A randomized, double-blind study of alpidem vs placebo in the prevention and treatment of benzodiazepine withdrawal syndrome

Cassano, Gb; Petracca, A.; Borghi, C.; Chiroli, Silvia; Didoni, Guido; Garreau, M.

doi:10.1016/0924-9338(96)84786-9

Cited by 7 publications

(3 citation statements)

References 24 publications

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“…Further randomized, double-blind, placebo-controlled studies are necessary to increase the knowledge to support the use of AC for the treatment of BD and BWS. [19,20]; β-blocker propranolol [21,22]; α2-agonist clonidine [23]; 5-HT 1A partial agonist buspirone [19,20,24]; anxiolytic alpidem [25]; neuroactive steroid progesterone [26]; 5-HT 3 antagonist odansetrone [27]; and BZD partial agonist flumazenil [28,29].…”

Section: Resultsmentioning

confidence: 99%

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2014

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Section: Resultsmentioning

confidence: 99%

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2014

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“…Pregabalin has demonstrated to be effective in the treatment of BD and BWS, exerting its beneficial action by reducing the severity of withdrawal and anxiety symptoms. [19,20]; β-blocker propranolol [21,22]; α2-agonist clonidine [23]; 5-HT 1A partial agonist buspirone [19,20,24]; anxiolytic alpidem [25]; neuroactive steroid progesterone [26]; 5-HT 3 antagonist odansetrone [27]; and BZD partial agonist flumazenil [28,29].…”

Section: Resultsmentioning

confidence: 99%

Anticonvulsant Agents for the Management of Benzodiazepine Dependence

Marín-Mayor¹,

López‐Muñoz²,

Rubio³

2014

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IntroductionChronic use of Benzodiazepines (BZDs) can lead to tolerance and dependence, as indicated by a BZD Withdrawal Syndrome (BWS). In general, it is preferred a gradual than an abrupt tapering of BZDs as a first step in the treatment of BZD Dependence (BD). In addition, a great variety of agents have been used as adjuvant medication for BD. Recently, research has focused in the use of Anticonvulsant (AC) drugs. The aim of this article is to review the use of AC in the management of BWS and BD. MethodsMEDLINE and the Cochrane were searched, selecting studies from 1980 until 2014, in which a pharmacological intervention with classic and new AC was made for discontinuing long-term BZD use. ResultsIn regard to classic AC, there were identified 10 studies related to carbamazepine and 4 studies related to valproate. On one hand, whereas there is a great body of research involving carbamazepine and there is a consensus about its efficacy for discontinuing long-term BZD use, especially in terms of improving drug-free outcomes, there have been brought inconclusive results in regard to valproate. On the other hand, studies identified of the new AC are as follows: 2 for gabapentin, 2 for oxcarbazepine, 2 for pregabalin, 1 for tigabine and 2 for topiramate. With the exception of pregabalin, only small studies and cases report have been conducted for most of the new AC. Pregabalin has demonstrated to be effective in the treatment of BD and BWS, exerting its beneficial action by reducing the severity of withdrawal and anxiety symptoms. ConclusionTo date, among AC agents, only carbamazepine and pregabalin can be considered as augmentation alternatives for the treatment of long-term BZD use. Further randomized, double-blind, placebo-controlled studies are necessary to increase the knowledge to support the use of AC for the treatment of BD and BWS.

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“…The GABAA -PAM included four trials. Alpidem (46,47), and zolpidem (48,49) clustered into their pharmacology class showed limited efficacy in alleviating withdrawal symptoms (e.g., withdrawal insomnia) during BZD discontinuation, but the effect size was small, and the result was not statistically significant (d= 0.108, p=0.479). Heterogeneity was small: I 2 = 8.261%.…”

Section: Gaba a Receptor Positive Allosteric Modulatormentioning

confidence: 99%

Pharmacological class interventions for benzodiazepine withdrawal discontinuation: a meta-analysis

Fluyau

Revadigar

Mitra³

et al. 2020

Preprint

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Background Long-term benzodiazepine (BZD) use may lead to dependence, addiction, and neuropsychiatric disturbances. BZD discontinuation can cause severe withdrawal symptoms and resurgence of premorbid conditions. There are guidelines on how to stop BZD if it is necessary. Pharmacological management is an option among several other recommendations, but its benefit remains unclear. The current meta-analysis aims to supplement the existing literature by dividing the pharmacological agents studied for the management of BZD discontinuation into pharmacological classes according to the Neuroscience-based Nomenclature and to investigate whether these classes (e.g., BZD receptor antagonist) are efficient in managing and facilitating BZD withdrawal discontinuation. Methods Data collected from (1985 to 2018) in Google Scholar, Medline Ovid, Scopus, PsychInfo, ClinicalTrials.gov, Cochrane Review Database, Embase, Scopus, Pubmed, and Proquest databases; involved controlled clinical trials on drugs studied for BZD withdrawal discontinuation. Single drugs were clustered into their pharmacological class (domain). The Oxford Quality Scoring System assessed the quality of a trial. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) was used for clinical practice recommendations. For publication bias, we visually inspected the Funnel plot. We adopted the Cochrane Risk of Bias Tool to assess biases inherent to individual trials. The standardized mean difference measured the magnitude of the benefit of a pharmacological class. Results We analyzed forty-nine controlled trials of 2815 assigned participants. Of fourteen classes, the BZD receptor antagonist class (d 0.671, CI 0.199 -1.143, p=0.005, I2=0),5-HT1A receptor partial agonist, and the glutamate class seemed to have the potentiality to manage BZD withdrawal discontinuation clinically. Around 61 % of the trials received an Oxford Quality score of three, 86% of the trials were granted a GRADE recommendation low. About 29 trials were at low risk of bias in general. Conclusions Even though we could not prove that the pharmacological classes of drugs we analyzed for the clinical management of BZD withdrawal discontinuation were efficacious, our investigation showed that some of these classes have the potentiality to manage BZD withdrawal discontinuation and clinically facilitate the process when it is necessary, relevant, and recommended based on established guidelines. Further investigations are warranted to support our findings. Keywords: benzodiazepine withdrawal, benzodiazepine discontinuation, benzodiazepine cessation, benzodiazepine dependence.

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A randomized, double-blind study of alpidem vs placebo in the prevention and treatment of benzodiazepine withdrawal syndrome

Cited by 7 publications

References 24 publications

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Anticonvulsant Agents for the Management of Benzodiazepine Dependence

Pharmacological class interventions for benzodiazepine withdrawal discontinuation: a meta-analysis

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