Wisner 2015.

Study characteristics
Methods	Study design: RCT, 3‐armed Location: USA Setting: University of Pittsburgh within an academic psychiatry specialty programme in women's health No. of centres: 1 Dates of study: not reported Total duration of study: 8 weeks Recruitment: not reported Randomisation method: stratified by breastfeeding status, infant age (adjusted for gestational age at birth), randomisation tabled created in SAS using a random 3‐ and 6‐block design Analysis by ITT: yes, using LOCF for response and remission and repeated measures mixed linear model for depression severity. Unclear if 1 participant in placebo arm was excluded as they were ineligible and did not receive intervention. Power calculation: study underpowered (stopped early)
Participants	Inclusion criteria: 2‐13 weeks postpartum, score of 18 on Structured Interview Guide for the SIGH‐ADS, Meeting diagnostic criteria for major depressive disorder according to the Structured Clinical Interview for DSM4. Women between 18 and 40 years of age, planning to use or using a non‐estrogen‐containing birth control regimen, without major medical problems, and had normal lipid profiles relative to the postpartum period, nor using other therapies for depression, including antidepressants, psychotherapy, light therapy, or herbal remedies, negative urine drug screen. Breastfeeding women were eligible for inclusion. Exclusion criteria: women with bipolar disorder, a previous psychotic episode, or substance abuse within the last 6 months, heavy smoking, a thromboembolic event, hypercoagulability, current or past history of breast, uterine, or ovarian cancer, or first degree relatives with thromboembolic events Number recruited: 85 Number dropped out: sertraline: N = 8; placebo: N = 7; estradiol: N = 7 Number analysed: 84 or 85 (reporting unclear regarding one woman from the placebo group who was ineligible and should not have been randomised) Age, mean (SD) years: sertraline: 26.2 (5.9); placebo: 27.3 (5.4); estradiol: 26.2 (6.0) Severity of PND: not reported Duration of PND: not reported Physical health co‐morbidities: not reported Mental health co‐morbidities: not reported Ethnicity: % BAME: sertraline: 36.7; placebo: 27.6; estradiol: 46.2 Socioeconomic status: sertraline: < high school: 2/30, high school: 9/30, technical: 13/30, college: 2/30, postgraduate: 3/30; transdermal estradiol < high school: 4/26, high school: 8/26, technical: 8/26, college: 3/26, postgraduate: 3/26; placebo: < high school: 4/29, high school: 6/29, technical: 9/29, college: 8/29, postgraduate: 2/29
Interventions	Women were randomly assigned to 1 of 3 groups Sertraline (30 women) ‐ dosage: day 1 & 2: 25 mg/d, weeks 1 & 2: 50 mg/d; weeks 3 & 4: 100 mg/d; weeks 5 & 6: 150 mg/d; weeks 7 & 8: 200 mg/d; duration: 8 weeks; 100% of women received treatment. 3/30 (10%) discontinued intervention Transdermal estradiol (26 women) ‐ dosage: weeks 1 & 2: 50 mcg/d; weeks 3 & 4: 100 mcg/d; weeks 5 & 6: 150 mcg/d; weeks 7 & 8: 200 mcg/d; duration: 8 weeks; 100% of women received treatment. 5/26 (19%) discontinued intervention. Placebo capsules or patches (29 women) ‐ dosage: 'dosed' in correspondence with respective treatments, 2 capsules daily and 1 or 2 patches per week; duration: 8 weeks; 28/29 women (96.6%) received intervention. 4/29 (14%) discontinued intervention.
Outcomes	Primary outcomes: response (reduction of baseline SIGH‐ADS score by ≥ 50%) or remission (Exit SIGH‐ADS score ≤ 8) Adverse events: Asberg Side Effects Scale
Notes	Funding: NIH Grant R01 MH057102
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Block randomisation, stratified by breastfeeding status and infant age. Randomisation tables created using software
Allocation concealment (selection bias)	Low risk	Patient assigned using software. Randomisation assignment made within the system and stored in a password‐protected part of the database
Blinding of participants (performance bias)	Low risk	All participants received opaque capsules and transdermal patches, with placebo identical to medication. Procedure for maintaining blinding during disbursement of medications reported in detail. Medication monitoring by the study psychiatrist was separate from (and blind to) mood symptom monitoring.
Blinding of personnel (performance bias)	Low risk	Primary study staff blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All evaluators remained blind to the participant's drug assignment until the study was completed.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	"last observation carried forward for the primary outcomes of response and remission," Slightly higher % of participants lost to follow‐up for antidepressant arm (17%) than placebo (10%) or estradiol (8%). Reasons not reported. ITT analysis but using LOCF, so possible bias in favour of antidepressants. Unclear if 1 randomised participant in placebo arm excluded from analysis or not due to being ineligible for study.
Selective reporting (reporting bias)	Unclear risk	No mention of a registered protocol. Trial stopped early
Other bias	Unclear risk	Several authors received financial support and/or compensation from pharmaceutical companies. It is unclear which pharmaceutical company supplied the sertraline preparation used in the study. No data on adherence to medication among completers reported.