Lader Malcolm, Tylee Andre, Donoghue John
Institute of Psychiatry, King's College London, London, England.
CNS Drugs. 2009;23(1):19-34. doi: 10.2165/0023210-200923010-00002.
The use of benzodiazepine anxiolytics and hypnotics continues to excite controversy. Views differ from expert to expert and from country to country as to the extent of the problem, or even whether long-term benzodiazepine use actually constitutes a problem. The adverse effects of these drugs have been extensively documented and their effectiveness is being increasingly questioned. Discontinuation is usually beneficial as it is followed by improved psychomotor and cognitive functioning, particularly in the elderly. The potential for dependence and addiction have also become more apparent. The licensing of SSRIs for anxiety disorders has widened the prescribers' therapeutic choices (although this group of medications also have their own adverse effects). Melatonin agonists show promise in some forms of insomnia. Accordingly, it is now even more imperative that long-term benzodiazepine users be reviewed with respect to possible discontinuation. Strategies for discontinuation start with primary-care practitioners, who are still the main prescribers.This review sets out the stratagems that have been evaluated, concentrating on those of a pharmacological nature. Simple interventions include basic monitoring of repeat prescriptions and assessment by the doctor. Even a letter from the primary-care practitioner pointing out the continuing usage of benzodiazepines and questioning their need can result in reduction or cessation of use. Pharmacists also have a role to play in monitoring the use of benzodiazepines, although mobilizing their assistance is not yet routine. Such stratagems can avoid the use of specialist back-up services such as psychiatrists, home care, and addiction and alcohol misuse treatment facilities.Pharmacological interventions for benzodiazepine dependence have been reviewed in detail in a recent Cochrane review, but only eight studies proved adequate for analysis. Carbamazepine was the only drug that appeared to have any useful adjunctive properties for assisting in the discontinuation of benzodiazepines but the available data are insufficient for recommendations to be made regarding its use. Antidepressants can help if the patient is depressed before withdrawal or develops a depressive syndrome during withdrawal. The clearest strategy was to taper the medication; abrupt cessation can only be justified if a very serious adverse effect supervenes during treatment. No clear evidence suggests the optimum rate of tapering, and schedules vary from 4 weeks to several years. Our recommendation is to aim for withdrawal in <6 months, otherwise the withdrawal process can become the morbid focus of the patient's existence. Substitution of diazepam for another benzodiazepine can be helpful, at least logistically, as diazepam is available in a liquid formulation.Psychological interventions range from simple support through counselling to expert cognitive-behavioural therapy (CBT). Group therapy may be helpful as it at least provides support from other patients. The value of counselling is not established and it can be quite time consuming. CBT needs to be administered by fully trained and experienced personnel but seems effective, particularly in obviating relapse.The outcome of successful withdrawal is gratifying, both in terms of improved functioning and abstinence from the benzodiazepine usage. Economic benefits also ensue.Some of the principles of withdrawing benzodiazepines are listed. Antidepressants may be helpful, as may some symptomatic remedies. Care must be taken not to substitute one drug dependence problem for the original one.
苯二氮䓬类抗焦虑药和催眠药的使用一直备受争议。对于该问题的严重程度,甚至长期使用苯二氮䓬类药物是否真的构成问题,专家之间以及不同国家之间都存在不同观点。这些药物的不良反应已有大量记录,其有效性也越来越受到质疑。停药通常是有益的,因为停药后精神运动和认知功能会得到改善,尤其是在老年人中。药物依赖和成瘾的可能性也变得更加明显。选择性5-羟色胺再摄取抑制剂(SSRI)用于治疗焦虑症的获批,拓宽了处方医生的治疗选择范围(尽管这类药物也有其自身的不良反应)。褪黑素激动剂在某些形式的失眠症治疗中显示出前景。因此,现在更加迫切需要对长期使用苯二氮䓬类药物的患者进行停药可能性评估。停药策略首先由基层医疗从业者开始实施,他们仍然是主要的处方医生。本综述阐述了已评估的策略,重点关注那些具有药理学性质的策略。简单的干预措施包括对重复处方进行基本监测以及医生进行评估。即使是基层医疗从业者写一封信指出苯二氮䓬类药物的持续使用情况并质疑其必要性,也可能导致用药量减少或停药。药剂师在监测苯二氮䓬类药物的使用方面也能发挥作用,尽管动员他们提供帮助尚未成为常规做法。此类策略可以避免使用诸如精神科医生、家庭护理以及成瘾和酒精滥用治疗机构等专科后备服务。最近一篇考科蓝综述详细回顾了针对苯二氮䓬类药物依赖的药理学干预措施,但仅有八项研究被证明足以进行分析。卡马西平似乎是唯一一种在辅助停用苯二氮䓬类药物方面具有任何有用辅助特性的药物,但现有数据不足以就其使用提出建议。如果患者在停药前抑郁或在停药期间出现抑郁综合征,抗抑郁药可能会有所帮助。最明确的策略是逐渐减少用药量;只有在治疗期间出现非常严重的不良反应时,突然停药才是合理的。没有明确证据表明最佳的减药速度,减药时间表从4周到数年不等。我们的建议是目标在6个月内完成停药,否则停药过程可能会成为患者生活中的病态关注点。用另一种苯二氮䓬类药物替代地西泮可能会有帮助,至少在操作上是这样,因为地西泮有液体制剂。心理干预措施范围从通过咨询提供简单支持到专业的认知行为疗法(CBT)。团体治疗可能会有帮助,因为它至少能提供其他患者的支持。咨询的价值尚未得到证实,而且可能相当耗时。CBT需要由训练有素且经验丰富的人员实施,但似乎很有效,尤其是在避免复发方面。成功停药的结果是令人满意的,无论是在功能改善还是戒除苯二氮䓬类药物使用方面。还会带来经济效益。列出了停用苯二氮䓬类药物的一些原则。抗抑郁药可能会有帮助,一些对症治疗药物也可能有用。必须注意不要用一种药物依赖问题替代原来的问题。