Arnold 2010a.

Study characteristics
Methods	Design: parallel Duration: 8 weeks Assessment: baseline and post‐intervention (8 weeks) Country: USA
Participants	Pain condition: fibromyalgia Population: adults with fibromyalgia Minimum pain intensity: ≥ 40 on 0‐100 VAS Inclusion criteria People aged ≥ 18 meeting the ACR criteria for fibromyalgia (widespread pain for at least 3 months, and pain in at least 11 of 18 specific tender point sites) Score of ≥ 40 on 100 mm ViAS of the Short Form McGill Pain Questionnaire Exclusion criteria Other severe pain conditions; severe hepatic impairment; any inflammatory musculoskeletal disorder; rheumatic disease; active infection; untreated endocrine disorder; previous or current significant psychiatric disorder; severe depression (in the investigator's judgement); serious suicide risk; seizure disorder; uncontrolled narrow‐angle glaucoma; recurrent syncope or evidence of low blood pressure; symptomatic postural hypotension; significant or unstable medical or psychological conditions; pregnancy, use of an unacceptable mode of contraception, or breastfeeding; or involvement in disability claims, civil litigation, or workman's compensation claims for fibromyalgia Exclusions based on concomitant medications or treatments included tender‐point injections and use of fluoxetine or opioids within 30 days before the study; use of thioridazine or inhibitors of cytochrome P450 3A4 within 14 days before the study; use of muscle relaxants, antidepressants, anticonvulsants, oral steroids, mexiletine, dopamine agonists, long‐acting benzodiazepines, acupuncture, or TENS within 7 days before the study; and use of diphenhydramine or melatonin within 1 day before the study. Total participants randomised: 268 Age in years (mean, range): 50 (20‐84) Gender: 239/268 were female Pain duration in years (mean, range): 7 (0‐46.8)
Interventions	Esreboxetine SNRI Initial dose 2 mg/day, titrated to individual tolerability by 2 mg/day to a maximum of 8 mg/day Placebo Inert Matched appearance
Outcomes	Pain intensity Quality of life Sleep Mood Physical function Moderate pain relief Substantial pain relief PGIC AEs SAEs
Missing data methods	LOCF
Funding source	Pharmaceutical ‐ Pfizer
Conflicts of interest	Dr Arnold has received grants/research support from Allergan, Boehringer Ingelheim, Cypress Biosciences Inc., Forest Laboratories Inc., Eli Lilly and Company, Pfizer Inc., Sanofi‐Aventis, and Wyeth Pharmaceuticals. She has been a consultant for Allergan, AstraZeneca, Boehringer Ingelheim, Cypress Biosciences, Forest Laboratories, Eli Lilly and Company, Organon, Pfizer, sanofi‐aventis, Sepracor, Takeda, Theravance, Inc., DCB, Vivus, Inc., and Wyeth. She has served on speakers' bureaus for Forest Laboratories, Eli Lilly and Company, and Pfizer. Drs Chatamra, Hirsch, and Stoker were employees of Pfizer at the time of the study. They have indicated that they have no other conflicts of interest with regard to the content of this article.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Allocation to treatment groups was performed according to a computer‐generated randomisation code.
Allocation concealment (selection bias)	Low risk	Allocation was managed through a centralised telerandomisation system.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Placebo matched appearance and dose
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	Equal attrition (20%), LOCF supplemented by BOCF Attrition: Total: 55/267 (20.5%) Placebo: 27/133 (20.3%) Esreboxetine: 27/134 (20.1%)
Selective reporting (reporting bias)	Unclear risk	Some changes in what were secondary or primary outcomes, not 100% lining up with protocol but primary outcome remains the same
Other bias	Low risk	No other sources of bias were identified.