Keller 1998b.

Methods	Design: RCT Phases: acute (12 weeks), continuation (16 weeks), maintenance (76 weeks) Comparison groups: sertraline vs placebo Funded by: grant from Pfizer (NY)
Participants	Number of participants randomized (NRCT: number of participants included): 161 Criteria for relapse/recurrence: recurrence: DSM‐III‐R criteria for major depression for ≥ 3 weeks; CGI severity score of ≥ 4 (at least moderate severity); CGI improvement score ≥ 3 (minimally improved or less); and an increase in HAM‐D score ≥ 4 points higher than the maintenance baseline; next visit 1 week later in total ≥ 4 weeks of clinical worsening; additionally: senior investigator supporting diagnosis/recurrence. (pp. 1666–7) Age distribution in sample (mean): sertraline: 40.8 (SD 9.0) years; placebo: 42.4 (SD 9.7) years Sex distribution in sample (% women): sertraline: 62.3; placebo: 69.0 Diagnoses in sample: sertraline: 52.0% chronic major depressive disorder, 48.0% double depression; placebo: 43.0% chronic major depressive disorder, 57.0% double depression Depression severity at continuation/maintenance baseline (mean): sertraline: 5.5 (SD 4.2); placebo: 6.3 (SD 3.7) Age of onset (mean): sertraline: 24.9 (SD 11.2) years; placebo: 25.7 (SD 12.5) years Length current/last major episode (mean): sertraline: 88.2 (SD 121.7) months; placebo: 54.9 (SD 80.8) months
Interventions	Maintenance treatment (76 weeks) Sertraline (participants = 77) Name (class and type): sertraline (SSRI) Planned dosage of drug: 50–200 mg/day Dosage of drug (mean): 146.1 mg/day Placebo (participants = 84) Name (class and type): placebo tablets Planned dosage of placebo: unclear Dosage of placebo (mean): 3.4 tablets/day Notes: participants in the placebo arm tapered sertraline by 50 mg reduction per week as placebo substitution. No information about concomitant treatments.
Outcomes	Relapse/recurrence HAM‐D‐24 mean Dropout any SF‐36 Dropout due to adverse event Experiencing any adverse event
Notes	Probably conflict of interest because of funding. They used 2 different criteria for relapse/recurrence, we extracted the stricter one; therefore, maybe less relapse observed than actual happened, in combination with numerous of dropouts with possible bias of results. "Patients meeting recurrence criteria could continue in the study if both patient and study physician agreed that no change in the study medication was indicated at that time. Instead, an increase in daily dose was undertaken at a rate of 50mg/week up to the maximum daily dose of 200mg of sertraline hydrochloride. A similar double‐blind titration was also used for patients receiving placebo treatment." (further details see p. 1667)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information
Allocation concealment (selection bias)	Unclear risk	No information
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind Quote: "To maintain blinding, this group of patients continued (as a parallel but non‐randomised group) receiving imipramine during subsequent continuation and maintenance phases… The integrity of the study's double‐blind component was not compromised." (p. 1666)
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No information
Incomplete outcome data (attrition bias) All outcomes	High risk	70% dropout in the placebo group. The data were replaced by the LOCF ‐method (i.e. 70% of data replaced by last observation point, the participant's condition was probably better at this earlier time).
Selective reporting (reporting bias)	Unclear risk	No information
Other bias	High risk	Insufficient treatment adherence: no information. Allegiance bias/conflict of interest: whole study financed by Pfizer. Attention bias: most likely, each treatment group gained same attention (as both groups received tablets).