PMID- 36662848 OWN - NLM STAT- MEDLINE DCOM- 20230125 LR - 20231118 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 18 IP - 1 DP - 2023 TI - A meta-epidemiological study on the reported treatment effect of pregabalin in neuropathic pain trials over time. PG - e0280593 LID - 10.1371/journal.pone.0280593 [doi] LID - e0280593 AB - BACKGROUND: Pregabalin 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. METHODS: This 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searches for published trials in Medline, Embase and Cochrane Central Register of Controlled Trials databases; and unpublished trials on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australia New Zealand Clinical Trials Registry with no restrictions.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. RESULTS: We 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. CONCLUSIONS: The 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. CI - Copyright: (c) 2023 Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Cheng, Emma T L AU - Cheng ETL AUID- ORCID: 0000-0002-6907-7781 AD - Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia. AD - South West Clinical Campuses, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. FAU - Cheik-Hussein, Mohammad AU - Cheik-Hussein M AD - Department of Orthopaedic Surgery, Liverpool Hospital, Liverpool, New South Wales, Australia. FAU - Lin, Noelle AU - Lin N AD - Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia. AD - South West Clinical Campuses, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. FAU - Lewin, Adriane M AU - Lewin AM AUID- ORCID: 0000-0001-6258-3692 AD - Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia. AD - South West Clinical Campuses, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. FAU - McAuley, James H AU - McAuley JH AD - School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Randwick, New South Wales, Australia. AD - NeuRA-Neuroscience Research Australia, Randwick, New South Wales, Australia. FAU - Harris, Ian A AU - Harris IA AUID- ORCID: 0000-0003-0887-7627 AD - Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, Liverpool, New South Wales, Australia. AD - South West Clinical Campuses, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. AD - Department of Orthopaedic Surgery, Liverpool Hospital, Liverpool, New South Wales, Australia. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20230120 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Analgesics) RN - 55JG375S6M (Pregabalin) SB - IM MH - Adult MH - Humans MH - Male MH - Analgesics/therapeutic use MH - *Diabetic Neuropathies/drug therapy/epidemiology MH - *Neuralgia/drug therapy/epidemiology MH - *Neuralgia, Postherpetic/drug therapy/epidemiology MH - Pregabalin/therapeutic use MH - Randomized Controlled Trials as Topic PMC - PMC9858874 COIS- The authors have declared that no competing interests exist. EDAT- 2023/01/21 06:00 MHDA- 2023/01/25 06:00 PMCR- 2023/01/20 CRDT- 2023/01/20 14:04 PHST- 2022/10/19 00:00 [received] PHST- 2023/01/03 00:00 [accepted] PHST- 2023/01/20 14:04 [entrez] PHST- 2023/01/21 06:00 [pubmed] PHST- 2023/01/25 06:00 [medline] PHST- 2023/01/20 00:00 [pmc-release] AID - PONE-D-22-28179 [pii] AID - 10.1371/journal.pone.0280593 [doi] PST - epublish SO - PLoS One. 2023 Jan 20;18(1):e0280593. doi: 10.1371/journal.pone.0280593. eCollection 2023.