1. At week 16, average neuropathic pain score decreased for all three treatment groups.
2. Pain reduction was greater in the combination therapy group compared to monotherapy.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Peripheral neuropathy is a common microvascular complication associated with diabetes and is often a significant quality-of-life burden for patients. First-line medications for neuropathic pain include amitriptyline, duloxetine, pregabalin, and gabapentin. However, little is known about their comparative efficacies and the optimal combination for symptom relief. This randomized controlled trial aimed to assess the safety and efficacy of different first-line neuropathic medications for the treatment of diabetic peripheral neuropathic pain (DPNP). More specifically, this study assessed the relative efficacies of combinations comprising of amitriptyline-pregabalin, pregabalin-amitriptyline, duloxetine-pregabalin, and each monotherapy separately. The primary outcome was mean change in daily pain during week 16 of each pathway while key secondary outcomes included daily pain score at week 6 and quality of life. According to study results, average daily pain during the final week decreased in all three pathways and was similar between treatment groups. In addition, participants who initially received monotherapy but switched to combination therapy showed significantly improved pain scores compared to those who remained on monotherapy. However, this study was limited by self-reported pain, a subjective marker that differs from patient to another.
Relevant Reading: Efficacy of Low-Dose Amitriptyline for Chronic Low Back Pain
In-depth [randomized-controlled trial]: In the OPTION-DM study, 252 patients were screened for eligibility across 13 centers in the UK between Nov 14, 2017, and Jul 29, 2019. Included were patients ≥ 18 years with known diabetes, distal symmetrical polyneuropathy, and neuropathic pain ≥ 3 months. Patients were randomly assigned to monotherapy with pregabalin, amitriptyline, or duloxetine, or one of 3 pathways: amitriptyline supplemented with pregabalin (A-P), pregabalin supplemented with amitriptyline (P-A), and duloxetine supplemented with pregabalin (D-P) for 16 weeks. At week 16, average pain score decreased from 6.6 (standard deviation [SD] 1.5) to 3.3 (SD 1.8) in all 3 pathways (intergroup difference: -0.1 D-P vs. A-P, -0.1 P-A vs. A-P, and 0.0 P-A vs. D-P) without any significant differences between combination treatment groups. Mean pain reduction was greater in the combination therapy group (1.0, SD 1.3) compared to monotherapy (0.2, SD 1.5). Majority of adverse events were mild in severity, including nausea, dizziness, and dry mouth. The P-A combination had significantly fewer discontinuations due to treatment-emergent adverse events compared to A-P and D-P (5% vs. 11% vs. 17%, respectively; p=0.031). Findings from this study suggest that all three treatment groups were comparable in efficacy although further research is needed.
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