ReviewBritish journal of clinical pharmacology2014
Benzodiazepine dependence and its treatment with low dose flumazenil.
Review in British journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 157 citations in OpenAlex.
- Flumazenil versus placebo or no intervention for people with cirrhosis and hepatic encephalopathy.The Cochrane database of systematic reviews · 2017Pooled it
- Flumazenil versus placebo or no intervention for people with cirrhosis and hepatic encephalopathy.The Cochrane database of systematic reviews · 2017Pooled it
- Synaptic correlates of benzodiazepine tolerance.Molecular psychiatry · 2026Review
- Utilization of adjunctive anti-seizure medications to facilitate chronic benzodiazepine discontinuation.The mental health clinician · 2026Review
- Anxiolytic and Memory Protective Effects of Withanolide D Isolated From Acnistus arborescens in Adult Zebrafish.Chemistry & biodiversity · 2026Article
- Deprescribing: Reducing Harm, Enhancing Care.Rambam Maimonides medical journal · 2026Review
- General practitioner-pharmacist collaboration to enhance deprescribing of psychotropics, sedatives, and anticholinergics among older polypharmacy patients in primary care: study protocol of a cluster-randomized controlled trial (PARTNER).Therapeutic advances in drug safety · 2026Article
- Comprehensive Evaluation of Methanolic Fruits Extract of Jatropha gossypifolia L.: Neuropharmacological, Cytotoxic, Anthelmintic, GC-MS Profiling, and Molecular Docking Studies.Pharmacology research & perspectives · 2025Article
- Facilitators and barriers to the deprescribing of benzodiazepines and Z-drug hypnotics in patients under 65 on adult mental health wards.Scientific reports · 2025Article
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- Article
- Medical Professionals and Pharmacological Intervention for the Treatment of Insomnia: A Cross-Sectional Study.Sleep science (Sao Paulo, Brazil) · 2025Article
- Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Long-term neurological consequences following benzodiazepine exposure: A scoping review.PloS one · 2025Article
- Risk Characterization in Patients Using Benzodiazepines While Providing Pharmaceutical Care Dispensing Service.Pharmacy (Basel, Switzerland) · 2024Article
- Article
- Current Therapeutic Strategies for the Management of Benzodiazepine (BZD) Withdrawal Syndrome: A Review.Current topics in medicinal chemistry · 2024Review
- Comparison of Remimazolam-Flumazenil versus Propofol for Recovery from General Anesthesia: A Systematic Review and Meta-Analysis.Journal of clinical medicine · 2023Review
- Switching to lemborexant for the management of insomnia in mental disorders: the SLIM study.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2023Article
- Antidotes in Clinical Toxicology-Critical Review.Toxics · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Globally benzodiazepines remain one of the most prescribed medication groups, especially in the primary care setting. With such high levels of prescribing it is not surprising that benzodiazepine dependence is common, cutting across all socioeconomic levels. Despite recognition of the potential for the development of iatrogenic dependence and the lack of any effective treatment, benzodiazepines continue to be widely prescribed in general practice. Conventional dependence management, benzodiazepine tapering, is commonly a protracted process over several weeks or months. It is often associated with significant withdrawal symptoms and craving leading to patient drop out and return to use. Accordingly, there is a worldwide need to find effective pharmacotherapeutic interventions for benzodiazepine dependence. One drug of increasing interest is the GABAA benzodiazepine receptor antagonist/partial agonist, flumazenil. Multiple bolus intravenous infusions of low dose flumazenil used either with or without benzodiazepine tapering can reduce withdrawal sequelae, and/or longer term symptoms in the months following withdrawal. Preliminary data suggest that continuous intravenous or subcutaneous flumazenil infusion for 4 days significantly reduces acute benzodiazepine withdrawal sequelae. The subcutaneous infusion was shown to be tissue compatible so the development of a longer acting (i.e. several weeks) depot flumazenil formulation has been explored. This could be capable of managing both acute and longer term benzodiazepine withdrawal sequelae. 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.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.