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.