported)

• Sick leave status: Not reported

• Number of participants randomised: N = 36

Overall

• Age: 18‐25:9 (11.4%)/ 26‐35:20 (25.3%)/ 36‐45:20 (25.3%)/ 46‐55:23 (29.1%)/ 56‐65:7 (8.8%)

• Gender: Men 23 (29.1%)

• Marital status: Single 23 (29.1%)/ Single parent 6 (7.6%)/ Cohabiting (spouses, partners): 19 (24.1%)/ Partners with children 19 (24.1%)/ Collective 2 (2.5%)/ Live‐apart 2 (2.5%)/ Other 5 (6.3%)

• Occupation: Employment on a temporary basis 5 (7.5%)/ With conditional tenure 30 (44.8%)/ Other forms 23 (34.3%)/ Not applicable 9 (13.4%)/ (n = 12 not reported)

• Sick leave status: Not reported

• Number of participants randomised: N = 79

Inclusion criteria: Eligible participants were adults, aged 18 or over, and outpatients who actively sought help for depression. Inclusion criteria were moderate to severe depression without psychotic symptoms.The participants underwent a clinical interview with a registered psychotherapist before definite inclusion, and further assessment with MADRS‐S to ensure that they fulfilled the inclusion criteria.

Exclusion criteria: Exclusion criteria were recent traumatic events needing trauma treatment, bipolar syndrome, ongoing addiction, psychosis, and cognitive disability.

Pretreatment: There were no significant between‐group differences regarding diagnosis, numbers of depression occasions, comorbidity, gender, age, forms of social life, children at home, and different aspects of employment, education at baseline or other characteristics at baseline.

Setting: General and specialist (psychiatric) care in Sweden (Region Västra Götaland in western Sweden). The health care units were located both in city and in rural areas.

Interventions

Intervention characteristics

Art Therapy + Treatment as usual

• Content: I. Goal‐setting Exercise: Body scan art task: Description of the current situation. II. Here and now art task: Mindful exploration of art media, awareness of bodily and emotional responses elicited by sensory stimulation III. Breathing anchors art task: Body image before and after the mindfulness practice; Raise awareness and explore how breathing affects body experience. IV. Breathing‐space art task: Drawing analogue pictures, explore and raise the awareness of emotional reactions. V. Body scan art task: Color and emotions In‐depth exploration of emotions and state of mind. VI. Inner and outer attention art task: stressful, pleasant event pictures, enhance awareness for reactions to stressful situations and find strategies to cope with reactions. VII. One thing at a time art task: Graphic life‐line, awareness of behaviour patterns and strategies. VIII. Breathing exercise art task: Roles awareness of behaviour patterns and roles. IX. Body scan art task: Description of the current situation, evaluation of treatment and process; the patient’s interpretation of meanings are the focus. X. Review of all images art task: Mandala

• Duration, frequency, length: 10 weeks,1 hour session per week

• Communication means: Face‐to‐face

• Providers: Experienced occupational therapists who applied a manual, which consisted of detailed guidelines based on phenomenological art therapy

Treatment as usual

• Content: TAU consisted of acupuncture, cognitive‐behavioural therapy, electroconvulsive therapy, interpersonal therapy, occupational therapy, pharmacological therapy, physiotherapy, psychodynamic therapy,and supportive therapy

• Duration, frequency, length: For CBT average 10 sessions. Varying for the other therapies between 0 and 10

• Communication means: Face‐to‐face

• Providers: Various providers for TAU: The participants’ regular therapists or physicians planned and performed TAU.

Outcomes

Sickness absence

Sick leave percentage during follow‐up

• Outcome type: Continuous outcome

Depressive symptoms

MADRS

• Outcome type: Continuous outcome

Notes

Country: Sweden

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "A simple randomisation procedure was carried out using a computer‐ generated list of random numbers."

Allocation concealment (selection bias)

Low risk

Quote: "The result of the randomisation was stored in an opaque sealed envelope marked with an ID‐code. The first author performed the randomisation procedure before any contact was established with participants. Each participant was then contacted either by phone or by mail for an appointment with the research assistant (a registered psychotherapist). The research assistant described the procedure in detail to the participant before obtaining written informed consent. The assessment started with an interview to confirm the participant’s diagnosis and level of suicide risk, after which the assessment was completed with the self‐assessment questionnaires. The research assistant then in‐ formed participants about their treatment allocation."

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

Quote: "There were no significant differences between PATd/TAU‐ group and TAU‐group in relation to the frequencies of the TAU therapies that the participants received (see Table 2)."

Judgement comment: Unlikely that the participants would change their behaviour based on the intervention

Blinding of outcome assessment (detection bias)
Sick Leave

High risk

Outcomes were self‐reported and patients judged to report beneficial outcomes after the intervention

Blinding of outcome assessment (detection bias)
Depressive symptoms

High risk

Outcomes were self‐reported and patients judged to report beneficial outcomes after the intervention

Incomplete outcome data (attrition bias)
Depressive symptoms

High risk

Of the total group that was randomised (85), 21 were lost to follow up. Percentage lost to follow‐up: 25%

Incomplete outcome data (attrition bias)
Sick Leave

High risk

Of the total group that was randomised (85), 21 were lost to follow up. Percentage lost to follow‐up: 25%

Selective reporting (reporting bias)

Unclear risk

Judgement comment: 'following a research protocol.' We did not find the info.

Other bias

Low risk

Judgement comment: No other sources of bias detected

Study characteristics

Methods

Study design: RCT, random assignment stratified by presence of personality disorder, past major depressive syndrome and gender; two conditions.

Recruitment: screening by nurse and psychiatrist of consecutive patients referred for acute outpatient treatment.

Follow up: 10 weeks. Lost to follow up: 22%

Participants

Baseline: 95 were randomised (T1: 35; C: 39);

Age: T1: 36 (SD 9.5); C: 36.7 (SD 10.4)

Female: T1: 66%; C: 56%

Stable employment: T1: 71%; C: 82%

Inclusion criteria: age 20 to 65 years, new episode of care, MDD DSM‐IV (SCID) + HDRS at least 20;
Exclusion criteria:: bipolar disorder, psychotic symptoms, severe substance dependence, organic disorder, mental retardation, history of severe intolerance to clomipramine, poor command of French language

Setting: outpatient community mental health centre in Switzerland;

Interventions

T1: Psychodynamic psychotherapy: individual sessions by nurse + clomipramine: 25 mg first day, gradually increasing to 125 mg on fifth day (dosage adjustment allowed). Refusal or severe side effects: 20 to 40 mg citalopram per day. Duration: 10‐week program, frequency psychotherapy sessions not fixed, duration of clomipramine 10 weeks
C: Supportive care: individual sessions: empathic listening, guidance and support. + clomipramine: 25 mg first day, gradually increasing to 125 mg by fifth day (dosage adjustment allowed). Refusal or severe side effects: 20 to 40 mg citalopram per day. Duration supportive care: not fixed, duration clomipramine 10 weeks

Outcomes

Sickness absence

1) number of days of sick leave in 10 weeks
Depressive symptoms:
1) full remission (at most 7 HDRS) (at 10 weeks)
2) severity of depression (HDRS score; GAS) (at 10 weeks)

Work functioning:

1) “adjustment to work” subscale of the modified Health‐Sickness Rating Scale (HSRS).

Notes

Country: Switzerland

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation procedure not reported

Allocation concealment (selection bias)

Unclear risk

Randomisation procedure not reported

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

No blinding but risk of performance bias low as both treatments can be considered equally desirable for patients

"Both treatments involved the same clomipramine protocol and intensive nursing in a specialized milieu. In addition, the amount of structured psychodynamic psychotherapy provided during combined treatment was comparable to the amount of supportive care provided during treatment with clomipramine alone."

Blinding of outcome assessment (detection bias)
Sick Leave

High risk

Outcome assessor for sick leave was blinded, but (non‐blinded) patients had to report the number of sick leave days to them

"The psychologists who made the assessments of hospitalizations, number of days of sick leave, and GAS scores were blinded to each patient's treatment assignment."

Blinding of outcome assessment (detection bias)
Depressive symptoms

High risk

"The individuals who rated the presence and severity of major depression and HSRS scores at ten weeks were not blinded to treatment assignment."

Incomplete outcome data (attrition bias)
Depressive symptoms

High risk

Loss to follow up is high: 22%. Risk of attrition bias due to follow up losses is therefore considered to be high, although multiple analyses were used to study the effect on the findings and the authors conclude otherwise: "Twenty‐one patients (12 in the experimental and nine in the control group, or 22 percent) were excluded from the analysis‐‐four who did not return for treatment (three in the experimental group and one in the control group), three who dropped out against medical advice (two in the experimental group and one in the control group), and 14 who were discharged because they had exclusion characteristics that were not detected at entry, including severe alcohol or drug dependence (five in each group) and adverse effects (two in each group). These patients were not significantly different from the other patients in terms of the main outcome variables at intake. The 74 patients who completed the study were not significantly different from the 21 who were withdrawn or from the group of 95 as a whole. To control for intent to treat, the analyses were repeated with all 95 patients who had been randomly assigned to treatment."

"This finding was unchanged when we repeated the analyses and controlled for age, gender, initial severity of depression, GAS score at intake, compliance and intent to treat"

Incomplete outcome data (attrition bias)
Sick Leave

High risk

Loss to follow up is high: 22%. Risk of attrition bias due to follow up losses is therefore considered to be high, although multiple analyses were used to study the effect on the findings and the authors conclude otherwise: "Twenty‐one patients (12 in the experimental and nine in the control group, or 22 percent) were excluded from the analysis‐‐four who did not return for treatment (three in the experimental group and one in the control group), three who dropped out against medical advice (two in the experimental group and one in the control group), and 14 who were discharged because they had exclusion characteristics that were not detected at entry, including severe alcohol or drug dependence (five in each group) and adverse effects (two in each group). These patients were not significantly different from the other patients in terms of the main outcome variables at intake. The 74 patients who completed the study were not significantly different from the 21 who were withdrawn or from the group of 95 as a whole. To control for intent to treat, the analyses were repeated with all 95 patients who had been randomly assigned to treatment."

"This finding was unchanged when we repeated the analyses and controlled for age, gender, initial severity of depression, GAS score at intake, compliance and intent to treat"

Selective reporting (reporting bias)

Unclear risk

No design paper or trial registration could be identified to assess this risk

Other bias

Low risk

None Identified

Study characteristics

Methods

Study design: Randomised controlled trial

Study grouping: Parallel group

Follow‐up: 12 weeks

Number of trial arms: 2

Recruitment: Community‐based recruitment strategies were used to identify study participants, including flyers in medical waiting rooms, pharmacies and university campuses; newsletters; and contact with potential referral sources (e.g. general practitioners, private psychiatrists and local psychiatric inpatient units). Media interviews and advertisements in social media (e.g. Twitter, Facebook), Google, local newspapers and radio stations were also employed as recruitment strategies.

Participants

Baseline characteristics

Diet

• Age: 37.5 (10.7)

• Gender (% female): 61.8 (21)

• Marital status: not reported

• Occupation (income > $ 80 000): 25.0 (8)

• Sick leave status: not reported

• Number of participants randomised: 33

Social Support

• Age: 43.1 (14.6)

• Gender (% female): 81.8 (27)

• Marital status: not reported

• Occupation (income > $ 80 000): 21.2 (7)

• Sick leave status: not reported

• Number of participants randomised: 34

Overall

• Age: 40.3 (13.1)

• Gender (% female): 71.6 (48)

• Marital status: not reported

• Occupation (income > $ 80 000): 23.1 (15)

• Sick leave status: not reported

• Number of participants randomised: 67

Inclusion criteria: Eligibility criteria included participants who were at screening: aged 18 or over and could provide informed consent;successfully fulfilled the DSM‐IV‐TR diagnostic criteria for a major depressive episode; scored 18 or over on the Montgomery–Åsberg Depression Rating Scale and scored 75 or less, out of a possible score of 104, on a Dietary Screening Tool (DST) modified for Australian food products. The DST was completed to confirm ‘poor’ dietary quality, before enrolment. This screening tool was used to reflect usual daily or weekly intake of specified foods. Broadly defined, participants had to report a poor (low) intake of dietary fibre, lean proteins and fruit and vegetables, and a high intake of sweets, processed meats and salty snacks. If participants were on antidepressant therapy or undergoing psychotherapy, they were required to be on the same treatment for at least 2 weeks prior to randomization. Participants had to be readily available for a 12‐week period and have the ability to eat foods as prescribed, without religious,medical, socio‐cultural or political factors precluding participation or adherence to the diet.

Exclusion criteria: Participants were ineligible if they had: (1) a concurrent diagnosis of bipolar I or II disorder; (2) two or more failed trials of antidepressant therapy for the current MDE; (3) known or suspected clinically unstable systemic medical disorder; (4) pregnancy; (5) commencement of new psychotherapy or pharmacotherapy within the preceding2 weeks; (6) severe food allergies, intolerances or aversions; (7) current participation in an intervention targeting diet or exercise; (8) a primary clinical diagnosis of a personality disorder and/or a current substance use disorder.

Pretreatment: The dietary group had significantly lower scores on the dietary screening tool and the ModiMedDiet score than the social support control group at baseline, primarily due to lower intakes of fruit and higher intakes of extras. Otherwise, groups were well matched on characteristics

Setting: Participants were recruited from two sites: Barwon Health in Geelong and St. Vincent’sHealth in Melbourne (Victoria, Australia)

Interventions

Intervention characteristics

Diet

• Content: The dietary intervention comprised 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. This comprised the ‘ModiMedDiet’, developed by RO and CI, which was based on the Australian Dietary guidelines and the Dietary Guidelines for Adults in Greece and is concordant with our previous dietary recommendations for the prevention of depression. This was provided in adjunction to regular clinical therapy.

• Duration, frequency, length: Seven individual 1 hour dietary support sessions; the first four sessions occurred weekly and the remaining three sessions occurred every 2 weeks.

• Communication means: face‐to‐face

• Providers: Intervention delivered by an Accredited Practising Dietician

Social Support

• Content: Befriending consists of trained personnel discussing neutral topics of interest to the participant, such as sport,news or music, or in cases where participants found the conversation difficult, engaging in alternate activities such as cards or board games, with the intention of keeping the participant engaged and positive. This is done without engaging in techniques specifically used in the major models of psychotherapy. This was provided in adjunction to regular clinical therapy.

• Duration, frequency, length: Seven individual 1 hour sessions the first four sessions occurred weekly and the remaining three sessions occurred every 2 weeks.

• Communication means: face‐to‐face

• Providers: Research assistants (RAs) in this trial completed manual‐guided training and also participated in role‐playing training exercises to ensure consistent delivery of the protocol.

Outcomes

Sickness absence

Days lost from paid work in past 3 months

• Outcome type: Continuous Outcome

Depressive symptoms

MADRS

• Outcome type: Continuous Outcome

• Scale: 6‐point scale

• Range: 0‐60

• Direction: Lower is better

• Data value: Endpoint

Notes

Country: Australia

Communication from study authors: Investigators asked participants the number of sickness absence days taken in the past month. They multiplied by 3 to get results for 3 months.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The randomisation sequence was computer generated by an independent person (OD) using a 2 × 2 block design."

Allocation concealment (selection bias)

Low risk

Quote: "mental health assessments were blind to participants’ group allocations, and the randomisation schedule and coding of group allocations were not, at any time, accessible to the research assistants conducting the assessments, or to the biostatistician (SC). At the conclusion of the baseline appointment, the dietician/befriender would meet privately with the participant and inform them of their group allocation in order to maintain blinding of the research assistants."

Quote: "The sequence was saved to a password‐protected spreadsheet, and groups were coded A and B. The randomisation allocation was managed by the trial dieticians or ‘befrienders’, in order to ensure that the research assistants responsible for"

Blinding of participants and personnel (performance bias)
Sick Leave

High risk

Even though blinding was not possible. The control strategy was designed to make it highly unlikely that patients changed their behaviour. However, as pointed out in a published critique of the study: Molendijk et al. (2018) 'The SMILES trial: do undisclosed recruitment practices explain the remarkably large effect?,' the dietary intervention was positively advertised during recruitment, leading to a high risk of performance bias.

Blinding of outcome assessment (detection bias)
Sick Leave

Low risk

"The research assistants remained blind to condition for the final assessment of the outcomes"

Blinding of outcome assessment (detection bias)
Depressive symptoms

Low risk

"The research assistants remained blind to condition for the final assessment of the outcomes"

Incomplete outcome data (attrition bias)
Depressive symptoms

Low risk

"16.4% lost to follow‐up. But attrition was accounted for in the analyses. To test departures from missing at random (MAR), a weighted sensitivity analysis using the Selection Model Approach was applied to the main outcome findings [43, 44]. Briefly, once data had been imputed under MAR (n = 5), parameter estimates from each imputed dataset were reweighted to allow for the data to be missing not at random (MNAR). The chosen constant values used to add to the imputed missing data to account for MNAR were multiplications of standard error (i.e. 1.6) for main outcome comparison under MAR assumptions. To evaluate the robustness of our findings, different degrees of departure from the MAR assuming plausible values ranging from 10*SE to –8*SE were considered"

Incomplete outcome data (attrition bias)
Sick Leave

Low risk

See depressive symptoms.

Selective reporting (reporting bias)

Low risk

Judgement comment: A trial protocol was published before start of the study. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820. Registered on 29 February 2012. Absenteeism was not included in the protocol, but it was reported in the design paper in BMC Psychiatry.

Other bias

Low risk

Judgement comment: No other sources of bias detected

Study characteristics

Methods

Study design: Randomised controlled trial

Study grouping: Parallel group

Number of trial arms: 2

Recruitment: A total of 90 patients were enrolled between March 2010 and March 2013 at 16 primary care centers (PCCs) located in the south‐west region of Sweden. All patients were assessed by a psychologist/psychotherapist (therapist) and randomised to either Internet‐delivered cognitive behavioural therapy (ICBT) or treatment as usual (TAU)..

Follow‐up: 3, 6 and 12 months

Participants

Baseline characteristics

Clinical: psychological: I‐CBT, I‐guided

• Number of participants randomised: 44

• Number with sick leave: 41

• Gender: 33% men

• Marital status: 60% married

• Occupation: 80% employed

• Sick leave status: 48% last year

• Age: 37.1 ± 12.8

Care as Usual‐GP

• Number of participants randomised: 46

• Number with sick leave: 29

• Gender: 26% men

• Marital status: 61% married

• Occupation: 78% employed

• Sick leave status: 40% last year

• Age: 35.1 ± 9.9

Inclusion criteria: men and women aged 18 years and older with symptoms of depression who attended the study PCCs were recruited by the GPs and nurses. Patients positive to ICBT as a treatment option, who had not recently (last month) started or changed possible antidepressant medication were asked about their willingness to participate in the study; assessed by a psychologist/psychotherapist (therapist), patients had to meet diagnostic criteria for depression according to DSM‐IV (assessed via MINI), have a MADRS‐S score below 35, and have access to a computer with speakers or headphones.

Exclusioin criteria: severe depression (according to a MADRS‐S score 35), a principal diagnosis of anxiety (assessed by the therapist), psychosis, bipolar disorder or hypomanic episode, antisocial personality disorder, substance dependence or alcohol abuse (all of the above assessed by therapists using MINI), medium or high suicide risk (defined as MADRS‐S question 9 > 3p and/or MINI Part B–Suicide > 9p, or previous suicide attempt); other severe mental disorder, cognitive disability or communication difficulties that would prevent participation in the ICBT program (only available in Swedish)

Pretreatment: no significant differences in age, gender, socioeconomic status, medication, severity of depression, quality of life or psychological distress except for use of sedatives (n = 5 [ICBT] versus n = 0 [TAU]; P = 0.049)

Setting: Primary Care Centers ‐ GP

Interventions

Intervention characteristics

Psychological intervention: I‐CBT

• Content: CBT program Depressionshjälpen © consisting of behavioural activation and components of acceptance and commitment therapy. Web page with 7 modules and therapist involvement with telephone calls. All patients in the study could receive usual care

• Duration, frequency, length: 8 to 12 weeks, frequency unclear, length unclear

• Communication means: Internet, email and telephone

• Providers: Licensed psychologists or psychotherapists with training in CBT

Care as usual

• Content: Scheduled contacts with GPs, nurses and other personnel at the PCC, face‐to‐face‐psychotherapy, antidepressants, sick leave certification and combinations of these treatments

• Duration, frequency, length: no restrictions

• Communication means: Face to face

• Providers: general practitioner/ GP, nurse, primary care psychologist/ psychotherapist, other personnel

Outcomes

Sickness absence

Sick leave during follow‐up

• Outcome type: Continuous outcome

Depressive symptoms

Beck Depression Inventory II

• Outcome type: Continuous outcome

Notes

Country: Sweden

Additional information received from the authors: Means of number of sick leave days and standard deviations for 0‐12 months for the intervention and control group: Intervention ‐ Internet ICBT : mean 45.8 days, SD 99.3, Control –CAU: mean 49.4 days, SD 92.8.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

The randomisation was computer generated by the randomisation unit.

Allocation concealment (selection bias)

Low risk

Quote: "The patients were consecutively randomised to either ICBT or TAU by an independent research unit at the University of Gothenburg/Sahlgrenska University Hospital. The randomisation process was performed with all study patients as one group, which concealed the allocation to be from both the PCC personnel and the researchers."

Judgement comment: The authors communicated: The unit set up a telephone service office hours (8‐12, 13‐16) where the primary care research nurse could call. The center put up a computer routine so that the person who answered the phone calls from the research nurses at the different primary care centers could log in to the computer and get the treatment option for the patient. A confirmation letter was also sent for every patient to the research leader.

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

Comment: It is unlikely that participants behaved differently knowing that they belonged to the intervention group as the control condition was equally desirable (scheduled contacts with GPs, nurses and other personnel at the PCC, face‐to‐face‐psychotherapy, antidepressants, sick leave certification and combinations of these treatments).

Blinding of outcome assessment (detection bias)
Sick Leave

High risk

Comment: Self‐reported outcomes but no blinding

Blinding of outcome assessment (detection bias)
Depressive symptoms

High risk

Comment: Self‐reported outcomes but no blinding

Incomplete outcome data (attrition bias)
Depressive symptoms

High risk

Out of 90 participants, 22 were lost to follow‐up =24%. Also 8 control participants crossed over to the intervention group and were counted there as intervention participants

Incomplete outcome data (attrition bias)
Sick Leave

High risk

Out of 90 participants, 22 were lost to follow‐up =24%. Also 8 control participants crossed over to the intervention group and were counted there as intervention participants

Selective reporting (reporting bias)

Low risk

Judgement comment: Study reported in two articles Eriksson 2017 and Hange 2017 but they report different results of the trial. The authors communicated that this was due to analysing only working patients

Other bias

Low risk

No other biases detected

Study characteristics

Methods

Study design RCT. Recruitment: patients were recruited by psychiatrists or by general practitioners.

Follow up: 8 weeks.

Lost to follow up: 8.1%

Participants

Inclusion criteria: all patients fulfilling the DSM‐IV criteria for MDD and having a baseline MADRS total score of at least 30 were eligible for the study.

Exclusion criteria: patients meeting DSM‐IV for primary diagnoses for any axis I disorder other than MDD or those with a history of mania, bipolar disorder, schizophrenia or other psychotic disorder, obsessive‐compulsive disorder, cognitive disorder including mental retardation or personality disorder, patients who met the DMS‐IV criteria for substance abuse or dependence within the past 12 months, or used a depot antipsychotic within 6 months before study inclusion or any antipsychotic or anticonvulsant medications within 2 weeks before the first administration of study medication

Baseline characteristics: 280 were randomised (T1: 138; T2: 142). Setting: outpatient; general or psychiatric practices in France.

Male: T1: 28.3%; T2: 38.0%

Age: T1: 44.1 (SD 10.9); T2: 46.2 (SD 11.1)

Family situation:

T1: 23.9% single; T2: 16.2% single

T1: 49.3% married, living with partner; T2: 50.7% married living with partner

T1: 26.8% separated, divorced, widowed; T2: 33.1% separated, divorced, widowed

Occupational status:

T1: 35.5% unemployed; T2: 29.6% unemployed

T1: 64.5% employed; T2: 70.4%

T1: 4.5% craftsman, tradesman; T2: 7.0% craftsman, tradesman

T1: 9.0% manager; T2: 12.0% manager

T1: 21.3% technician; T2: 30.0% technician

T1: 9.0% workman; T2: 4.0% workman

Interventions

T1: Escitalopram (SSRI) 10 mg daily during the first week, 20 mg per day for the remaining 7 weeks

T2: Citalopram (SSRI) 20 mg/day daily during the first week, 40 mg per day for the remaining 7 weeks

All study medications were provided in identical blister packs of identical capsules administered as one capsule per day, regardless of dose or
treatment group. No adjustment of dosage was allowed

Outcomes

Sickness absence

1) days of sick leave for the 2‐month pre‐study period and for the 8‐week study period (percentage of patients and mean consumption of those patients)

Depressive symptoms

1) depression severity, assessed by the Montgomery‐Asberg Depression Scale (MADRS)

2) remission, defined as the total score MADRS of ≤ 12

3) MADRS‐S, the self‐reported version of MADRS

Notes

Country: France

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Personal communication: "Allocation was random. This includes random allocation using equal block sizes."

Allocation concealment (selection bias)

Low risk

Personal communication: "Allocation was concealed. Investigators allotted patients to a treatment defined by the patient inclusion number. All treatments were prepared and identical, the only difference being the treatment number, corresponding to the allocation table, which was kept by the person who prepared the treatments. The investigators were not aware of the nature of the treatments."

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

Trial is double‐blind: "Those meeting the eligibility criteria were randomly assigned to receive double‐blind, fixed doses of either escitalopram 20 mg daily or citalopram 40 mg daily during 8 weeks, with equal block randomisation at baseline." "All study medications were provided in identical blister packs of identical capsules administered as one capsule per day, regardless of dose or treatment group." Personal communication: "The psychiatrist or GP both included the patient, dispensed the study medication, and did the assessments. Patient and investigator were both blind to the treatment, which were identical in aspect. Since this was not placebo‐controlled, both comparators were active and quite similar, differing only be the presence of 20 mg R‐citalopram in the 40 mg citalopram.This actually reduces the risk of unblinding by recognizable drug effects or side‐effects."

Blinding of outcome assessment (detection bias)
Sick Leave

Low risk

"A standardized form was used by trained investigators to record healthcare services and days of sick leave for the 2‐month pre‐study period and for the 8‐week study period." Since the investigators were blinded, the risk of bias is considered to be low

Blinding of outcome assessment (detection bias)
Depressive symptoms

Low risk

The MADSR was done by investigators who are trained or confirmed in the proper use of the MADSR scores and who were blinded for the allocation status. The MADSR‐S is a self‐reported version, but patients were also blinded for treatment allocation

Incomplete outcome data (attrition bias)
Depressive symptoms

Low risk

Loss to follow up is considered to be low. T1: 4.3%; T2: 10.6%

Incomplete outcome data (attrition bias)
Sick Leave

Low risk

No missing sick leave data: "Valid resource utilization information corresponding to the pre study and study periods was thus available for 280 patients."

Selective reporting (reporting bias)

Unclear risk

No design paper or trial registration could be identified to assess this risk

Other bias

Low risk

None identified

Study characteristics

Methods

Study design: Randomised, double‐blind, flexible‐dose, multinational, clinical trial with a one‐week run‐in period with no treatment. After randomization: two treatment arms

Recruitment: patient were asked to participate by GP. Follow up: 8 weeks. Lost to follow up: 16%

Participants

Inclusion criteria: Patients in primary care, age 18 to 85 yrs, DSM‐IV diagnosis of MDD (current or first), Minimal MADRS score of 18.

Exclusion criteria: History of mania or any bipolar disorder, schizophrenia or any psychotic disorder, Currently suffering from obsessive‐compulsive disorder, eating disorder, mental retardation, any pervasive development disorder, or cognitive disorder (DSM‐IV criteria), MADRS of at least 5 on item 10 (suicidal thoughts), Alcohol or drug abuse problems within the previous 12 months, Having had treatment with: antipsychotics, antidepressants, psychotropics (except zolpidem or stable low doses of benzodiazepines for insomnia), serotonin receptor antagonists, lithium, carbamazepine, valproate, or valpromide, ECT, treatment with CBT or psychotherapy, Being pregnant or breastfeeding, Medications likely to interfere

Baseline characteristics: 293 were randomised (T1: 148; T2: 145).

Setting: primary care at 44 sites in 8 European countries. 

with the study

Mean age T1: 48.4; T2: 46.5

Sex: T1: 75.4% female; T2: 71.2% female

Married or cohabiting: T1: 61.9%; T2: 56%

Employed: T1: 51.5%; T2: 60%

Long‐term sickness absence: T1: 11.1%; T2: 11.2%

Higher education: T1: 9.5%. T2: 11.2%

Interventions

T1: Escitalopram (SSRI): initial 10 mg/day. At week 2 or 4 dose could be increased to 20 mg/day at the investigator's discretion if patient's response was unsatisfactory. After 8 weeks of treatment, 1 week run‐out period. Patients on 20 mg/day were down‐tapered to 10 mg for the first 4 days and placebo the last 3. Patients on lower dose received 7 days of placebo
T2: Venlafaxine XR (SNRI), initially 75 mg/day. At week 2 or 4 dose could be increased to 150 mg/day at the investigator's discretion if patient's response was unsatisfactorily. After 8 weeks of treatment, 1‐week run‐out period. Patients on 150 mg/day were down‐tapered to 75 mg for the first 4 days and placebo the last 3. Patients on lower dose received 7 days of placebo

Outcomes

Sickness absence

1) % of patients on sick leave and average length of sick leave per week (3 months prior baseline and during 8 weeks of study)

2) personal communication; days of sick leave during 8 weeks of study, for workers only

Depressive symptoms

1) MADRS (at 8 weeks)

2) HAM‐D (at 8 weeks)

Notes

Country: UK

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Personal communication with first author: "Patients who met the selection criteria at the baseline visit were assigned to 8 weeks of double‐blind treatment according to a computer‐generated randomization list."

Allocation concealment (selection bias)

Low risk

Personal communication with first author: "The details of the randomization series were unknown to any of the investigators and were contained in a set of sealed opaque envelopes."

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

An economic evaluation was conducted alongside a double‐blind,multinational, randomised clinical trial. Personal communication with first author: "This means that both investigator and patient were blinded regarding allocation to treatment."

Blinding of outcome assessment (detection bias)
Sick Leave

Low risk

"Data at baseline consisted of self‐reported patient questionnaires recording use of healthcare services and days of sick leave ...."

Personal communication with first author: "Patients were blinded regarding allocation to treatment."

Blinding of outcome assessment (detection bias)
Depressive symptoms

Low risk

"Depressive symptoms were assessed by trained raters." Personal communication with first author: "Outcome assessors were blinded for the allocation of patients."

Incomplete outcome data (attrition bias)
Depressive symptoms

High risk

Loss to follow‐up depression data is 15%, which we consider high and no appropriate method has been used to account for attrition.

"Efficacy analyses were conducted on the intention‐to‐treat (ITT) population, which included all randomised patients who took at least
1 dose of double‐blind study medication and who had at least 1 valid post‐baseline assessment of the MADRS total score. The ITT
population thus comprised 146 patients in the escitalopram group and 142 patients in the venlafaxine group. A total of 249 patients (of 293) completed the study."

Incomplete outcome data (attrition bias)
Sick Leave

High risk

Lost to follow‐up sick leave data is 16%, which we consider high and no appropriate method has been used to account for attrition.

"Data at baseline consisted of self‐reported patient questionnaires recording use of healthcare services and days of sick leave.

Of the 293 patients in the trial, valid cost information in the 3‐month pre‐study period was available for 251 patients; for 22 patients in the escitalopram arm and 20 patients in the venlafaxine arm, either the physician or patient did not fill in the resource use questionnaire. Of the 251 evaluable patients, 126 received escitalopram and 125 received venlafaxine. Of these, 245 patients reported valid cost information for the 8‐week duration of the trial (four escitalopram and two venlafaxine patients were lost relative to the pre‐study period).

"Given the very low rate of attrition in the sample during the trial, patients with missing data were unlikely to represent serious bias to the results of the present analysis. As a result, no attempt was made to impute missing data."

Selective reporting (reporting bias)

Unclear risk

No design paper or trial registration could be identified to assess this risk

Other bias

Low risk

None Identified

Study characteristics

Methods

Study design: Randomized controlled trial

Number of trial arms: 4

Recruitment: Through the Swedish Social Securance Agency

Follow‐up: 3 months and 9 months

Participants

Baseline characteristics

Work‐directed intervention combined with clinical intervention:WDI plus ACT

• Age: 47.2 ± 9.2

• Gender: 21.6 % male

• Marital status: not reported

• Occupation: not reported

• Sick leave status: 149.4 ± 102.2

• Number of participants randomised: 90

• Numbers in subgroup of depressed participants only: 27

Care as usual

• Age: 46.9 ± 9.5

• Gender: 25 % male

• Marital status: ‐

• Occupation: ‐

• Sick leave status: 143.2 ± 100.1

• Number of participants randomised: 89

• Numbers in subgroup of depressed participants only: 31

Psychological intervention: ACT

• Age: 46.0 ± 8.2

• Gender: 19.1% male

• Marital status: ‐

• Occupation: ‐

• Sick leave status: 139.6 ± 87.4

• Number of participants randomised: 90

• Numbers in subgroup of depressed participants only: 32

Work‐directed intervention: WDI

• Age: 44.9 ± 8.6

• Gender: 26.7 % male

• Marital status: ‐

• Occupation: ‐

• Sick leave status: 154.4 ± 107.5

• Number of participants randomised: 90

• Numbers in subgroup of depressed participants only: 24

Inclusion criteria: Participants from Stockholm County,Sweden, of working age holding a current employment status of at least 50% (working at least 20 hr per week) and a current SA status between 25% and 100% for the past 1 to 12 months; diagnostic criteria of an anxiety disorder, depression, or stress‐related ill‐health as defined by the diagnostic criteria for exhaustion disorder (according to the ICD‐10, Diagnostic Groups F32, F33, F43.8)

Exclusion criteria: Active suicide ideation, severe depression, history of bipolar disorder or psychosis, substance abuse or dependence,unemployment or self‐employment, and insufficient comprehension of the Swedish language.

Pretreatment: "There were no significant pretreatment differences between the groups on the sociodemographic variables or on the pretreatment outcome measures" Diagnostic groups were also similar between interventions

Setting: A large employer in Sweden in the public sector

Depression Subgroup Analysis: Authors re‐analysed the data for the subgroup of depressed participants only.

Interventions

Intervention Characteristics

Work‐directed intervention combined with clinical intervention: WDI plus ACT

• Content: Combined ACT and WDI intervention with two different therapists

• Duration, frequency, length: Nine intervention sessions/meetings over three months

• Communication means: Face‐to‐face

• Providers: see separate interventions

Care as Usual

• Content: Normal treatment:medical doctor plus psychologist, social worker, physical therapist or nurse

• Duration, frequency, length: 2.7 ± 1.4 appointments with doctor

• Communication means: Face‐to‐face

• Providers: see content

Psychological intervention

• Content: Acceptance and commitment Therapy: six core processes in the ACT‐model:acceptance, mindfulness, defusion, self as context, values, and committed action. The second part of the intervention focused on increasing behaviour repertoire in a valued direction, involving discriminating between rule‐governed (e.g. must do, should do) and avoidant behaviours on one side and those driven by positive reinforcement (want to do)on the other side.

• Duration, frequency, length: Six sessions over three months

• Communication means: Face‐to‐face

• Providers: Licensed clinical psychologists with training in ACT with weekly clinical supervision

Work‐directed intervention

• Content: The Work Directed Intervention aims at the facilitation of dialogue between the participant and the workplace through a series of steps involving the participant and the nearest supervisor. (a) the participant‐interview including six open questions regarding the participant’s perception of causes of SA and factors that may facilitate RTW; (b) the supervisor interview carried out at the workplace (c) the convergence dialogue meeting between the participant and the supervisor, consisting of an analysis of the two former inter‐views aiming at agreeing on a rehabilitation plan.

• Duration, frequency, length: Three meetings over three months

• Communication means: Face‐to‐face

• Providers: Licensed clinical psychologists, behavioural therapist, psychiatric nurse with weekly clinical supervision

Outcomes

Sickness absence

Sick leave days during follow‐up period

• Outcome type: Continuous Outcome

Depressive symptoms

HADS

• Outcome type: Continuous Outcome

Work functioning: work ability index

• Outcome type: Continuous Outcome

Notes

Country: Sweden

Additional information received from authors: data were re‐analysed for the subgroup that scored above the clinical cut‐off score for depression on the HADS only
 

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Judgement comment: No information on sequence generation

Allocation concealment (selection bias)

Low risk

Quote: "Following baseline measurements, a blinded administrator made random allocation in blocks of eight, each block containing two possibilities of each condition."

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

Comment: Unlikely that participants would have behaved differently as a result of the intervention

Blinding of outcome assessment (detection bias)
Sick Leave

Low risk

Comment: Objective outcome sick leave from register

Blinding of outcome assessment (detection bias)
Depressive symptoms

High risk

Comment: Self‐report

Incomplete outcome data (attrition bias)
Depressive symptoms

Low risk

Comment: Loss to follow‐up about 10% across different groups

Incomplete outcome data (attrition bias)
Sick Leave

Low risk

Comment: Loss to follow‐up about 10% across different groups

Selective reporting (reporting bias)

Unclear risk

Judgement comment: Protocol published. Not all secondary outcomes mentioned in protocol reported. Follow‐up times in report pre, post, 3 mo, 9 mo different from protocol 6, 12, 24 and 60 months

Other bias

Low risk

Judgement comment: No other sources detected

Study characteristics

Methods

Study design: Randomised controlled trial

Study grouping: Parallel group

Number of trial arms: 2

Recruitment: participants were recruited via 6 different companies in the Netherlands,2 banking companies, 2 research institutes, 1 security company, and 1 university, through banners and digital pamphlets on the company’s Intranet and via posters. Employees who showed interest in the study received an information leaflet and an informed consent form via email. After participants gave informed consent, they received a link to an online screening questionnaire via email.

Follow‐up: 12 months

Participants

Baseline characteristics

Clinical intervention: psychological intervention: I‐CBT plus Problem Solving Treatment (PST), I‐guided

• Age: 43 ± 8.9

• Gender: 33.6% male

• Marital status: 74.1 in relationship

• Occupation: all are workers; education low: n = 11 (9.5%), middle: n = 31 (26.7%), high: n = 74 (63.8%); working hours, mean (SD): 33.7 (4.8)

• Sick leave status: all not on sick leave

• Number of participants randomised: 116

No intervention

• Age: 43.8 ± 9.6

• Gender: 41.7% male

• Marital status: 78.3 in relationship

• Occupation: all are workers; education low: n =5 (4.3%), middle: n = 37 (32.2%), high: n = 73 (63.5%); working hours, mean (SD): 34.0 (5.3)

• Sick leave status: all not on sick leave

• Number of participants randomised: 115

Overall

• Age: years mean (SD): 43.4 (9.2)

• Gender: females: n = 144/231 (62.3%)

• Marital status: relationship: n = 176/231 (76.2%)

• Occupation: all are workers, education low n = 16 (6.9%), middle: n = 68 (29.4%), high: n = 147 (63.6%); working hours mean (SD): 33.9 (5.0)

• Sick leave status: all not on sick leave

• Number of participants randomised:231

Inclusion criteria: Employees with elevated depressive symptoms as measured by a score of 16 or higher on the Center for Epidemiologic Studies Depression scale (CES‐D) who were not on sick leave (at the time they completed the baseline questionnaire). Access to the Internet and an email address were required

Exclusion criteria: Using medication for depressive symptoms for less than 1 month or if they had a legal labor dispute with the employer

Pretreatment: At baseline there were statistically significantly more men in the control group (41.7%) against 33.6% in the intervention group. Otherwise, there were no relevant differences.

Setting: RCT comparing a web‐based, guided self‐help intervention with care as usual for workers recruited from different companies in the Netherlands

Interventions

Intervention characteristics

Psychological intervention: I‐CBT plus PST, I‐guided

• Content: Happy@Work: a brief Web‐based intervention delivered with minimal guidance; consists of 2 evidence‐based treatments: problem‐solving treatment (PST) and cognitive therapy (CT) [and a guideline for employees to help them to prevent work‐related stress; Web‐based lessons has a different theme, but always follows the same structure: information about the theme, examples, and assignments. Themes of the lessons are introduction of problem solving (lesson 1), problem‐solving methods (lesson 2), changing cognitions (lesson 3), dealing with work‐related problems (lesson 4), social support (lesson 5), and relapse prevention (lesson 6). Happy@Work is a tunnelled intervention, which means that participants can start with a new lesson after they have received feedback on their assignments from a coach.Participants were viewed as treatment completers if they had followed at least the basic information and assignments of PST and CT (completion of lessons 1‐3).

• Duration, frequency, length: Six weeks, weekly with an option of 1 week extra time in case of delay,

• Communication means: Web‐based intervention with minimal guidance

• Providers: participants receive feedback on assignments from a coach; coaches were trained Master’s‐level students in clinical psychology. All coaches used a protocol‐treatment Manual; to ensure treatment fidelity, all feedback was reviewed by a supervisor (AG) before it was placed on the website.

No intervention

• Content: Care as usual group received an email with the randomization outcome only and were advised to consult their (occupational) physician or a psychologist if they wanted treatment for their depressive symptoms. Participants could seek any additional treatment they wanted

• Duration, frequency, length: Six weeks

• Communication means: none

• Providers: none from study point of view

Outcomes

Sickness absence

Sick leave in past 2 months at 6 months follow/up

• Outcome type: Continuous outcome

Depressive symptoms

CES‐D

• Outcome type: Continuous outcome

Notes

Country: the Netherlands

Work performance was measured but this is different from work ability and we did not use it
 

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "random blocks containing 4, 6, or 8 allocations. An independent researcher made the allocation schedule with a computerized random number generator"

Allocation concealment (selection bias)

Low risk

Quote: "The participants were informed about randomisation outcome via email."

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

Comment: Unlikely that the participants would change their behaviour based on the intervention

Blinding of outcome assessment (detection bias)
Sick Leave

High risk

Comment: unblinded and self‐reported outcomes

Blinding of outcome assessment (detection bias)
Depressive symptoms

High risk

Comment: unblinded and self‐reported outcomes

Incomplete outcome data (attrition bias)
Depressive symptoms

Unclear risk

Quote: Missing data were handled by multiple imputation via data augmentation. Data augmentation is an iterative Markov chain Monte Carlo method to generate the imputed values assuming a multivariate normal distribution. Five imputations were used in all analyses and reported in the effectiveness analyses.

Comment: Loss to follow‐up was 60/116 (52%) in intervention group and 65/115 (56%) in the control group at 12 mo follow‐up. Even though acceptable imputation used, it is unclear if this repairs the enormous loss to follow‐up.

Incomplete outcome data (attrition bias)
Sick Leave

Unclear risk

Quote: Missing data were handled by multiple imputation via data augmentation. Data augmentation is an iterative Markov chain Monte Carlo method to generate the imputed values assuming a multivariate normal distribution. Five imputations were used in all analyses and reported in the effectiveness analyses.

Comment: Loss to follow‐up was 60/116 (52%) in intervention group and 65/115 (56%) in the control group at 12 mo follow‐up. Even though acceptable imputation used, it is unclear if this repairs the enormous loss to follow‐up.

Selective reporting (reporting bias)

Low risk

Judgement comment: More secondary outcomes stated in protocol than reported: quality of life, social support and locus of control. Unlikely that this has introduced bias

Other bias

Low risk

Judgement comment: No other sources of bias detected

Study characteristics

Methods

Study design: Two armed RCT.

Recruitment: Between December 2007 and October 2009, participants were referred by occupational physicians from several occupational health services.

Follow up: 18 months. Lost to follow up: 13.7%

Participants

Inclusion criteria: Age 18 to 65, DSM‐IV diagnosis of MDD, Absent from work at least 25% of their contract hours due to their depression. In addition, the duration of the depression had to be at least 3 months or the duration of their sickness absence had to be at least 8 weeks. Finally, there had to be a relation between the depressive disorder en the work situation, that is, work was one of the determinants of depressive disorder and contributed substantially (> 25%), or the depressive symptoms reduced productivity or hindered RTW.

Exclusion criteria: severe alcohol or drug dependence, bipolar disorder, psychotic disorder, depression with psychotic characteristics, indication of inpatient treatment

Baseline characteristics

117 were randomised (T1: 39; T2: 78);

Age: T1: 41.5 (SD 9.6); T2: 43.8 (SD 9.0)

Male: T1: 41%; T2: 53%

Education (years): T1: 13.9 (SD 3.7); T2: 13.5 (SD 3.1)

Martital status: T1: 59% married or living together; T2: 58% married or living together; T1: 23% single; T2: 28% single; T1: 18% divorced or widowed; T2: 14% divorced or widowed

Contract (number of hours): T1: 32.7 (SD 5.8); T2: 35.0 (SD 5.0)

Absenteeism (number of hours): T1: 27.1 (SD 8.8); T2: 27.6 (SD 10.0)

Duration of absenteeism (months): T1: 3.8 (IQR 2.0 ‐ 6.5); T2: 5.0 (IQR 2.8 ‐ 5.0)

Occupational sector: financial or insurance: T1: 54%; T2: 58%; Health care: T1: 18%; T2: 9%; Other: T1: 28%; T2: 33%

Work experience (years): T1: 14.1 (SD 9.6); T2: 15.9 (SD 11.0)

Setting: Outpatient; Department of Psychiatry, Academic Medical Center

Interventions

T1: Treatment as usual: treatment by psychiatric residents in an outpatient university clinic according to a treatment protocol consistent with the APA guidelines. 19 visits consisted of clinical management, including psycho education, supportive therapy and cognitive behavioural interventions. Therapies were supervised on a weekly basis by an experienced senior psychiatrist specialised in depression. If needed, participants received pharmacotherapy according to a protocolised algorithm. If the participant's condition deteriorated and outpatient treatment was no longer deemed adequate, he or she was referred to day treatment or inpatient treatment
T2: Adjuvant occupational therapy: consisted of 18 sessions (nine individual sessions, eight group sessions and a meeting with the employer), and was conducted by two experienced occupational therapists who had received extensive training in the intervention protocol. During the intervention, the occupational therapist frequently communicated with the occupational physician and the resident treating psychiatric. Employees were recruited to work at least 2 hours per week when starting OT, so that employees were able to directly practise the things learned (e.g. new coping strategies) during therapy

Outcomes

Sickness absence

1) work participation, defined in: a) average number of hours of absenteeism over each 6‐month period and b) duration of sick leave due to depression in calender days from the start of treatment until partial (or full) RTW. Time until partial or full RTW was operationalised as the duration of sick leave due to depression in calendar days from the start of treatment until partial (or full) RTW. Partial RTW was defined as working an increment of at least 5 hours (compared with hours worked at baseline), for at least 4 weeks without partial or full recurrence. Full RTW was defined as working the full number of contract hours in own or other work for at least 4 weeks, without partial or full recurrence

Depressive symptoms

1) severity of depression, assessed by the Hamilton Rating Scale for depression (HRSD)

2) depression remission, defined as having HRSD ≤ 7

3) severity of depression, assessed by the Questionnaire Inventory of Depressive Symptoms Self‐Report (StIDS‐SR)

Functioning:

1) at work functioning: weekly self‐report records of work efficiency on a scale 1‐0 and 3 sub scales of WLQ: Output, time, mental‐interpersonal

2) health‐related functioning, 3 subscales of MOS‐SF 36: role limitations due to emotional problems, mental health, role limitations due to physical problems

Notes

Country: The Netherlands

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Randomization was conducted by an independent research assistant, using software based on a minimization randomisation procedure."

Allocation concealment (selection bias)

Low risk

"Randomization was conducted by an independent research assistant, using software based on a minimization randomisation procedure."

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

"Due to the nature of the intervention, neither patients nor therapists could be blinded to the patient's allocation status." However, it is unlikely that patients or providers will have changed their behaviour based on knowledge of the intervention

Blinding of outcome assessment (detection bias)
Sick Leave

High risk

Sickness absence data are measured by the use of self‐report. As patients are not blinded for the allocation status, risk of bias is high

Blinding of outcome assessment (detection bias)
Depressive symptoms

Low risk

"Study assessment were conducted by a psychiatrist and a researcher who where blind to group allocation." As the HRSD is a clinician‐rated instrument, there is a low risk of bias for the HRSD outcome

Incomplete outcome data (attrition bias)
Depressive symptoms

Low risk

Lost to follow up: T1: 15.4%; T2: 12.8% but appropriate imputation methods have been used. "To take potential biased outcomes caused by selective loss to follow up into account, we used multiple imputation (five imputed datasets), which, assuming missing at random for missing values, gives unbiased results with correct SEs."

Incomplete outcome data (attrition bias)
Sick Leave

Low risk

Lost to follow up: T1: 15.4%; T2: 12.8% but appropriate imputation methods have been used. "To take potential biased outcomes caused by selective loss to follow up into account, we used multiple imputation (five imputed datasets), which, assuming missing at random for missing values, gives unbiased results with correct SEs."

Selective reporting (reporting bias)

Low risk

The study protocol is available and all of the study’s pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre‐specified way

Other bias

Low risk

None identified

Study characteristics

Methods

Study design: Randomised controlled trial

Study grouping: Parallel group

Number of trial arms: 2

Recruitment: Via mental health centres and psychiatrists

Follow‐up: 12 and 24 months

Subgroup participants with depression: Authors reanalyzed the data for the subgroup of participants with depression only: At 12 months follow‐up there were 113 participants with depression in the intervention group and 113 in the control group. At 24 months follow‐up these numbers were 113 and 112 respectively. For depression score the were 87 and 77 at 12 months and 87 and 73 at 24 months follow‐up.

Participants

Baseline characteristics

Work‐directed intervention: Individual Placement and Support (IPS)

• Age: 34 ± 10

• Gender: 29% male

• Marital status: 38% married

• Occupation: no info

• Sick leave status: 54% sickness benefit

• Number of participants randomised: 162

• Number with depression: 113

Care as Usual

• Age: 36 ± 11

• Gender: 35% male

• Marital status: 36% married

• Occupation: no info

• Sick leave status: 61% sickness benefit

• Number of participants randomised: 164

• Number with depression: 113

Inclusion criteria: (1) age 18–60 years; (2) diagnosis of affective disorder (International Classification of Diseases, 10th Revision (ICD‐10): F30‐39) or anxiety (ICD‐10: F40‐41); (3) no contact with mental health services for more than the past 3 years; (4) employed or enrolled in education at some time during the past 3 years (this criterion was changed during the trial from originally 2 years); (5) motivated to return to work or education; (6) not ready to return to work within 3 months after inclusion (equal to match group 2 or 311; used by the job centres in Denmark to estimate how far from the labour market people are. Match group 2: able to participate in pre‐vocational training but not able to work and be off public benefits within 3 months. Match group 3: severe long‐term problems; cannot work or participate in pre‐vocational training); (7) able to read and understand Danish and(8) give informed consent.

Exclusion criteria: (1) somatic co‐morbidity causing reduced ability to work; (2) primary large‐scale alcohol or substance abuse and(3) legal guardian or forensic psychiatric arrangements

Pretreatment: The two groups were comparable at baseline

Setting: Participants were recruited from mental health centres (inpatients and outpatients) and private practising psychiatrists within the Capital Region of Denmark, from 1 October 2011 until February 2013 (inclusion period was extended with 5 months)

Interventions

Intervention characteristics

Work‐directed intervention: IPS

• Content: Briefly, the intervention consisted of mentor support and career counselling, providing five basic services: individualised mentor support based on psychiatric knowledge; coordination of services provided; career counselling; impartial help to clarify private economy; and contact with employers to help participants obtain jobs and keep them. Focus was on competitive employment and support was time unlimited

• Duration, frequency, length: The number and duration of contacts depended on the individual needs; most met with their mentor once a week for 1 to 1 ½ hours.

• Communication means: Face to face

• Providers: Mentors had a minimum of 10 years’ experience from mental health services, as nurses, social workers or occupational therapists. Career counsellors had many years of experience from workplace career counselling or human resources in the private sector. Mentors and career counsellors worked closely together.Newly appointed mentors and career counsellors had a 2‐week introduction to working routines and the IPS‐MA method. Team members received monthly supervision provided by a trained psychologists

Care as usual: WD

• Content: Services as offered by the job centres in Denmark, for instance, courses, company internship programs, wage subsidy jobs, skill development and guidance, mentor support or gradual return to employment.

• Duration, frequency, length: Not measured

• Communication means: Not measured

• Providers: See above

Outcomes

Sickness absence

Number returned to work

• Outcome type: Dichotomous outcome

Depressive symptoms

HAM depression score

• Outcome type: Continuous outcome

Notes

Country: Denmark

Return to work numbers and HAM depression score provided by the authors for the subgroup that was diagnosed with depression
 

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "computer‐generated allocation sequence with varying block sizes of 4, 6 and 8,"

Allocation concealment (selection bias)

Low risk

Quote: "concealed from the investigators."

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

Quote: It was not possible to blind participants, mentors, career counsellors or care providers. Outcome assessors and research team were blinded to allocation throughout the trial period, data collection and statistical analysis. Self‐reported online surveys were answered using an identification number enabling the research team to remain blinded. The randomization code was broken when all analyses were completed, and two conclusions had been drawn.

Comment: Unblinded, but unlikely that the knowledge of the intervention will have changed the behaviour of patients or providers.

Blinding of outcome assessment (detection bias)
Sick Leave

Low risk

Comment: Objective outcome from administrative database

Blinding of outcome assessment (detection bias)
Depressive symptoms

High risk

Comment: Subjective self‐reported outcome

Incomplete outcome data (attrition bias)
Depressive symptoms

Low risk

Quote: All analyses were conducted according to the intention‐to‐ treat (ITT) principles. According to the protocol, 10 we would use mixed model with repeated measurements to handle missing data, but we chose to use multiple imputations, since we believed that this would give us a better estimate of the missing values. 28 Predictions were based on variables with full information indicative of missing values; 100 imputations were made. If more than 50% was missing, we chose to report results based on the actual data, but compared these with results based on multiple imputations, both being prone to bias, results did not differ. We had complete data on all register data.

Incomplete outcome data (attrition bias)
Sick Leave

Low risk

Quote: All analyses were conducted according to the intention‐to‐ treat (ITT) principles. According to the protocol, 10 we would use mixed model with repeated measurements to handle missing data, but we chose to use multiple imputations, since we believed that this would give us a better estimate of the missing values. 28 Predictions were based on variables with full information indicative of missing values; 100 imputations were made. If more than 50% was missing, we chose to report results based on the actual data, but compared these with results based on multiple imputations, both being prone to bias, results did not differ. We had complete data on all register data.

Selective reporting (reporting bias)

Low risk

Judgement comment: Protocol published. No differences with adjusted protocol

Other bias

Low risk

Judgement comment: No other sources of bias detected No other sources of bias detected

Study characteristics

Methods

Study design: RCT.

Recruitment: patients were recruited from 55 general practices in Bristol, London, and Warwickshire between October 2005 and February 2008.

Follow up: 8 months. Lost to follow up: 53% for sickness absence and 29% for clinical outcomes

Participants

Inclusion criteria: patients between 18 and 75 who where identified in primary care as having a new episode of depression which was defined as being diagnosed within the 4 weeks preceding referral. Depression was defined as a score of 14 or more on the BDI12 and an ICD‐10 diagnosis of depression using the CIS‐R.

Exclusion criteria: patients treated for depression in the 3 months before the present episode, patients with a history of bipolar disorder, psychotic disorder, alcohol or substance misuse, and those already receiving psychotherapy

Baseline characteristics

297 were randomised (T1: 149; T2: 148). Setting: patients between who where identified in primary care as having a new episode of depression

Female: T1: 69%; T2: 67%

Age: T1: 35.6 (SD 11.9); T2: 34.4 (SD 11.3)

Marital status:

T1: 34% married; T2: 39% married

T1: 50% single; T2: 47% single

T1: 16% separated or divorced or widowed; T2: 15% separated or divorced or widowed

Employment status:

T1: 65% employed; T2: 56% employed

T1: 15% student; T2: 24% student

T1: 20% not in employment; T2: 20% not in employment

Highest educational level:

T1: 65% A level or above; T2: 63% A level or above

T1: 32% other; T2: 33% other

T1: 3% no educational qualifications; T2: 4% no educational qualifications

Setting: primary care

Interventions

T1: Online CBT in addition to usual care: participants receiving online CBT were offered up to ten sessions of 55 minutes, to be completed within 4 months from the date of randomization when possible. Each participant was assigned their own therapist (psychologist) for the duration of the study. Participants and therapists typed free text into the computer, with messages sent instantaneously, using only this means of communication

T2: Usual care from GP while on a 8‐month waiting list for online CBT: participants on the waiting list were not to receive psychotherapy during the study follow‐up period. Those on the waiting list who had still an eligible Beck Depression Inventory (BDI) score after 8 months were offered the intervention at that time

Outcomes

Sickness absence

1) the number of working days lost because of depression (time off work) over 8 months

Depressive symptoms

1) depression severity, assessed by the BDI

2) recovery, defined as a score of less than 10 on the BDI

Notes

Country:UK

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"Randomization was by means of a computer‐generated code, implemented by an individual who was not involved in the recruitment process, and communicated to the participant within 48 h of the baseline interview."

Allocation concealment (selection bias)

Low risk

"Randomization was by means of a computer‐generated code, implemented by an individual who was not involved in the recruitment process, and communicated to the participant within 48 h of the baseline interview." "The allocation was concealed in advance from participants, researchers involved in recruitment, and therapists."

Blinding of participants and personnel (performance bias)
Sick Leave

High risk

Comment: unblinded and the control condition (usual care and waiting list) was deemed less desirable,

Blinding of outcome assessment (detection bias)
Sick Leave

High risk

The number of working days lost because of depression was recorded in a diary by the participants themselves. As participants were aware of their intervention status, risk of bias high

Blinding of outcome assessment (detection bias)
Depressive symptoms

High risk

The BDI is a self‐report inventory. As participants were aware of their intervention status, risk of bias high

Incomplete outcome data (attrition bias)
Depressive symptoms

High risk

Loss to follow up is high: T1: 27%; T2: 32% even though appropriate method has been used to account for these missing data: "Fourth, a sensitivity analysis investigated the effect of missing data with multiple imputation by chained equation methods in Stata." "Analyses imputing missing values suggested that differences in attrition between the groups did not introduce any noticeable bias."

Incomplete outcome data (attrition bias)
Sick Leave

High risk

Loss to follow up is high: T1: 50%; T2: 55% even though appropriate method has been used to account for this missing data: "we imputed missing observations of cost and QALYs using the multiple imputation by chained equation procedure in Stata release 10." "We acknowledge that more complete data would have been available if we had used questionnaires completed face to face or data from practice records. However, the results of the imputation suggest that any information lost is unlikely to have a major influence on the results or conclusions."

Selective reporting (reporting bias)

Unclear risk

No design paper or trial registration could be identified to assess this risk

Other bias

Low risk

None identified

Study characteristics

Methods

Study design: Randomised controlled trial

Study grouping: Parallel group

Number of trial arms: 3

Recruitment: Patients (unclear which) were screened in primary health care centers and further assessed if they scored 10 or above on the PHQ‐9

Follow‐up: 3 and 12 months

Participants

Baseline characteristics

Psychological intervention: I‐CBT, I‐guided

• Age: 42.1% (18‐34 year)

• Gender: 34.2% male

• Marital status: not reported

• Occupation: not reported

• Sick leave status: 7.3% long‐term sick leave

• Number of participants randomised: 317

Care as usual

• Age: 40% (18‐34 year)

• Gender: 45% male

• Marital status: not reported

• Occupation: not reported

• Sick leave status: 5.7% long‐term sick leave

• Number of participants randomised: 312

Clinical intervention: Exercise

• Age: 25% (18‐34 year)

• Gender: 40% male

• Marital status: no reported

• Occupation: not reported

• Sick leave status: 10.4% long‐term sick leave

• Number of participants randomised: 316

Inclusion criteria: For the original trial inclusion:10 or above on the Patient Health Questionnaire‐9 at an initial screening for depression, age (≥18 years), no severe somatic illness, no primary alcohol or drug use disorder, and no psychiatric diagnosis requiring specialist treatment. In this secondary analysis, the trial is restricted to those who were employed at baseline and 3 months and 12 months follow‐up.

Exclusion criteria: none reported

Pretreatment: 10% more women, 7% more employed, 8% less anti‐depressant use in the control group in the sample restricted to employed persons; exercise group younger

Setting: Primary Care

Interventions

Intervention characteristics

Clinical Intervention: Psychological intervention, I‐CBT, I‐guided

• Content: The treatment was based on self‐help text modules, each based on established CBT principles and presenting information on a specific problem area, useful methods to handle it and an online homework report. four of the modules aimed at managing problems related to work and sick leave: social insurance agency—participants on sick leave could receive this module, which included information about the sick leave process and homework assignments about initiating better communication with the authority; returning to work—participants on sick leave also could receive this module about the transition of going back to work, including home‐work assignments about keeping contact with the employer; handling problems at work

• Duration, frequency, length: 12 weeks, weekly assignments, length variable

• Communication means: Internet, telephone

• Providers: Active support from a therapist: a clinical psychologist or last‐year psychology student under supervision

Care as usual

• Content: Primary care standard treatment for depression determined by the patient’s general practitioner. It could for example include antidepressants, counselling with a CBT focus conducted for about 1 hour and group‐based interventions. Twenty‐five percent of patients in this group received no recorded treatment

• Duration, frequency, length: Variable

• Communication means: Variable

• Providers:

Clinical intervention, Exercise, Aerobic exercise

• Content: Within the PE arm, patients were randomly allocated to one of three levels of exercise: ‘light’ (yoga or similar), ‘moderate’ (inter‐mediate level aerobics) and ‘vigorous’ (higher intensity aerobics). In this study, all three groups were analyzed together.

• Duration, frequency, length: 12 weeks, 3 times per week, 60 minutes

• Communication means: Face‐to‐face, individual guidance

• Providers: Qualified personal trainer:, ICB

Outcomes

Sickness absence

On sick leave: Long‐term sick leave past month

• Outcome type: Dichotomous outcome

The authors reported only the percentage of employed participants on long‐term sick leave and the number of events. We recalculated the number of participants based on these numbers and used this as input in RevMan data‐tables. The authors also reported on estimated number of days absent per month, but deemed these estimates to be too imprecise to capture effects over time.

Work functioning: Work ability

• Outcome type: Continuous outcome

• Scale: work ability index

• Range: 0 to 10

• Direction: Higher is better

Notes

Country: Sweden
 

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "patients)"

Quote: "trial research organisation where a <b>computer program generated the group allocation, with the size of the randomization blocks (36</b> patients) being unknown to the"

Allocation concealment (selection bias)

Low risk

Quote: "When the research nurse had entered all assessment data into the study database and confirmed that all inclusion criteria were met, the allocation for the new patient was revealed via the user interface of the database."

Blinding of participants and personnel (performance bias)
Sick Leave

Low risk

Unblinded, but unlikely that patients or providers changed their behaviour based on knowledge of the intervention

Blinding of outcome assessment (detection bias)
Sick Leave

High risk

Comment: Patients' self‐reported and unblinded to intervention

Blinding of outcome assessment (detection bias)
Depressive symptoms

Unclear risk

Depressive symptoms not assessed

Incomplete outcome data (attrition bias)
Depressive symptoms

Unclear risk

Depressive symptoms not assessed

Incomplete outcome data (attrition bias)
Sick Leave

High risk

Comment: Large attrition: PE 30%, ICBT 25%, TAU 37%

Selective reporting (reporting bias)

High risk

Judgement comment: Protocol retrospectively published according to trials register (article says 'preregistered'), no mention of work outcomes; work outcomes constructed after first data‐analysis

Other bias

High risk

Judgement comment: Subgroup analysis of those employed only that were not prespecified

Study characteristics

Methods

Study design: RCT, randomization on the level of patients stratified for referring GP; 3 conditions.

Recruitment: general practices referred patients to the study. CMHNs were employed by local NHS trusts. Follow up: 26 weeks.

Lost to follow up: 26%

Participants

Inclusion criteria: age: 18‐65; new episode of anxiety, depression or reaction to life difficulties; minimum duration symptoms: 4 weeks; maximum duration symptoms: 6 months; GHQ‐12 score at least 3
Exclusion criteria: patient already in contact with psychiatric services; Patient already receiving psychological treatment; Severe mental illness such as schizophrenia, manic‐depressive psychosis; severe substance misuse, dementia or severe depression with active suicidal ideas; housebound patients; patients without the spoken and written language skills necessary to participate; seriously ill and terminally ill patients; temporary residents

Baseline characteristics

247 randomised (T1: 90; T2: 79; T3: 78)

Mean age: T1: 35.8 (SD 10.92); T2: 34.2 (SD 11.33); T3: 34.9 (SD 11.77)
Female: T1: 72%; T2: 70%;T3: 69%
Married or cohabiting: T1: 60%; T2: 58%; T3: 48%
Fulltime or part‐time employed: T1: 66%; T2: 75%; T3: 69%

Setting: community mental health, UK.

Interventions

Improved care by additional community health nurses

T1: CMHN problem‐solving treatment
1. explanation of treatment and rationale
2. clarification and definition of problems
3. choice of achievable goals
4. generations of alternative solutions
5. selection of preferred solution
6. clarification of necessary steps to implement solution
7. evaluation of progress; Initial 1‐hour session + 5 follow‐up sessions of 30‐45 minutes.
T2: Generic CMHN; nurses were asked to use whatever treatment they were experienced in giving; initial 1‐hour session + 5 follow‐up sessions of 30 to 45 minutes. Range 0 to 8 sessions
T3: GP care: usual care, but asked not to refer patients to a psychological therapist during the study period unless absolutely necessary

Outcomes

Sickness absence
1) number of days off paid work
Depressive symptoms
1) CIS‐R
2) HADS‐D
Work functioning

1) SAS, however, sub‐scale "work outside the home" not separately reported

Notes

Country: UK

Personal communication: data for depressed sub‐sample was provided. In our analyses, the two CMHN subgroups were combined, leaving two study arms.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

"The telephone randomization service at the university of York was contracted."

Allocation concealment (selection bias)

Low risk

"Remote central randomization was provided by telephone"

"Randomisation sequences were in block sizes of either three or six, to prevent practitioners from guessing to which arm the next referral would be."

Blinding of participants and personnel (performance bias)
Sick Leave

High risk

High risk for the comparison with the GP usual care group (T3) as this treatment cannot be considered equally desirable as T1 and T1 for patients and patients were not blinded. "Table 16: n = 50 received their preferred treatment; n = 114 did not receive their preferred treatment; n = 83 reported no preference"

Blinding of outcome assessment (detection bias)
Sick Leave

High risk

Sick leave was measured by self‐report and patients were not blinded to treatment allocation

"Number of days off paid work was captured by a resource‐use questionnaire filled out by patients."

"Patients were reminded not to reveal their allocation at the follow‐up assessments."

Blinding of outcome assessment (detection bias)
Depressive symptoms

High risk

Depression symptom score (CIS‐R and HADS‐D) were measured by self‐report and patients were not blinded. "The computerised version of the CIS‐R, which is self‐complete, was used in this study." "Patients were reminded not to reveal their allocation at the follow‐up assessments."

Incomplete outcome data (attrition bias)
Depressive symptoms

High risk

Loss to follow up is considered to be high (26%). Risk of attrition bias due to follow‐up losses is therefore considered to be high, although sensitivity analyses were conducted and the authors conclude otherwise; "sensitivity analyses were conducted to see whether the result changed depending on what assumptions were made about the missing data". "Table 12 shows that the main findings are not particularly sensitive to the different assumptions about missing data that were investigated."

It was harder to retain patients in the GP care (thus higher loss to follow up in that group): "Although the overall follow‐up rates were good, there was a lower follow‐up rate in the GP arm. It is difficult to tell whether this biased the findings in a particular direction. Follow‐up rates were better among those patients who received the treatment they preferred, so it is likely that there were more disaffected patients in the GP care arm. However, it is not known whether those who dropped out remained more symptomatic than those who were followed up. Failing to receive their treatment of preference was not associated with a worse outcome on the CIS‐R among those who were followed up. The sensitivity analyses suggest that CMHN care, whether generic care or specific PST, is unlikely to be more effective than GP care, unless one believes the LOCF analysis and makes the extreme assumption that all the dropouts remained as symptomatic as they were at the time of last assessment."

Incomplete outcome data (attrition bias)
Sick Leave

High risk

Loss to follow up for sick leave data is considered to be high (26%). Risk of attrition bias due to follow‐up losses is therefore considered to be high, although sensitivity analyses were conducted and the authors conclude otherwise; "cost results from this analysis were validated by substituting where possible data from the GP case notes in place of imputed values for missing data, and repeating the analysis. Overall, the results did not change significantly."

"36% had at least one resource item missing over the 6‐month follow up. Therefore, complete resource use data were available for 159 (64%) of the patients. The results presented here are based mainly on the 184 patients for whom complete CIS‐R data were available over the 6‐month period. To achieve this sample, 25 (14%) of the patients who had CIS‐R data but not resource‐use information had to be imputed. The results were then compared with those obtained using data from GP notes where available instead of imputation, and those obtained using only the 159 patients with complete resource‐use data. After imputing missing values for the 25 patients with missing resource‐use data, the numbers of patients included in the economic analysis in each group were as follows: 51 patients in GP care (28%), 62 patients in generic CMHN care (34%) and 71 patients in PS CMHN care (38%)."

Selective reporting (reporting bias)

Low risk

No indication for selective reporting could be identified. However, in the design study, the comparisons of T1 with T2 was not pre‐specified

Other bias

Low risk

None identified

Study characteristics

Methods

Study design: Randomised controlled trial

Study grouping: Parallel group

Follow‐up: At 3 and 6 months after start of the intervention

Number of trial arms: 2

Recruitment: Information about the trial was provided on the municipality web pages, in local newspapers, and on local radio. All GPs in the catchment areas were informed through an information letter from the National Institute of Public Health and directly by the service providers at local GP association meetings. All clients contacting PMHC in Sandnes and Kristiansand, both GP‐ and self‐referred, got an appointment for individual assessment at the PMHC clinic. In this detailed screening and assessment, one of the therapists conducted a clinical interview with the client. The therapist identified the relevance and severity of the mental health problems, the available client resources, and motivation for treat‐ment. The client received information about the study and the treatment methodology within PMHC. To minimize the nocebo effect, comprehensive information about the rationale for randomisation was provided. The therapist then reviewed all information and decided on inclusion/exclusion in consultation with the client.

Participants

Baseline characteristics

Enhanced care

• Age: 34.6 (SD 11.8)

• Gender Female: Female 65.7%

• Marital status (having a partner): Having a partner 55.1%

• Occupation (having regular work): N.R.

• Sick leave status (functional status): N.R.

• Number of participants randomised: 463

• Number depressed participants only randomised: 417

Care as Usual

• Age: 35.3 (SD 13.1)

• Gender Female: Female 68.4%

• Marital status (having a partner): Having a partner 58.9%

• Occupation (having regular work): N.R.

• Sick leave status (functional status): N.R.

• Number of participants randomised: 219

• Number depressed participants only randomised: 199

Overall

• Age: 34.8 (SD12.2)

• Gender Female: Female 66.5%

• Marital status (having a partner): Having a partner 56.3%

• Occupation (having regular work): N.R.

• Sick leave status (functional status): N.R.

• Number of participants randomised: 774

• Number depressed participants only randomised: 616

Inclusion criteria: PHQ‐9/GAD‐7 scores above cutoff level; being 18 years of age or above and a resident in one of the pilot site municipalities; basic verbal and oral Norwegian proficiency

Exclusion criteria: Entitled to secondary care services due to eating disorder, suicide risk, bipolar disorder, severe depression, invaliding anxiety, psychotic symptoms, severe substance abuse, personality disorder, two or more previous treatment attempts without effect, or serious physical health problem as prime problem

Pretreatment: Not tested, authors: "As displayed in Table 2, baseline demographic and clinical characteristics were generally similar across the two treatment groups".