Amitriptyline for neuropathic pain in patients with leprosy: a bicenter randomized controlled trial.

In this bicenter, randomized, double-blind, placebo-controlled trial, we evaluated the effectiveness and safety of amitriptyline as an add-on therapy for leprosy-related neuropathic pain. A total of 117 participants were randomly assigned to receive amitriptyline or placebo for 9 weeks. The primary outcome was the change in pain intensity on a 100-mm visual analogue scale. Secondary outcomes included pain interference, responder rates, neuropathic pain symptoms, mood, sleep, catastrophizing, quality of life, and the Patient Global Impression of Change. No significant differences were observed between treatment arms for the primary end point. Patient Global Impression of Change scores were higher with amitriptyline, and no differences were detected between the other secondary outcomes. Amitriptyline was well-tolerated, and compliance was high in both arms. Treatment-emergent adverse events occurred in 81% of participants analysed in the amitriptyline arm and 94% in the placebo arm, were mostly mild or moderate, and no serious events were reported. A preplanned exploratory analysis examined the effects of therapy on pain phenotypes based on the intensity of spontaneous pain scores (burning, squeezing, and pressure pain). Participants with lower spontaneous pain scores at baseline showed lower pain severity, reduced emotional burden, and better quality-of-life outcomes compared with those with higher scores, regardless of treatment allocation. No significant differences between amitriptyline and placebo were observed within either symptom-defined phenotype. Amitriptyline did not provide superior analgesia compared with placebo when used as add-on therapy for neuropathic pain in people with leprosy. The clinical phenotypic heterogeneity of leprosy-related neuropathic pain may be relevant in future trial designs.