Arnold 2010b.

Study characteristics
Methods	Design: parallel Duration: 12 weeks Assessment: baseline and post‐intervention (12 weeks) Country: USA and Canada
Participants	Pain condition: fibromyalgia Population: adults with fibromyalgia Minimum pain intensity: ≥ 40 on 0‐100 VAS Inclusion criteria People aged 18‐70 who met the ACR 1990 criteria for fibromyalgia Patients were required to have a raw score of 4 on the physical function domain of the Fibromyalgia Impact Questionnaire at screening and a mean VAS pain score of between 40 and 90 on the electronic patient experience diary 24‐hour recall pain report (0‐100 VAS) during the 14‐day baseline period Exclusion criteria Other rheumatic or medical conditions that displayed symptoms similar to fibromyalgia; previous exposure to milnacipran; treatment with an investigational drug within 30 days of screening; BDI score > 25 at screening or baseline; current major depressive episode as determined by the MINI; significant risk of suicide according to the investigator’s judgement or the results of the MINI or the BDI; lifetime history of psychosis, hypomania, or mania, substance abuse; other severe psychiatric illness as determined by investigator judgement; history of behaviour that would, in the investigator’s judgement, prohibit compliance for the duration of the study; active or pending disability claim; worker’s compensation claim, or litigation; pregnancy or breastfeeding; unacceptable contraception method; active or unstable medical illness Concomitant treatments considered to be criteria for exclusion included digitalis; centrally acting medications for fibromyalgia; TENS; biofeedback; tender and trigger point injections; acupuncture; and anaesthetic or narcotic patches Total participants randomised: 1025 Age in years (mean, SD): NR Gender: 977/1025 were female Pain duration in years (mean): 10.8
Interventions	Milnacipran n = 516 SNRI 100 mg/day, forced titration over 6 weeks Placebo n = 509 Inert Matched appearance and dosing schedule
Outcomes	Pain intensity Physical function Mood Quality of life Moderate pain relief Substantial pain relief PGIC AEs SAEs Withdrawal
Missing data methods	BOCF
Funding source	Pharmaceutical ‐ Forest Laboratories
Conflicts of interest	Dr Arnold has received consulting fees, speaking fees, and/or honoraria from Cypress Bioscience, Wyeth, Boehringer Ingelheim, Allergan, Takeda, UCB, Theravance, AstraZeneca, and Sanofi‐Aventis (less than USD 10,000 each) and from Eli Lilly, Pfizer, and Forest Laboratories (> USD 10,000 each) and has received research support from Eli Lilly, Cypress Bioscience, Wyeth, Boehringer In‐gelheim, Allergan, Forest Laboratories, and Pfizer. Drs R. M. Gendreau and J. F. Gendreau own stock or stock options in Cypress Bioscience. Drs Palmer and Wang own stock or stock options in Forest Laboratories.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation assignment by computer code in blocks of 4
Allocation concealment (selection bias)	Low risk	Assignment to treatment groups was conducted centrally (i.e. at the study level) using an interactive voice response system.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Identical placebo appearance and matched dosing schedule
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Self‐reported outcomes from blinded participants
Incomplete outcome data (attrition bias) All outcomes	Low risk	Similar attrition across both arms, BOCF used for imputation Attrition: Total: 309/1025 (30.1%) Placebo: 150/509 (29.5%) Milnacipran 100 mg: 159/516 (30.8%)
Selective reporting (reporting bias)	Low risk	Trial registered prospectively on clinicaltrials.gov
Other bias	Low risk	No other sources of bias were identified.