Khoromi 2007.

Study characteristics
Methods	Design: cross‐over Duration: 9 weeks Assessment: baseline and post‐intervention Country: USA
Participants	Pain condition: chronic lumbar root pain Population: people with lumbar radiculopathy Minimum pain intensity: ≥ 4 on 0‐10 VAS Inclusion criteria Evidence of lumbar radiculopathy, including pain in one or both buttocks or legs for ≥ 3 months for at least 5 days a week Average leg pain of at least 4/10 for the past month on a NRS of 0–10 where 0 represents no pain and 10 represents the worst possible pain Exclusion criteria Physical and mental health comorbidities Total participants randomised: 55 Age in years (median, range): 53 (19‐65) Gender: 25/55 were female Pain duration in years (median, range): 5 (0.3‐37)
Interventions	Placebo (benzotropine ≤ 1 mg) Active placebo Identical to antidepressant Dosing the same as intervention arms: ranged from 0.25‐1 mg a day Morphine ≥ 15 and ≤ 90 mg Opioid Forced titration to maximum tolerated dose Mean dose: 62 ± 29 mg/day Nortriptyline ≥ 25 and ≤ 100 mg TCA Forced titration to maximum tolerated dose Mean dose: 84 ± 24.44 mg/day Morphine ≥ 15 and ≤ 90 mg + nortriptyline ≥ 25 and ≤ 100 mg Combined intervention: opioid + TCA Forced titration to maximum tolerated doses Mean doses: morphine, 49 ± 27 mg/day plus nortriptyline, 55 mg ± 33.18 mg/day
Outcomes	Pain intensity Mood Physical function AEs Withdrawal
Missing data methods	Completer‐only analysis
Funding source	Non‐pharmaceutical: "This study was supported by an intramural grant from the National Institute of Dental and Craniofacial Research."
Conflicts of interest	NR
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were assigned by random numbers within blocks of four to 1 of 4 treatment sequences specified by a Latin square.
Allocation concealment (selection bias)	Unclear risk	Allocation procedures NR
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind, identical appearing study drugs, sham dosing
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	Completer‐only analysis. High attrition overall Attrition Total: 27/55 (49.1%) Placebo: 9/55 (16.4%) Morphine 15‐90 mg: 9/55 (16.4%) Nortriptyline 25‐100 mg: 3/55 (5.5%) Morphine 15‐90 mg + nortriptyline 25‐100 mg: 6/55 (10.9%)
Selective reporting (reporting bias)	Low risk	All outcomes registered prospectively on clinicaltrials.gov
Other bias	Low risk	No other sources of bias were identified.