Lipone 2020.

Study characteristics
Methods	Design: parallel Duration: 8 weeks Assessment: baseline and post‐intervention Country: Czech Republic, Hungary, and Poland
Participants	Pain condition: painful diabetic neuropathy Population: people with painful diabetic neuropathy Minimum pain intensity: ≥ 4 on 0‐10 scale Inclusion criteria Aged 18‐75 painful diabetic neuropathy manifesting with distally distributed neuropathic pain ≥ 4 on 0‐10 pain intensity scale Exclusion criteria Other pain conditions, general physical conditions (glaucoma, hisotry of seizures, etc), and significant mental disorders Total participants randomised: 142 Age in years (mean): 62.7 Gender: 68/142 were female Pain duration in years (mean, SD): NR
Interventions	Placebo + gabapentin 2400 mg n = 48 Placebo + anticonvulsant Gabapentin open‐label, placebo identical to trazodone Trazodone 30 mg + gabapentin 2400 mg n = 43 Combined intervention: SARI antidepressant + anticonvulsant Fixed dose Gabapentin in open‐label condition Trazodone 60 mg + gabapentin 2400 mg n = 51 Combined intervention: SARI antidepressant + anticonvulsant Fixed dose Gabapentin in open‐label condition
Outcomes	Pain intensity Substantial pain relief AEs SAEs Withdrawal
Missing data methods	ITT with LOCF
Funding source	Pharmaceutical: "This study was sponsored by Angelini Pharma S.p.A. (S. Palomba, Pomezia, Rome, Italy)."
Conflicts of interest	Giorgio Cruccu received personal fees for advisory boards or consultancy from Angelini, Grunenthal, and Lilly, and personal fees for educational activity by PTS Global Services. Andrea Truini received honoraria for speaking at symposia or research financial supports from Alpha‐Sigma, Angelini Pharma, Epitech, FB Health, Pfizer, and Grunenthal. Edvard Ehler has no conflicts of interest that are directly relevant to the content of this study; however, his institution received a fee for conducting the clinical trial from Angelini Pharma S.p.A. Marcin Nastaj and Ilona Palka‐Kisielowska received principal investigator fees from Angelini Pharma S.p.A. Fabrizio Calisti, Agnese Cattaneo, Alessandro Comandini, Alessandra Del Vecchio, Giorgio Di Loreto, Paola Lipone, and Ilena Pochiero are full‐time employees of Angelini Pharma S.p.A.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were randomised in a 1:1:1 ratio to the 3 parallel groups, based on a computer‐generated sequence
Allocation concealment (selection bias)	Unclear risk	Allocation procedures NR
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Double‐blinding was maintained throughout all treatment periods by using a TRZ [trazodone] solution matching PLB [placebo] solution and the same dosing regimen for all groups in terms of timing and number of drops."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Self‐reported outcomes by blinded participants
Incomplete outcome data (attrition bias) All outcomes	High risk	ITT with LOCF Attrition Total: 38/142 (26.8%) Gabapentin 2400 mg: 13/48 (27.1%) Trazodone 30 mg + gabapentin 2400 mg: 10/43 (23.3%) Trazodone 60 mg + gabapentin 2400 mg: 15/51 (29.4%)
Selective reporting (reporting bias)	Unclear risk	Do not report a lot of the secondary outcomes clearly, the baseline or the post‐intervention, these are also NR in the trial registry
Other bias	Low risk	No other sources of bias were identified.