Ashton H. The diagnosis and management of benzodiazepine dependence. Curr Opin Psychiatry 18: 249-255

Department of Psychiatry, University of Newcastle upon Tyne, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Current Opinion in Psychiatry (Impact Factor: 3.94). 06/2005; 18(3):249-55. DOI: 10.1097/01.yco.0000165594.60434.84
Source: PubMed


Despite repeated recommendations to limit benzodiazepines to short-term use (2-4 weeks), doctors worldwide are still prescribing them for months or years. This over-prescribing has resulted in large populations of long-term users who have become dependent on benzodiazepines and has also led to leakage of benzodiazepines into the illicit drug market. This review outlines the risks of long-term benzodiazepine use, gives guidelines on the management of benzodiazepine withdrawal and suggests ways in which dependence can be prevented.
Recent literature shows that benzodiazepines have all the characteristics of drugs of dependence and that they are inappropriately prescribed for many patients, including those with physical and psychiatric problems, elderly residents of care homes and those with comorbid alcohol and substance abuse. Many trials have investigated methods of benzodiazepine withdrawal, of which the keystones are gradual dosage tapering and psychological support when necessary. Several studies have shown that mental and physical health and cognitive performance improve after withdrawal, especially in elderly patients taking benzodiazepine hypnotics, who comprise a large proportion of the dependent population.
Benzodiazepine dependence could be prevented by adherence to recommendations for short-term prescribing (2-4 weeks only when possible). Withdrawal of benzodiazepines from dependent patients is feasible and need not be traumatic if judiciously, and often individually, managed.

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    • "These medications, especially BZD, are sometimes associated with adverse effects and are not suitable for long-term use due to an increased risk of life-threatening multiple drug overdoses. In opiate-dependent patients, the misuse and abuse of BZD is a public health problem because methadone and BZD both have sedating effects on the central nervous system, which lead to difficulty in breathing as well as cognitive impairment [27] [28]. A recent survey revealed a 47% prevalence of lifetime use of BZD among methadonemaintained patients [29] and nonprescribed BZD use among MMT patients ranged from 44 to 66% [30] [31]. "
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    ABSTRACT: Methadone maintenance therapy is an effective treatment for opiate dependence, but more than three-quarters of persons receiving the treatment report sleep quality disturbances. In this double-blind, randomized, controlled trial, we recruited 90 individuals receiving methadone for at least one month who reported sleep disturbances and had Pittsburgh Sleep Quality Index (PSQI) scores > 5. The purpose of this study was to determine whether Suan Zao Ren Tang, one of the most commonly prescribed traditional Chinese medications for treatment of insomnia, improves subjective sleep among methadone-maintained persons with disturbed sleep quality. Ninety patients were randomly assigned to intervention group (n = 45) and placebo group (n = 45), and all participants were analyzed. Compared with placebo treatment, Suan Zao Ren Tang treatment for four weeks produced a statistically significant improvement in the mean total PSQI scores (P = 0.007) and average sleep efficiency (P = 0.017). All adverse events (e.g., lethargy, diarrhea, and dizziness) were mild in severity. Suan Zao Ren Tang is effective for improving sleep quality and sleep efficiency among methadone-maintained patients with sleep complaints.
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    • "After informed consent and baseline examinations, all trial participants were instructed to gradually reduce their usual benzodiazepine dosage (including benzodiazepine-related drugs) at an approximate rate of 10 – 20% every second week. This rate of benzodiazepine tapering has been recommended internationally (Ashton 2005). We aimed for this withdrawal rate as the fi rst steps of tapering. "
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    ABSTRACT: We assessed if prolonged-release melatonin can facilitate withdrawal of long-term benzodiazepine usage in patients with schizophrenia or bipolar disorder. Randomised, placebo-controlled, blinded, parallel superiority trial of 24 weeks duration. Participants were randomised to prolonged-release melatonin 2 mg daily versus matching placebo and were continuously guided to gradually reduce their usual benzodiazepine dosage. The primary outcome was mean benzodiazepine daily dosage at 24 weeks. Secondary outcomes included pattern of benzodiazepine dosage over time, benzodiazepine cessation proportion, and benzodiazepine withdrawal symptoms. In total, 86 patients (21-74 years) were enrolled: 42 were randomised to melatonin versus 44 to placebo. We found no significant effect of melatonin on mean benzodiazepine dosage at 24 weeks (melatonin group 8.01 mg versus placebo group 5.72 mg diazepam equivalents; difference between means -2.29; 95% CI -5.78 to 1.21; P = 0.20). Benzodiazepine cessation proportion was 38.1% (16/42) in the melatonin group versus 47.7% (21/44) in the placebo group (OR 0.64; 95% CI 0.26 to 1.56; P = 0.32). Prolonged-release melatonin had no effect on benzodiazepine withdrawal symptoms. Benzodiazepine dosage was comparably low between the groups after 24 weeks of guided gradual dose reduction. In this context, prolonged-release melatonin did not seem to further facilitate benzodiazepine discontinuation.
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    • "The chronic use of benzodiazepines may decrease the efficacy of GABA A receptors, which contributes to the development of tolerance , and abrupt discontinuation may cause a withdrawal syndrome characterized by intense anxiety, agitation and insomnia, memory and concentration impairments, among other symptoms [5]. This withdrawal is frequent with an incidence reported between 30 and 100% in different studies [8] and with potential high severity . The non-prescribed use of benzodiazepines can be associated with the use of illicit drugs and alcohol. "
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    ABSTRACT: There is a high rate of benzodiazepine use in the population. Benzodiazepines are used for multiple indications (anxiety, seizures, alcohol withdrawal, muscular relaxation and anesthesia). Benzodiazepines are also addictive substances and a non-negligible fraction of regular users will develop dependence. There is currently no approved pharmacotherapy for benzodiazepine use disorder treatment and optimal strategies for treatment are unclear. In this review, we aimed to summarize the findings on off-label pharmacologic therapy that have been used for BZD dependence. One classical approach consists at providing a slow taper associated with counseling. Anti-epileptic drugs appear also to alleviate symptoms of withdrawal. The long-term strategies of maintenance therapy (with benzodiazepine) or of blocking therapy (with a GABA antagonist such as flumazenil) could provide some clinical benefit but have not yet been tested appropriately. Pregabalin appears promising and deserves further investigation. There is a clear need for more clinical trials in this area to improve care.
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