International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications: IV. Therapeutic dose dependenceand abuse liability of benzodiazepines in the long-term treatment of anxiety disorders

Despite decades of relevant basic and clinical research, active debate cont inues about the appropriate extent and duration of benzodiazepine use in th e treatment of anxiety and related disorders. The primary basis of the cont roversy seems to be concern among clinicians, regulators, and the public ab out the dependence potential and the abuse liability of benzodiazepines. Th is article reports systematically elicited judgments on these issues by a r epresentative panel of 73 internationally recognized experts in the pharmac otherapy of anxiety and depressive disorders, a panel which was constituted by a multistage process of peer nomination. The criterion for inclusion at each stage was the nomination by at least two peers as one of the "profess ionally most respected physicians of the world with extensive experience an d knowledge in the pharmacotherapy of anxiety and depressive disorders." Si xty-six respondents (90%) completed a comprehensive questionnaire covering a wide range of topics relevant to the therapeutic use of benzodiazepines a nd other medications that might be used for the same purposes. Overall, the expert panel judged that benzodiazepines pose a higher risk of dependence and abuse than most potential substitutes but a lower risk than older sedat ives and recognized drugs of abuse. There was Little consensus about the re lative risk of dependence and abuse among the benzodiazepines. Differences between benzodiazepines with shorter and longer half-lives in inducing with drawal symptoms are much less clear during tapered than during abrupt disco ntinuation. There was little agreement about the most important factors con tributing to withdrawal symptoms and failure to discontinue benzodiazepines . The pharmacologic properties of the medication may be the most important contributors to withdrawal symptoms. In contrast, the clinical characterist ics of the patient may be the most important contributors to failure to dis continue medication. The experts' judgment seems to support the widespread use of benzodiazepines for the treatment of bona fide anxiety disorders, ev en over long periods. The experts generally viewed dependence and abuse lia bility as clinical issues amenable to appropriate management, as for other adverse events related to therapy. However, more definitive clinical resear ch on the remaining controversial issues is urgently needed to promote opti mal patient care.