Cheung 2008.

Methods	Design: treatment of individuals after remission/recovery from an acute episode of depression to prevent relapse/recurrence Phases: acute phase: participants treated with sertraline for 12 weeks. Continuation phase: participants that responded to acute phase treated with sertraline for 24 weeks. Maintenance phase: participants who maintained response during continuation phase, randomised to receive either treatment with sertraline or placebo for 52 weeks. Comparison groups: sertraline versus placebo Duration of relapse prevention (termed maintenance in trial) phase: 52 weeks Follow‐up assessment point of relapse prevention: from the maintenance phase, participants assessed weekly for first 4 weeks, then assessed every 2 weeks up to week 52 Funded by: the Canadian Institute of Health Research (CIHR)
Participants	Acute phase N = 93 Maintenance phase N = 22 Child and adolescent or adolescent: adolescent (13 to 19 years) Depression diagnoses (DSM or ICD) included: MD as determined by a clinical interview using the K‐SAD‐PL and scoring > 16 on the first 17 items of the HAM‐D Criteria for remission/response: 2 consecutive HAM‐D scores of < 9 and greater than a 50% reduction in HAM‐D score within 12 weeks Criteria for relapse: defined by clinical judgement of treating physician or if an intervention beyond that permitted by the study protocol was required Are those at risk of suicide excluded from the trial? Not stated Suicide risk: not stated Baseline severity of depression (acute phase): mean (SD) HAM‐D score: total = 20.7 (3.9); sertraline = 21.3 (4.1); placebo = 19.9 (3.8) Length of index episode: not stated Number of previous episodes (% of participants): total = 14%; sertraline = 23%; placebo = 0% Age of onset: not stated Comorbidity of the participants (by group): comorbid anxiety disorder: total = 23%; sertraline = 23%; placebo = 22% Mean (SD) age: at maintenance phase: sertraline = 15.2; placebo = 16.3 Sex (M:F): sertraline = 3:10; placebo = 2:7 Family SES: not stated Setting: outpatient mood disorders clinics in 3 tertiary care centres Psychiatric diagnoses excluded: past or current hypomanic or manic episodes, current psychotic symptoms, substance dependence in the last 3 months Country: Canada
Interventions	Medication N = 13 Name (class and type): sertraline (SSRI) Dose (mg/day)/length: 25 to 200 mg/day, depending on response. During maintenance phase no treatment changes were permitted. Delivered how: by treating clinician every 2 weeks Placebo N = 9 Delivered how: by treating clinician every 2 weeks Content: participants previously treated with sertraline who were randomised to receive placebo pill intervention had their sertraline tapered by 25% of the initial dose every week for the first 4 weeks of the maintenance phase. During maintenance phase no treatment changes were permitted.
Outcomes	Prevention of second or next episode defined by: clinical judgement based on depressive symptoms and functional impairment Suicide‐related behaviours: reported as part of adverse events Time to relapse: recorded as weeks in table 1 Functioning: not a trial outcome Depressive symptoms on a clinician rated scale: HAM‐D
Notes	*All demographics describe the 22 participants included at the baseline of the maintenance phase, unless otherwise specified. 6 participants discontinued the study during the acute and continuation phases due to adverse effects. Reasons for drop‐out were: agitation and hostility (n = 2), psychosis (n = 1) and mania (n = 3).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was conducted by the study pharmacist using a computer‐generated randomisation schedule". pg. 390
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding (performance bias and detection bias) Blinding of outcome assessor	Low risk	"...clinicians and research staff remained blinded to treatment during the randomisation phase". pg 390
Blinding (performance bias and detection bias) Blinding of participants/care providers	Low risk	"Participants...remained blinded to treatment during the randomisation phase". pg 390
Incomplete outcome data (attrition bias) ITT analysis	Low risk	"Subjects who were randomised and received at least one dose of treatment/placebo were included in the analyses". pg 391 Imputation: all drop‐outs considered as recurred in analysis (Figure 1. pg. 390)
Incomplete outcome data (attrition bias) Number of drop‐outs in each group reported	Low risk	Number randomised in maintenance phase: sertraline = 13; placebo = 9; total = 22 Number of drop‐outs during maintenance phase: sertraline = 1; placebo = 2; total = 3 Number analysed post‐maintenance phase: sertraline = 13; placebo = 9; total = 22
Incomplete outcome data (attrition bias) Reasons for drop‐out in each group reported	Low risk	Sertraline: 1 participant lost to follow‐up Placebo: 1 participant lost to follow‐up and 1 withdrew consent
Selective reporting (reporting bias)	Unclear risk	Authors reported on specified outcomes. No access to protocol.
Other bias	Unclear risk	Small sample size limits generalisation. Only included adolescents with MDD and did not capture the full spectrum of depressive disorders present in this age group.