Combination Therapy for Neuropathic Pain. A Systematic Review

Pharmacological treatment is poorly effective for neuropathic pain (NP). A progressive decrease in the estimated effect of NP drugs has been reported, giving rise to an increase in multimodal analgesic approach. We performed a systematic review to assess whether there is more and better-quality evidence available since the last review. We evaluated the efficacy, tolerability and safety of double-blind randomized controlled trials involving only adult participants comparing combination therapy (CT: ≥ 2 drugs) to placebo and/or at least one other comparator with NP indication. The primary outcome was the proportion of participants reporting ≥ 50% pain reduction from baseline. Secondary outcome was the proportion of drop-outs due to treatment-emergent-adverse-events. After removing duplicates, 2323 citations were screened. 164 articles were assessed for eligibility, from which 16 were included for qualitative analysis. From the latter, only 5 lasted for at least 12 weeks and only 6 complied with required data for complete analysis, but not for meta-analysis. CT has been adopted for years without robust evidence. Efforts to achieve better quality evidence have not improved over the years. In this regard, guidelines for NP should attempt to make recommendations on CT research, prioritizing which combinations to analyze.