Update
Benzodiazepine dependence: Focus on withdrawal syndromeDépendance aux benzodiazépines : le syndrome de sevrage

https://doi.org/10.1016/j.pharma.2009.07.001Get rights and content

Summary

Benzodiazepines are potentially addictive drugs: psychological and physical dependence can develop within a few weeks or years of regular or repeated use. The socioeconomic costs of the present high level of long-term benzodiazepine use are considerable. These consequences could be minimised if prescriptions for long-term benzodiazepines were decreased. However, many physicians continue to prescribe benzodiazepines and patients wishing to withdraw receive little advice or support. Particular care should be taken in prescribing benzodiazepines for vulnerable patients such as elderly persons, pregnant women, children, alcohol- or drug-dependent patients and patients with comorbid psychiatric disorders. The following update gives recent research results on the withdrawal pathophysiology and practical information in order to treat or prevent benzodiazepine withdrawal syndrome.

Résumé

Les benzodiazépines anxiolytiques et hypnotiques sont des médicaments dont le potentiel addictif est maintenant bien connu. L’utilisation de ces molécules sur de longues périodes allant de plusieurs semaines à plusieurs années provoque des manifestations psychiques et physiques de dépendance dont le coût socioéconomique, bien que difficile à estimer, semble être très important compte tenu de leur large prescription. Le respect des recommandations pour leur prescription, la sensibilisation des médecins et pharmaciens à cette dépendance trop souvent sous-estimée et la multiplication des actions d’information envers les patients devraient participer à minimiser le mésusage des benzodiazépines. Certaines populations de patients telles que les sujets âgés, les femmes enceintes, les enfants, les patients présentant une autre addiction ou une pathologie psychiatrique doivent faire l’objet d’une attention particulière vis-à-vis de ce risque de dépendance aux benzodiazépines. Cet article met à jour notamment les connaissances concernant la physiopathologie et la prise en charge de ce syndrome de sevrage.

Introduction

Although recommendations for benzodiazepine use with prescription suggest that duration be limited to a few weeks, patients are known to take these drugs for months, years, or even decades. In the 1996 Australian National Health Survey, 58% of the 359,300 benzodiazepine users had been taking this medication for at least 6 months and in another study, 84% of 3234 benzodiazepine users identified in a study of 15 general practices were still using them 8 months later [1], [2]. According to different National and European epidemiological surveys, France had the highest annual rate of anxiolytic use, within a range of 12% to 19%. Duration of benzodiazepine use was more than 6 months in 70 to 75% of users and increased with age [3], [4]. Such long-term use occurs in spite of evidence that the benefits of benzodiazepine may decrease with time, while the potential for adverse effects remains. Potential adverse effects include cognitive decline, unwanted sedation, reduced coordination, increases in risk of accidents, as well as psychological and physical dependence (Table 1). Benzodiazepines have long been known to cause amnesia, an effect that is utilised when the drugs are used as premedication before major surgery or for minor surgical procedures. Oral doses of benzodiazepines in the dosage range used for insomnia or anxiety can also cause episodic memory impairment. Acquisition of new information is deficient, partly because of lack of concentration and attention [5]. According to Neutel [6], the overriding factor associated with likelihood of benzodiazepine use was that of previous use. Other factors associated with benzodiazepine use, whether related to the person or the reason for benzodiazepine use, were considerably less important for long-term users. It may be concluded that once benzodiazepine use has started, specific reasons such as poor health pain or chronic diseases become much less important in long-term use than they are in the earlier phases of benzodiazepine use.

In clinical practice, benzodiazepines should be used for acute anxiety management rather than long-term treatment. However, benzodiazepines continue to be frequently prescribed for the initial treatment of panic disorders, as well as other anxiety disorders and chronic insomnia. These medications are undoubtedly drugs associated with problems on attempted reduction in dosage or withdrawal. The discontinuation syndrome can be severe and can prevent the long-term user from ever stopping the medication. In this update on benzodiazepine withdrawal syndrome, we attempted to explain who is vulnerable, why this syndrome exists and how to withdraw from these drugs.

Section snippets

Vulnerable patients to withdrawal symptoms

Particular care should be taken in prescribing benzodiazepines for vulnerable patients such as elderly, pregnant women and the foetus, children, alcohol and drug abuse dependent patients and patients with comorbid psychiatric disorders.

Clinical aspects

The development of tolerance is one of the reasons people become dependent on benzodiazepines and also sets the scene for the withdrawal syndrome. This syndrome is a key sign of benzodiazepine dependence. Withdrawal symptoms occur when there is a decline in the blood or tissue concentration of any dependence-forming substance that an individual has been continuously taking. These symptoms are generally the opposite of the acute effects of the drug, or they may mimic the symptoms for which the

Biological aspects

The pharmacological mechanisms underlying benzodiazepine withdrawal are complex and still not clear. The result of a rapid or abrupt withdrawal of the benzodiazepine is underactivity of inhibitory GABA (γ-aminobutyric acid) functions and a surge in excitatory nervous activity, giving rise to many of the benzodiazepine symptoms.

First, it is well-established that following chronic exposure to benzodiazepines, there are alterations in GABAergic neurotransmission (up/down regulation GABA-a receptor

Clinical management

Why stopping benzodiazepine? Because long-term use of benzodiazepines can give rise to many unwanted effects, including poor memory and cognition, emotional blunting, depression, increasing anxiety, physical symptoms and dependence, with important social and economic consequences. All benzodiazepines can produce these effects whether taken as anti-anxiety drugs or sleeping pills. Several clinical options exist for discontinuing benzodiazepine treatment, including gradual tapering of the current

Conclusions

The socioeconomic costs of the present high level of long-term benzodiazepine use are considerable, although difficult to quantify. These consequences could be minimised if prescriptions for long-term benzodiazepines were decreased. Yet, many doctors continue to prescribe benzodiazepines and patients wishing to withdraw receive little advice or support on how to go about it.

Due to the variability in medications and research designs, it is not possible to assess conditions under which

Conflicts of interest

None.

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