Comparative Effectiveness of Pregabalin With Duloxetine Versus Pregabalin With Amitriptyline in Chronic Low Back Pain...

Chronic low back pain (CLBP) with radiculopathy is a disabling, predominantly neuropathic condition that imposes a heavy burden in low- and middle-income countries (LMICs). Combination pharmacotherapy targeting multiple pain pathways is increasingly used, yet head-to-head comparisons specifically in radicular CLBP are scarce. This prospective study compared pregabalin combined with duloxetine versus pregabalin combined with amitriptyline for pain reduction and functional improvement.

This study was conducted between July 2024 and December 2025, during which 76 adults with clinically diagnosed CLBP and radiculopathy were enrolled at Dhaka Medical College Hospital, Bangladesh. Patients were assigned non-randomly, in the order of enrollment, to Group I (pregabalin with duloxetine) or Group II (pregabalin with amitriptyline), with 38 patients in each group. Pain and disability were assessed using the Numeric Pain Rating Scale (NPRS) and the Oswestry Disability Index (ODI) at baseline and at 4, 8, 12, and 24 weeks. Analyses used t tests, Mann-Whitney U tests, baseline-adjusted ANCOVA, responder analyses, and linear mixed-effects models, reporting effect sizes and 95% confidence intervals.

Both groups improved substantially over time. However, the groups were markedly imbalanced at baseline (NPRS and ODI, both p < 0.001; standardized mean difference ≈0.9); the baseline-adjusted ANCOVA was therefore the primary analysis, and after adjustment for baseline severity the between-group differences were no longer statistically significant for either NPRS or ODI (all ANCOVA p > 0.40). In unadjusted, secondary analyses the crude reductions were larger with duloxetine (Week-24 NPRS between-group difference -1.54, 95% CI -2.72 to -0.37, Cohen's d = 0.60; ≥ 50% pain reduction 60.5% [23/38] vs. 34.2% [13/38], p = 0.04), but these crude comparisons are confounded by the baseline imbalance and are regarded as exploratory. Sedation (7.9% [3/38] vs. 31.6% [12/38], p = 0.02) and drowsiness (13.2% [5/38] vs. 39.5% [15/38], p = 0.02) were less frequent with duloxetine, although adverse-event ascertainment was open-label and incomplete.

In this non-randomized cohort, the pregabalin-duloxetine combination was associated with greater crude improvement, and duloxetine-treated participants reported fewer episodes of sedation and drowsiness; however, the apparent efficacy advantage was substantially attenuated after accounting for baseline imbalance, and because adverse-event ascertainment was open-label and incomplete, the tolerability signal also remains exploratory. These findings should be regarded as hypothesis-generating and require confirmation in adequately powered randomized trials.