A meta-epidemiological study on the reported treatment effect of pregabalin in neuropathic pain trials over time.

backgroundPregabalin is a drug used to treat neuropathic pain, and its use has increased substantially since 2007. Early trials found a strong treatment effect on pain for post-herpetic neuralgia and diabetic neuropathy. However more recent studies have failed to replicate these results.

methodsThis meta-epidemiological study aimed to assess change in the reported effectiveness of pregabalin in neuropathic pain trials over time, and if a change is present, determine any associated factors. DATA SOURCES: We performed electronic searches for published trials in Medline, Embase and Cochrane Central Register of Controlled Trials databases; and unpublished trials on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australia New Zealand Clinical Trials Registry with no restrictions. STUDY SELECTION: We included randomized, placebo-controlled trials of pregabalin for treatment of neuropathic pain in adults. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted study data: sample size and mean baseline, end-point and change in pain scores with measures of variance, trial end year, publication year, clinical indication, funding source, country of study, treatment duration, treatment dose, mean age and percentage male. PRIMARY OUTCOME MEASURE: We defined treatment effect as the mean difference in pain scores between pregabalin and placebo groups at trial end-point and assessed for change over time using a random-effects meta-regression, adjusted for sample size, indication, treatment duration (weeks) and treatment dose.

resultsWe included 38 randomized published trials (9038 participants) and found that between 2003 and 2020, the reported treatment effect of pregabalin decreased by 0.4 points (95% CI: 0.3 to 0.6; p<0.001) on an 11-point pain scale per 5-year interval, from 1.3 points (95% CI: 1.0 to 1.5) in trials conducted in 2001-2005, to 0.3 (95% CI: -0.1 to 0.7) in trials conducted in 2016-2020. The reported treatment effect was lower than the minimal clinically important difference (MCID) of 1.7 points across all time periods, doses and most indications and was not found to be associated with study characteristics.

conclusionsThe reported treatment effect or analgesic efficacy of pregabalin from clinical trials has diminished over time. Clinical recommendations may need to be re-evaluated to account for recent evidence and to consider whether pregabalin therapy is indicated.