Sindrup 2003.

Methods	Double‐blind, placebo‐controlled cross‐over design with 3 x 4‐week periods and 1‐week washout
Participants	40 participants with painful polyneuropathy of at least 6 months' duration. Mean age 56 years (range 31‐69 years). 23 men and 9 women were included in the data analysis. Participants were recruited in 2 Danish hospitals
Interventions	Venlafaxine 75 mg/day in week 1, 150 mg/day in week 2, 225 mg/day in weeks 3 and 4, imipramine 50 mg/day in week 1, 100 mg/day in week 2, 150 mg/day in weeks 3 and 4 vs. placebo for 5 weeks
Outcomes	Participant‐reported daily rating of 4 aspects of pain were summed (pain paroxysms, constant pain, touch, and pressure‐evoked pain ‐ all on 11‐point VAS). Patient's global impression of pain relief (complete, good, moderate, slight, none). Adverse effects and use of escape medication Complete/good pain relief: 9/29 imipramine; 2/29 placebo; 7/30 venlafaxine. Complete/good/moderate pain relief: 14/29 imipramine; 2/29 placebo; 8/30 venlafaxine. Authors report NNTB of 5.2 for at least moderate pain relief with venlafaxine, but did not provide raw data or confidence intervals. Use of escape medication (paracetamol) not significantly different
Notes	1‐week baseline observations. People with diabetes (15 participants) more likely to gain clinically relevant pain relief than people without diabetes (17 participants). 33/40 participants completed all 3 arms of study. 7 withdrew due to adverse effects (1 imipramine; 2 placebo; 4 venlafaxine). 1 lost to follow‐up
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Authors stated that 'assignment to one of six possible treatment sequences was random via a computer‐generated randomization code' and that this 'randomization plan was generated by one author who was not involved in the conduct of the trial'
Allocation concealment (selection bias)	Low risk	Participants were numbered consecutively. Sealed envelopes were employed
Blinding of participants and personnel (performance bias) All outcomes	Low risk	'Double dummy technique was employed as venlafaxine, and its corresponding placebo capsules had a different appearance than imipramine and its corresponding placebo tablets'
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The randomisation plan was generated by an author who was not involved in the conduct of the trial and double‐blinding was maintained throughout
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	> 10% of participants did not complete the trial. Last observation carried forward analysis was employed
Size	High risk	< 50 participants per treatment arm