Branco 2010.

Methods	Prospective, multicentre, randomised, double‐blind, placebo‐controlled trial with parallel groups. Participants recruited from outpatient centres in Europe 1‐ to 4‐week screening and washout (all FM therapy stopped), 4‐week dose escalation, 12‐week stable dose with target milnacipran 200 mg/day (100 mg twice daily), 9‐day down‐titration, 2‐week follow‐up Data collected using electronic PED: daily PI averaged for 2 weeks immediately preceding visit day Adverse event data collected by spontaneous reporting, non‐leading questions, and clinical evaluation
Participants	Inclusion: age 18 to 70 years, met ACR criteria for FM; physical function (FIQ) ≥ 3, BDI > 25 at screening; mean PI ≥ 40 and ≥ 90 over 14‐day baseline period Excluded: people with various medical and psychiatric conditions or risk factors, considered unlikely to comply with treatment; women not using adequate contraception or pregnant N = 884 Mean age ˜ 49 years, M:F 58:826, mean duration of symptoms ˜ 9.5 years
Interventions	Milnacipran 200 mg/day, n = 435 Placebo, n = 449
Outcomes	PI using 100 mm VAS: 30% improvement from baseline PGIC using 7‐point scale: much or very much improved Composite pain score: 2‐measure BOCF composite responder criteria: 24‐h morning recall pain scores ≥ 30% improvement using 100 mm VAS, PGIC score of 'very much' or 'much' improved Adverse events Withdrawals
Notes	Oxford Quality Score: R = 1, DB = 2, W = 1. Total = 4
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of sequence generation not described
Allocation concealment (selection bias)	Unclear risk	Method not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"In patients receiving placebo, twice‐daily sham dosing was used to maintain blinding"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"In patients receiving placebo, twice‐daily sham dosing was used to maintain blinding"
Incomplete outcome data (attrition bias) All outcomes	High risk	LOCF in analysis of individual outcomes, but BOCF in analysis of composite outcomes
Selective reporting (reporting bias)	Low risk	All relevant outcomes in methods were reported in some way, although not necessarily as our preferred outcome
Size	Low risk	Both groups > 200 participants