Risk of gastrointestinal bleeding with gabapentin versus duloxetine in older adults with neuropathic pain: a target trial emulation cohort study.

Risk of gastrointestinal bleeding with gabapentin versus duloxetine in older adults with neuropathic pain: a target trial emulation cohort study.

Publication date: Aug 09, 2026

Gabapentin and duloxetine are common treatments for neuropathic pain in adults over 65, but data on their gastrointestinal (GI) bleeding risk are limited. We compared GI bleeding risk after starting gabapentin or duloxetine in this population. We used the TriNetX US Collaborative Network to conduct an active-comparator cohort study using target trial emulation. Patients aged 65 years and above with neuropathic pain diagnosed between January 2020 and December 2024 were included, excluding those with prior GI bleeding, major depressive disorder, or thrombocytopenia. Propensity score matching balanced key covariates. The main outcome was GI bleeding within 24 months, analyzed with Cox regression; secondary analyses included upper/lower GI bleeding, mortality, and hospitalization. Negative controls assessed confounding. The study analyzed 62,926 patients (55,236 gabapentin; 7,690 duloxetine) and matched 7,599 pairs. GI bleeding was less common with gabapentin initiators (1. 22%) than duloxetine initiators (2. 49%), showing an absolute risk reduction of 1. 27% (HR 0. 86, 95% CI 0. 84-0. 89, p 

Concepts Keywords
24months Duloxetine
Adults Gabapentin
December Gastrointestinal bleeding
Pharmacol Neuropathic pain
Thrombocytopenia Older adults

Semantics

Type Source Name
drug DRUGBANK Gabapentin
drug DRUGBANK Duloxetine
disease MESH neuropathic pain
disease MESH bleeding
disease MESH included
disease MESH major depressive disorder
disease MESH thrombocytopenia

Original Article

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