Kennard 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 fluoxetine for 12 weeks. Maintenance phase: participants who had an adequate treatment response to fluoxetine randomised to either continue with fluoxetine (antidepressant medication management (MM)) or antidepressant MM + CBT (MM + CBT) for 6 months. Comparison groups: MM + CBT versus MM Duration of relapse prevention phase: 24 weeks (6 months) Follow‐up assessment point of relapse prevention: week 12 defined as baseline for maintenance phase. Every other week from week 12 to 16 and monthly from week 16 to 36, with additional visits allowed when needed. Funded by: National Institute of Mental Health (NIMH)
Participants	Acute phase N = 66 Maintenance phase N = 46 Child and adolescent or adolescent: child and adolescent (11 to 18 years) Depression diagnoses (DSM or ICD) included: a primary DSM‐IV diagnosis of MDD for at least 4 weeks, based on the K‐SADS‐PL, and a score of ≥ 40 on the CDRS‐R Criteria for remission/response: CGI improvement score of 1 (very much improved) or 2 (much improved) and a decrease of at least 50% on the CDRS‐R score Criteria for relapse: a one time CDRS‐R score of ≥ 40, with a 2‐week symptom worsening based on patient and parent report or clinical history or clinical deterioration in which the CDRS‐R score was < 40, but the clinician noted significant deterioration that would suggest full relapse if the patients treatment was not altered Are those at risk of suicide excluded from the trial? Those with 'severe suicidal ideation (active ideation with plan and intent) requiring inpatient treatment' were excluded from the study Suicide risk: N/A as excluded from the study Baseline severity of depression: at baseline of maintenance phase: CDRS‐R mean score (SD): MM = 26.7 (5.1); MM + CBT = 26.5 (5.4) Length of index episode: mean (SD) number of weeks: MM = 35.0 (27.4); MM + CBT = 28.0 (25.1) Number of previous episodes (mean (SD)): MM = 1.2 (0.41); MM + CBT = 1.3 (0.56) Age of onset in years (mean (SD)): MM = 13.3 (2.2); MM + CBT = 13.5 (1.9) Number of comorbidity of the participants (mean (SD)): MM = 1.04 (0.90); MM + CBT = 0.86 (0.83) Age (mean (SD)): MM = 14.4 years (2.2); MM + CBT = 14.3 years (1.7) Sex (M:F): MM = 12:12; MM + CBT = 12:10 Family SES raw score (mean (SD)): MM = 44.9 (14.2); MM + CBT = 48.3 (13.2) Setting: general child and adolescent psychiatry outpatient clinic Psychiatric diagnoses excluded: lifetime history of any psychotic disorder (including psychotic depression), bipolar disorder, anorexia nervosa or bulimia, alcohol or substance abuse within the past 6 months and suicidal ideation requiring inpatient treatment Country: USA
Interventions	Medication (acute phase) N = 66 Name (class and type): fluoxetine (SSRI) Dose (mg/day)/length: 10 to 40 mg/day depending in response for 12 weeks Delivered how: pharmacotherapy visits with a child and adolescent psychiatrist weekly for weeks 1 to 4 and every other week for weeks 5 to 12 Medication management + psychotherapy (MM + CBT) N = 22 Medication name (class and type): fluoxetine (SSRI) Dose (mg/day)/length: 10 to 40 mg/day depending on response Delivered how: by child psychiatrist during regular visits to the clinic Psychotherapy name: relapse‐prevention (RP) CBT. Aims to target residual symptoms that remain after adequate treatment response, and identify and enhance current strengths to promote well being. # sessions/length: 8 to 11 sessions over 6 months (weekly for 4 weeks, biweekly for 2 months and optional booster sessions for 3 months) Manualised (Y/N): yes Individual or group: individual Parent involvement: a minimum of 3 family sessions were included in the protocol Fidelity check: all sessions were audio‐taped. 20.8% of tapes were rated by master's or doctorate‐level therapists on the Cognitive Therapy Rating Scale (Rush 1998). 100% were rated as acceptable. Delivered by: 1 doctoral‐level psychologist, 1 master's level psychologist and 1 post‐doctoral research fellow Medication management N = 24 Content: medication administered as above
Outcomes	Prevention of second or next episode defined as: a one time Children's Depression Rating Scale‐Revised (CDRS‐R; Poznanski 1996) score of ≥ 40, with a 2‐week symptom worsening based on patient and parent report or clinical history or clinical deterioration in which the CDRS‐R score was ≤ 40, but the clinician noted significant deterioration that would suggest full relapse if the patient's treatment was not altered Suicide‐related behaviours: reported as part of adverse events Time to relapse: not reported Functioning: C‐GAS Depressive symptoms on a clinician rated scale: CDRS‐R
Notes	On behalf of Betsy Kennard, Taryn Mayes provided additional data concerning relapse rates (both ITT and observed cases data). ITT data used in meta‐analysis.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"randomisation was stratified by two levels of response: adequate responders, as previously defined...and remitters... Randomization was also stratified by age." pg. 1397‐8
Allocation concealment (selection bias)	Unclear risk	No information
Blinding (performance bias and detection bias) Blinding of outcome assessor	Low risk	"Primary outcome measures were completed at weeks 12 (randomisation baseline), 24, and 36 by IEs who were blind to treatment assignment". pg. 1398
Blinding (performance bias and detection bias) Blinding of participants/care providers	High risk	Unlikely as psychotherapy was being administered
Incomplete outcome data (attrition bias) ITT analysis	Unclear risk	"A Cox proportional hazards regression, with adjustment for CDRS‐R total score at randomisation and for the hazard of relapsing by age across the trial (e.g. absorbing age in the model), was used to compare time to relapse between participants in the MM group and those in the CBT group". pg. 1398
Incomplete outcome data (attrition bias) Number of drop‐outs in each group reported	Unclear risk	Number randomised at acute phase: total = 66 Number of drop‐outs during acute phase: 26 Number randomised at maintenance phase: MM = 24; MM + CBT = 22; total = 46 Number of drop‐outs during maintenance phase: MM = 3; MM + CBT = 3; total = 6 Number analysed at maintenance phase: unclear
Incomplete outcome data (attrition bias) Reasons for drop‐out in each group reported	Low risk	In MM group, 1 dropped out due to a suicide attempt and 2 withdrew consent for additional treatment. In the MM + CBT group, 3 withdrew consent; 1 was feeling better and no longer wanted intervention and 2 sought additional treatment.
Selective reporting (reporting bias)	Unclear risk	Some inaccuracies reporting drop‐out data
Other bias	Unclear risk	Not enough information to make a clear judgement