Clauw 2013.

Methods	Double‐blind randomisation to placebo or continuing on milnacipran 50 to 200 mg ‐ the established daily dose for individual participants. Participants recruited from 58 centres in the United States There was a 4‐week maintenance phase, a 12‐week randomised withdrawal phase, and 1 week of tapering
Participants	Adults meeting the 1990 ACR criteria for FM entered directly from a long‐term, open‐label, flexible‐dose, lead‐in study in which they received milnacipran 50 to 200 mg/day for up to 3.25 years. They had previously received up to 15 months of treatment with milnacipran 100 or 200 mg/day during double‐blind studies resulting in up to 4.5 years of milnacipran exposure before entering the discontinuation study. Participants had to be classified as responders (≥ 50% pain improvement after long‐term treatment) and be receiving a minimum of milnacipran 100 mg/day
Interventions	Milnacipran 100 or 200 mg/day, n = 100 Placebo, n = 51
Outcomes	Loss of therapeutic response, defined as time from randomisation to the first double‐blind study visit in which a participant had < 30% reduction in VAS pain from pre‐milnacipran exposure or worsening of FM requiring alternative treatment, as judged by the study's principal investigator PGIC Quality of life (SF‐36)
Notes	Oxford Quality Score: R = 2, DB = 2, W = 1. Total = 5. Note, though, that this score is not designed for EERW trials
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer generation implied
Allocation concealment (selection bias)	Low risk	Remote allocation using "interactive voice and/or web response system"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Medication "sealed and coded to maintain the double‐blinding"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Medication "sealed and coded to maintain the double‐blinding"
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	LOCF imputation for missing data
Selective reporting (reporting bias)	High risk	Participants who did not experience loss of therapeutic response or withdrew for other reasons were censored in the primary efficacy analysis
Size	Unclear risk	50 to 200 participants per treatment arm