Combination therapy for neuropathic pain: a review of current evidence

Neuropathic pain is a debilitating chronic condition that remains very difficult to treat. Recently, a number of clinical studies have compared the effectiveness of combination drug therapy with monotherapy for neuropathic pain treatment. In this article, we summarize up-to-date clinical studies of combination therapy for the treatment of both cancer- and non-cancer-related neuropathic pain. Despite a relatively small number of clinical studies on this topic, several positive indications have emerged. First, clinical studies using gabapentin (five positive trials) and pregabalin (five positive trials and one negative trial) in combination with an opioid, cyclo-oxygenase-2 inhibitor or antidepressant have shown positive responses greater than the respective monotherapies for pain related to diabetic neuropathy and postherpetic neuropathy. Second, high-concentration (8%) topical capsaicin and a 5% lidocaine patch seem to be effective add-on therapies (a modality of combination therapy) for various neuropathic pain conditions. Third, combination therapy for cancer-related neuropathic pain has yielded only limited success based on a number of small-scale clinical studies. While there are benefits of using combination therapy for neuropathic pain treatment, including better pain relief and reduced adverse effects, more clinical studies are required in order to (i) make head-to-head comparisons between combination and single-drug therapies, (ii) identify symptom-specific combination therapies for distinctive clinical neuropathic pain conditions, (iii) explore combination therapies that include non-drug modalities such as physical therapy, psychological coping and biofeedback to facilitate functional restoration and (iv) develop new and objective evaluation tools for clinical outcome assessment.