AUTHOR=Benini Anna , Gottardo Rossella , Chiamulera Cristiano , Bertoldi Anna , Zamboni Lorenzo , Lugoboni Fabio TITLE=Continuous Infusion of Flumazenil in the Management of Benzodiazepines Detoxification JOURNAL=Frontiers in Psychiatry VOLUME=Volume 12 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.646038 DOI=10.3389/fpsyt.2021.646038 ISSN=1664-0640 ABSTRACT=Abstract 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. Methods Seven-day FLU 1 mg/day subcutaneously injected through an elastomeric pump and BZDs lormetazepam, clonazepam, lorazepam were assessed by HPLS-MS/MS in serum of patients before, after 4 and 7 days of FLU continuous infusion treatment. Changes in withdrawal severity were assessed by using the BZD Withdrawal Scale (BWS). Results Fourteen patients (mean age ± SD 42.5 ± 8.0 yrs, 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 ± 0.33 ng/ml (mean ± SD) after 4 days of treatment to 0.1 ± 0.2 ng/ml at the end of infusion. Lormetazepam concentrations were 502.5 ± 610.0 ng/ml at hospital admission, 26.2 ± 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.