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, 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).Results: Fourteen patients (mean age ± SD 42.5 ± 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 ± 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.Conclusions: Elastomeric FLU infusion for BZD detoxification is a feasible administration device to maintain adequate, constant, and tolerated FLU concentrations for reducing BZD withdrawal symptoms.
Highlights
Benzodiazepines (BZDs) constitute one of the most broadly prescribed drug classes worldwide, the frequent and often inappropriate use is a problem that remains considerably underestimated by practitioners and most regulatory agencies [1]
Another study conducted in Italy showed that 14.0% of patients visiting general practitioners were taking BZDs, with 4.7% of the total sample being long-term users (LTU), using BZDs daily for at least 12 months [6]
The different speed in the tapering of clonazepam was due to clinical criteria, in particular we considered the quality of sleep and the intensity of withdrawal symptoms
Summary
Benzodiazepines (BZDs) constitute one of the most broadly prescribed drug classes worldwide, the frequent and often inappropriate use is a problem that remains considerably underestimated by practitioners and most regulatory agencies [1]. In Italy, about 7.5–10% of adult population are BDZ users, half of these being long-term users (LTU) with a diagnosis of BZD use disorder [5]. For long-term users, in general, if properly applied, gradually reducing the dosage works, but it is much less effective for high-dose users [2, 8, 9]. This is worth mentioning because withdrawing from high doses of BZD carries significant risk for the health of the patient [2, 10]
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