Non-opioid antinociceptive drugs : risk of respiratory depression and death related to concomitant use of gabapentinoids in addition to opioids

IntroductionRespiratory depression and opioid-related death are reported when opioids are associated with gabapentinoids. Meta-analyses of randomized clinical trials investigating efficacy and safety of such association failed to assess these risks because of the lack of data. The aim of this systematic review was to investigate the risk of respiratory depression or death during this combination in the scientific literature, including case reports or series, observational studies, and clinical trials.Areas coveredPubMed (R), Web of Science (R), Embase (R), and Google Scholar (R) were searched from their inception to December 2021, for original articles in English, French, and German. Data synthesis was done on a narrative approach by type of articles.Expert opinionThe review included 25 articles (4 case reports, 2 cross-sectional, 3 case-control, 14 cohort studies, and 2 clinical trials). Respiratory depression or opioid-related death and co-exposure to gabapentinoids were associated in perioperative setting/chronic pain (odds ratios around 1.3) and in opioid maintenance treatment (hazard ratio 3.4). These findings are in agreement with experimental studies showing that a single dose of gabapentinoid may reverse opioid respiratory tolerance. Because the combination gabapentinoids-opioids is highly prevalent in all clinical context, all health care professionals and patients must be aware of this risk.