The Effect of Bupropion in Peripheral Neuropathic Pain A Randomized, Double‐Blind, Placebo‐Controlled Study

BACKGROUND: Monoamine reuptake inhibitors are evidenced first-line treatments of peripheral neuropathic pain. The aim was to investigate if bupropion, a drug that specifically inhibits neuronal noradrenaline and dopamine reuptake, relieves neuropathic pain and if a potential effect depends on status of conditioned pain modulation (CPM) and sensory phenotype (irritable vs. non-irritable nociceptor). METHOD: Study design was randomized, double-blind, placebo-controlled, and cross-over. Patients with peripheral neuropathic pain were treated with bupropion and placebo in a random order, with treatment periods lasting 6 weeks preceded by a 1-week baseline. Change in daily average pain was the primary outcome. Other outcomes included pain relief and 30% and 50% pain reduction. RESULTS: 67 patients were randomized and included in the analysis. The mean daily average pain changed from NRS 6.4 to 5.5 after bupropion treatment with an average effect as compared with placebo of -0.5 (95% CI -0.8 to -0.1, p = 0.005). No relation was found between response to treatment and efficiency of CPM or sensory phenotype. There was no significant effect on the pain relief scale. A 30% and 50% pain reduction was found in 10 and 6 patients respectively with a NNT for 50% pain reduction of 15. Bupropion was well tolerated. CONCLUSION: Bupropion had a pain-relieving effect independent of CPM efficiency and sensory phenotype. NNT for 50% pain reduction was higher than reported for first-line treatments, but bupropion treatment may still be an option in patients with insufficient response or intolerable side effects on such treatments. SIGNIFICANCE STATEMENT: This study finds a modest pain-relieving effect of bupropion on peripheral neuropathic pain independent of function of conditioned pain modulation. Bupropion could be an alternative treatment for patients with a lack of effect or intolerable side effects to first-choice treatments of peripheral neuropathic pain. Further, larger studies are needed to determine optimal dosage. TRIAL REGISTRATION: The study is registered with the EU clinical trials Register (EudraCT 2019-000243-27) on March 15th 2019. The study is approved by the Ethical Committee of the Region of Southern Denmark (also included approval for Regions of Central Denmark; no. S-20190010) and the Danish Medicine Agency (no. 2019012986) and is registered with the Danish Data Protection Agency (via the Region of Southern Denmark's internal notification; no. 19/17111).