Gilron 2015.

Study characteristics
Methods	Design: cross‐over Duration: 6 weeks Assessment: baseline to post‐intervention Country: Canada
Participants	Pain condition: any chronic neuropathic pain Population: adults with chronic peripheral neuropathic pain Minimum pain intensity: ≥ 4 on 0‐10 VAS Inclusion criteria Peripheral neuropathy for at least 6 months ≥ 4 on 0‐10 pain intensity VAS Exclusion criteria Physical or mental health comorbidities Total participants randomised: 52 Age in years (median, range): 66 (49‐80) Gender: 14/52 were female Pain duration in years (mean, SD): 6.1 (6.4)
Interventions	Morphine ≤ 100 mg n = 52 Analgesic Flexible dosing dependent on tolerability Mean dose: 65.4 mg/day Nortriptyline n = 52 TCA Flexible dosing dependent on tolerability Mean dose: 83.9 mg/day Nortriptyline and morphine n = 52 Combined intervention: TCA and analgesic Flexible dosing dependent on tolerability Mean dose: 60.2 mg/day
Outcomes	Pain intensity Mood Sleep Moderate pain relief Substantial pain relief Withdrawal
Missing data methods	NR
Funding source	Part funded by pharmaceutical: "This work was supported by CIHR (Canadian Institutes of Health Research) Grant #MCT‐94187 and a CIHR‐Pfizer Rx&D Collaborative Research Investigator Program (CIHR Grant #MSH‐55041)."
Conflicts of interest	I. Gilron has received support from Adynxx, TARIS Biomedical, AstraZeneca, Pfizer, and Johnson & Johnson and has received grants from the Canadian Institutes of Health Research, Physicians' Services Incorporated Foundation, and Queen's University. R. R. Holden has received research funding from the Canadian Institutes of Health Research, the Social Sciences and Humanities Research Council of Canada, the American Foundation for Suicide Prevention, and Queen's University. A. C. Jackson has received grants from the Canadian Institutes of Health Research, Research Manitoba (formerly the Manitoba Health Research Council), and the University of Manitoba. The remaining authors have no conflicts of interest to declare.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomised using computer randomisation of the 3 sequences in blocks of 3.
Allocation concealment (selection bias)	Low risk	A trial pharmacist prepared a concealed allocation schedule, and the pharmacist had no further involvement in the trial. Patients were assigned in turn to the next consecutive number, and the corresponding series of study drugs was dispensed.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind, double‐dummy design
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	Unequal attrition across arms, states ITT but no imputation methods specified Attrition Total: 16/52 (30.8%) Morphine: 9/52 (17.3%) Nortriptyline ≤ 100 mg: 2/52 (3.9%) Nortriptyline + morphine: 7/52 (13.5%)
Selective reporting (reporting bias)	Low risk	All outcomes prospectively reported on ISRCTN.com
Other bias	Low risk	No other sources of bias were identified