Clauw 2008.

Study characteristics
Methods	Design: parallel Duration: 15 weeks Assessment: baseline and post‐intervention Country: USA
Participants	Pain condition: fibromyalgia Population: adults with fibromyalgia Minimum pain intensity: ≥ 40 on 0‐100 VAS Inclusion criteria Aged 18‐70 with a diagnosis of fibromyalgia as per ACR ≥ 40 on 0‐100 pain intensity VAS ≥ 4 on physical function component of FIQ Exclusion criteria Current physical or mental health condition Previous exposure to milnacipran Total participants randomised: 1207 Age in years (mean): 50.2 Gender: 1151/1207 were female Pain duration in years (mean): 9.7
Interventions	Placebo n = 405 Inert Matched dosing with identical appearance Milnacipran 100 mg n = 401 SNRI Fixed dose, titrated over 6 days Sham escalation to match 200 mg arm Milnacipran 200 mg n = 401 SNRI Fixed dose, titrated over 6 days
Outcomes	Pain intensity Moderate pain relief Physical function Mood Quality of life Sleep PGIC AEs SAEs Withdrawal
Missing data methods	ITT with LOCF and BOCF
Funding source	Pharmaceutical ‐ Forest Research Institute, Inc. and Cypress Bioscience, Inc.
Conflicts of interest	This research was financially supported by Forest Research Institute, Inc., Jersey City, New Jersey, and Cypress Bioscience, Inc., San Diego, California. The study drug was manufactured by Pierre Fabre Medicament, Boulogne, France. Drug supply and data collection were managed by Forest Research Institute. The study was designed and conducted under the supervision of Drs Gendreau, Palmer, and Clauw. The manuscript was prepared with the editorial assistance of Prescott Medical Communications Group, Chicago, Illinois, under the supervision of Dr Clauw. Dr Clauw has received grant support from Cypress Bioscience, Inc., and serves as a consultant to Cypress Bioscience, Forest Laboratories, and Pierre Fabre Medicament, all of which are involved in the development of milnacipran for fibromyalgia. He also acts as a consultant to Eli Lilly and Company, Pfizer Inc., Procter & Gamble, and Wyeth Pharmaceuticals. He has owned stock in Cypress Bioscience. Dr Mease has received research grant support from Allergan, Inc.; Cypress Bioscience; Forest Laboratories; Fralex Therapeutics Inc.; Jazz Pharmaceuticals; Eli Lilly; Pfizer; and Wyeth. Drs Palmer and Wang are employees of Forest Research Institute and own stock in Forest Laboratories. Dr Gendreau is an employee of Cypress Bioscience and owns stock in that company.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation lists for each site were generated by a computer program.
Allocation concealment (selection bias)	Low risk	Assignments made via an interactive voice response system
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind, matched dosing, and identical appearance of tablets
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	High attrition rates, did not adhere to the mentioned plan with handling and reporting missing data Attrition Total: Placebo: 115/405 (28.4%) Milnacipran 100 mg: 137/401 (34.2%) Milnacipran 200 mg: 144/401 (35.9%)
Selective reporting (reporting bias)	Unclear risk	Trial registration available but did not specify outcome measures ‐ just outcomes
Other bias	Low risk	No other sources of bias were identified.