Drug combinations in the treatment of neuropathic pain

Pharmacotherapy, the main treatment option for neuropathic pain, remains a major clinical challenge. The most commonly studied drug classes in the context of neuropathic pain-antidepressants, anticonvulsants, and opioids-have only limited efficacy and frequent dose-limiting adverse effects. Yet, most guidelines recommend monotherapy as the first line of neuropathic pain treatment. Recent understanding of neuropathic pain pathophysiology suggests that multiple mechanisms, both at the peripheral and the central nervous system levels, underlie neuropathic pain, pointing to the possibility that targeting multiple mechanisms simultaneously can improve treatment outcome. A few clinical trials using various drug combinations for neuropathic pain have already been published but yielded inconsistent results, partially due to methodological problems associated with the conduction of such trials. Nonetheless, combination therapy remains an intriguing treatment option for neuropathic pain, awaiting future high-quality validating trials.