The Benzodiazepines Crisis

Abstract When properly prescribed, benzodiazepines and related “Z” drugs, are usually safe and effective. However, some patients experience lack of efficacy, severe adverse effects, and/or protracted withdrawal symptoms. Unfortunately, there is no reliable way to predict outcome prior to treatment. Use has dramatically expanded, to the point where some experts suggest a disconnect with actual medical need. With increased and longer prescribing there has been a corresponding increase in the “down-side” of these drugs. Benzodiazepines, as all drugs, produce some degree of normal physiologic tolerance and physical dependence. But for some patients withdrawal can result in a bewildering array of symptoms, that can persist for protracted time periods, difficult to understand and live with. Although there is currently no clear mechanistic explanation, some potentials include alterations of receptor number, promoters of receptor protein synthesis or degradation, absorption, distribution, metabolism, and elimination, GABAA-receptor function or subtype-distribution, or involvement of peripheral benzodiazepine binding/receptor sites. This book attempts to bring benzodiazepine use under a more rational paradigm and reduce the incidence of side-effects and drug–drug interactions (DDI). It is the first devoted to take on this responsibility. Use, overuse/misuse, side-effects, DDI, physiology, and withdrawal are reviewed by expert clinicians and basic scientists in-depth. The book challenges the medical community to take seriously the use of this class of drug and to ameliorate prescribing behavior. The case is made for limiting initiation and duration (2–4 weeks) of use, and careful, supported discontinuation. We laud and suggest increased research into this class of drug and it’s “down-side.”