Mease 2009.

Study characteristics
Methods	Design: parallel Duration: 27 weeks Assessment: baseline, 15 weeks, post‐intervention Country: USA
Participants	Pain condition: fibromyalgia Population: adults with fibromyalgia Minimum pain intensity: ≥ 50 on 0‐100 scale Inclusion criteria Aged 18‐70 with fibromyalgia meeting ACR criteria Pain intensity of ≥ 50 on 0‐100 scale Exclusion criteria Physical and mental health comorbidities Total participants randomised: 888 Age in years (mean, SD): 49.5 Gender: 849/888 were female Pain duration in years (mean, SD): 5.6
Interventions	Placebo n = 223 Inert Identical appearance and matched dosing Milnacripran 100 mg n = 224 SNRI Fixed dose Milnacripran 200 mg n = 441 SNRI Fixed dose
Outcomes	Pain intensity Moderate pain relief Substantial pain relief PGIC AEs SAEs Withdrawal
Missing data methods	ITT with LOCF, sensitivity analyses with BOCF
Funding source	Pharmaceutical: supported by Forest Laboratories, Inc., New York, New York, and CypressBioscience, Inc., San Diego, California, USA
Conflicts of interest	Dr Mease has received research grant support from Pfizer Inc, Cypress Bioscience, Inc., Forest Laboratories, Inc., Eli Lilly and Company, Allergan, Wyeth Pharmaceuticals, Jazz Pharmaceuticals, and Fralex Therapeutics. Dr Clauw has received grant support from Cypress Bioscience, Inc. and serves as a consultant to Cypress Bioscience, Inc, Forest Laboratories, Inc., Pierre Fabre Medicament, Pfizer Inc, Eli Lilly and Company, Wyeth Pharmaceuticals, and Proctor and Gamble. Dr Mease was an investigator of this study and a consultant; Dr Clauw was a consultant for this study. As consultants, Drs Mease and Clauw were involved in the study design, analysis of results, and preparation of the manuscript. Drs Gendreau, Rao, and Kranzler are employees of Cypress Bioscience, Inc. Drs Chen and Palmer are employees of Forest Laboratories, Inc
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomisation methods not specified
Allocation concealment (selection bias)	Unclear risk	Allocation procedure not specified
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind with study drugs identical and matched dosing
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Self‐reported outcomes from blinded participants
Incomplete outcome data (attrition bias) All outcomes	High risk	Very high attrition rate, especially for the high‐dose milnacipran. Use a mix of imputation methods including LOCF, BOCF and completers, but not all of the data for this are presented in the paper Attrition Total: 376/888 (42.3%) Placebo: 78/223 (35.0%) Milnacipran 100 mg: 96/224 (42.9%) Milnacipran 200 mg: 202/441 (45.8%)
Selective reporting (reporting bias)	Unclear risk	No protocol or trial registration found
Other bias	Low risk	No other sources of bias were identified.