Wisner 2006.

Study characteristics
Methods	Study design: RCT, double‐blind Location: USA Setting: no details No. of centres: 3 (Cleveland, Ohio; Louisville, Kentucky; Pittsburgh, Pennsylvania) Dates of study: not reported Total duration of study: 24 weeks; acute phase (8 weeks) continuation phase (16 weeks) Recruitment: not reported Randomisation method: block randomisation with a sequence generated in SPSS Analysis by ITT: yes for primary outcomes (response and remission), LOCF Power calculation: yes
Participants	Inclusion criteria: women aged 15‐45 years with major depression within 4 weeks of birth. Women with chronic depression (an episode on major depression beginning before the index pregnancy) were also included after additional funding was obtained part‐way through the study. Mothers had to present for treatment within 3 months of delivery and score ≥ 18 on the HAM‐D Exclusion criteria: presence of any other Axis I disorder except generalised anxiety disorder or panic disorder, contraindications to TCA treatment, and concurrent psychiatric treatment Number recruited: 109 Number dropped out: 23 from the sertraline group (42%), 13 from the nortriptyline group (24%) Number analysed: ITT and analyses presented for 95 women who took the assigned medication for at least 1 week and provided at least 1 week of follow‐up data and 83 women who provided at least 3 weeks of follow‐up data Age: no data Severity of PND: specific data not reported. Authors stated that "women randomly assigned to SERT versus NTP did not differ on initial HRSD, CGI, GAS, and the SPQ composite score". Duration of PND: not reported Physical health co‐morbidities: not reported Mental health co‐morbidities: not reported Ethnicity: significantly more non‐white women were randomly assigned to sertraline (40%) than nortriptyline (19%) (Fisher exact test; P = 0.02). There were no other demographic differences between the 2 drug groups at baseline Socioeconomic status: not reported
Interventions	Women were randomly assigned to 1 of 2 groups Sertraline: the dosing began with 25 mg/day for 2 days. Thereafter, the dose was increased to 50 mg/day and further increased until either response or side effects prohibited further dose escalation. The maximum dose was 200 mg/day Nortriptyline: initial dose of 10 mg/day. This was then increased to 25 mg/day and then further increased until either response or side effects prohibited further dose escalation. Maximum dose was 150 mg/day
Outcomes	Primary outcomes: response to treatment at 8 weeks (50% reduction in HAM‐D from baseline); remission of depression (HAM‐D < 7 at week 8); continuous change in HAM‐D; severity of symptoms of depression (CGI scale at week 8); overall functioning as measured by the GAS; issues in income, housing, relationships and work (SPQ) Secondary outcome: side effects on the Asberg Side Effects Rating Scale in addition to time to withdrawal due to side effects, obsessions and compulsions measured with the YBOCS, emergence of mania was screening for safety reasons using the Mania Rating Scale (derived from the Schedule for Affective Disorders and Schizophrenia) Time points: weekly intervals for weeks 1‐8, then again at week 24
Notes	This study was funded by the National Institute of Mental Health.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Subjects were randomised 1:1 to either nortriptyline or sertraline in block of 8 to 12 with a sequence generated by SPSS"
Allocation concealment (selection bias)	Unclear risk	No details given on allocation concealment
Blinding of participants (performance bias)	Low risk	"Prescriptions were assembled by the research pharmacist. The nortriptyline and sertraline were delivered in 2 doses, with breakfast and at bedtime. The opaque, inert gelatine capsules contained either sertraline (AM)/placebo(HS) or placebo(AM)/nortriptyline (HS)"
Blinding of personnel (performance bias)	Low risk	"The primary staff (side effects monitor, mood symptom rater, and study psychiatrist) were blind to drug assignment until project completion. The medication monitoring function (nurse) was separate from (and blind to) the mood monitoring (interviewer)"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"The primary staff (side effects monitor, mood symptom rater, and study psychiatrist) were blind to drug assignment until project completion"
Incomplete outcome data (attrition bias) All outcomes	High risk	"Significantly more women who took sertraline compared with nortriptyline withdrew from the study in the first 8 weeks (23/55 [42%] versus 13/54 [24%], respectively [P = 0.02]). The proportion of women who were lost to follow‐up or withdrew by personal choice differed significantly (sertraline, 20%, vs. nortriptyline, 6%; Wilcoxon χ21 = 4.86; P = 0.03). Other reasons for withdrawal (side effects, hypomania occurrence, or clinical deterioration) did not differ between the 2 drug groups" It is unclear why the difference in withdrawal between study groups was so high ‐ but likely to cause bias in results
Selective reporting (reporting bias)	Unclear risk	Protocol unavailable
Other bias	Low risk	"Fourteen women had minimal drug in their blood despite claims of compliance. The results remained the same when data from these 14 women were removed. Drug assignment in the 14 women was distributed similarly between nortriptyline (n = 9/51, 18%) and sertraline (n = 5/44, 11%; Fisher exact test, P = 0.29)"