Feasibility of reversing benzodiazepine tolerance with flumazenil

@article{Savic1991FeasibilityOR,
  title={Feasibility of reversing benzodiazepine tolerance with flumazenil},
  author={Ivanka Savic and Lennart Wid{\'e}n and Sharon Stone-Elander},
  journal={The Lancet},
  year={1991},
  volume={337},
  pages={133-137}
}
Effects of flumazenil in the treatment of benzodiazepine withdrawal – a double-blind pilot study
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There was an overall difference between patients and controls, with patients scoring higher on negative and somatic items and lower on positive psychological items, and flumazenil reduced symptoms thought to be important in withdrawal in patients treated for benzodiazepine dependency.
Pharmacology of flumazenil
  • J. Whitwam, R. Amrein
  • Medicine, Psychology
    Acta anaesthesiologica Scandinavica. Supplementum
  • 1995
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The existence of flumazenil is important, with implications for future research and the development of minimally invasive therapy and day‐case surgery, and with increasing pressures on non‐anaesthetically trained practitioners to perform sedation, it has important implications for safety.
Intravenous flumazenil versus oxazepam tapering in the treatment of benzodiazepine withdrawal: a randomized, placebo‐controlled study
TLDR
The effectiveness of FLU may reflect its capacity to upregulate BZD receptors and to reverse the uncoupling between the recognition sites of BzD and GABA, on the GABA A macromolecular complex, that has been reported in tolerant subjects.
Oral Flumazenil in the Treatment of Epilepsy
TLDR
No adequately designed long-term trials have been conducted on treatment of epilepsy using flumazenil, rendering evaluation of its use as a single-agent antiepileptic difficult.
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Preliminary in vitro water bath and in vivo biocompatibility data in sheep show that such an implant is feasible and so is likely to be used in clinical trials in the near future, and could be capable of managing both acute and longer term benzodiazepine withdrawal sequelae.
A pilot study of the effects of flumazenil on symptoms persisting after benzodiazepine withdrawal
TLDR
The benefits last between a few hours and several days despite flumazenil's otherwise short duration of action, however, symptoms did return to varying degrees in most cases, suggesting the need for repeated doses.
Flumazenil-precipitated withdrawal in healthy volunteers following repeated diazepam exposure
TLDR
These findings support previous human research studies indicating that flumazenil precipitates withdrawal after short chronic exposure to benzodiazepines and suggests that duration of exposure does not influence the intensity of withdrawal beyond the first week of exposure.
Benzodiazepine Receptor Antagonists
TLDR
Flumazenil represents a promising tool for pharmacological investigations of the GABAergic system and for imaging of the benzodiazepine receptor, and as a neuronal marker in epilepsy and cerebral ischaemia.
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