{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:34:51Z","timestamp":1790386491840,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>An effective approach in the treatment of benzodiazepine (BZD) overdosing and detoxification is flumazenil (FLU). Studies in chronic users who discontinued BZD in a clinical setting suggested that multiple slow bolus infusions of FLU reduce BZD withdrawal symptoms. The aim of this study was to confirm FLU efficacy for reducing BZD withdrawal syndrome by means of continuous elastomeric infusion, correlated to drugs plasma level and patients' compliance.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Seven-day FLU 1 mg\/day subcutaneously injected through an elastomeric pump and BZDs lormetazepam, clonazepam, and lorazepam were assessed by HPLC-MS\/MS in serum of patients before and after 4 and 7 days of FLU continuous infusion treatment. Changes in withdrawal severity were assessed by using the BZD Withdrawal Scale (BWS).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Fourteen patients (mean age \u00b1 SD 42.5 \u00b1 8.0 years, 5 male and 9 female), admitted to the hospital for high-dose BZD detoxification, were enrolled in the study. Serum FLU concentrations significantly decreased from 0.54 \u00b1 0.33 ng\/ml (mean \u00b1 SD) after 4 days of treatment to 0.1 \u00b1 0.2 ng\/ml at the end of infusion. Lormetazepam concentrations were 502.5 \u00b1 610.0 ng\/ml at hospital admission, 26.2 \u00b1 26.8 ng\/ml after 4 days, and 0 at the end of treatment. BWS values decreased during FLU treatment temporal period. FLU was well-tolerated by patients.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Elastomeric FLU infusion for BZD detoxification is a feasible administration device to maintain adequate, constant, and tolerated FLU concentrations for reducing BZD withdrawal symptoms.<\/jats:p>","DOI":"10.3389\/fpsyt.2021.646038","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T04:29:55Z","timestamp":1616041795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Continuous Infusion of Flumazenil in the Management of Benzodiazepines Detoxification"],"prefix":"10.3389","volume":"12","author":[{"given":"Anna","family":"Benini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Gottardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiano","family":"Chiamulera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bertoldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Zamboni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Lugoboni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1056\/NEJMc1705239","article-title":"Treatment of benzodiazepine dependence","volume":"376","author":"Soyka","year":"2017","journal-title":"N Engl J Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2086","DOI":"10.1111\/j.1360-0443.2011.03563.x","article-title":"Benzodiazepines revisited: will we ever learn?","volume":"106","author":"Lader","year":"2011","journal-title":"Addiction."},{"key":"B3","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1097\/YIC.0b013e328105e0f2","article-title":"Benzodiazepine prescribing to the Swiss adult population: results from a national survey of community pharmacies","volume":"22","author":"Petitjean","year":"2007","journal-title":"Int Clin Psychopharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"817","DOI":"10.4088\/JCP.v63n0912","article-title":"Use of psychotropic medication in the general population of France, Germany, Italy, and the United Kingdom","volume":"63","author":"Ohayon","year":"2002","journal-title":"J Clin Psychiatry"},{"key":"B5","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s002280050063","article-title":"Use of benzodiazepines in the Italian general population. 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