Gabapentinoids and Neuropathic Pain: Evaluation of the Quality of Randomised Controlled Trials: An Umbrella Review

Neuropathic pain remains a complex condition to manage. While current literature provides best practice guidelines for the use of gabapentinoids in this indication, these recommendations are primarily based on randomised clinical trials (RCTs) and meta-analyses of varying methodological quality. To support evidence-based prescribing, we conducted an evaluation of the overall confidence in meta-analytic findings on the efficacy of gabapentinoid in adults. A systematic review of the meta-analyses of RCTs retrieved from the MEDLINE (PubMed) database was performed. The methodological quality of these meta-analyses was assessed using the AMSTAR 2 tool (A MeaSurement Tool to Assess systematic Reviews) and compared when available with the quality of evidence determined by the GRADE approach. Among the 16 included meta-analyses, 14 were rated as having 'critically low' quality, one as 'low' and one as 'moderate' according to AMSTAR 2. GRADE and AMSTAR 2 assessments were both available for six meta-analyses, but only one yielded a concordant result. According to AMSTAR 2, the highest-quality meta-analysis was the one published in the Cochrane Database of Systematic Reviews and concluded that more participants had substantial benefit (at least 50% pain relief or patient global impression change very much improved) with gabapentin at 1200 mg daily or greater than with placebo (in postherpetic neuralgia: RR = 1.8 [95% CI 1.5 to 2.1] and in painful diabetic neuropathy: RR = 1.9 [95% CI 1.5 to 2.3]). One limitation of this work is the inconsistent use of the term neuropathic pain, which may be defined differently across studies.