Challenges of the pharmacological management of benzodiazepine withdrawal, dependence, and discontinuation

Abstract

Background:Benzodiazepines (BZDs) are among the most prescribed sedative hypnotics and among the most misused and abused medications by patients, in parallel with opioids. It is estimated that more than 100 million Benzodiazepine (BZD) prescriptions were written in the United States in 2009. While medically useful, BZDs are potentially dangerous. The co-occurring abuse of opioids and BZD, as well as increases in BZD abuse, tolerance, dependence, and short- and long-term side effects, have prompted a worldwide discussion about the challenging aspects of medically managing the discontinuation of BZDs. Abrupt cessation can cause death. This paper addresses the challenges of medications suggested for the management of BZD discontinuation, their efficacy, the risks of abuse and associated medical complications. The focus of this review is on the challenges of several medications suggested for the management of BZD discontinuation, their efficacy, the risks of abuse, and associated medical complications.Methods:An electronic search was performed of Medline, Worldwide Science, Directory of Open Access Journals, Embase, Cochrane Library, Google Scholar, PubMed Central, and PubMed from 1990 to 2017. The review includes double-blind, placebo-controlled studies for the most part, open-label pilot studies, and animal studies, in addition to observational research. We expand the search to review articles, naturalistic studies, and to a lesser extent, letters to the editor/case reports. We exclude abstract and poster presentations, books, and book chapters.Results:The efficacy of these medications is not robust. While some of these medicines are relatively safe to use, some of them have a narrow therapeutic index, with severe, life-threatening side effects. Randomized studies have been limited. There is a paucity of comparative research. The review has several limitations. The quality of the documents varies according to whether they are randomized studies, nonrandomized studies, naturalistic studies, pilot studies, letters to the editors, or case reports.Conclusions:The use of medications for the discontinuation of BZDs seems appropriate. It is a challenge that requires further investigation through randomized clinical trials to maximize efficacy and to minimize additional risks and side effects.

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“…Even if all of these cases resulted from kava use, the estimated risk would be less than 0.3 cases per one million daily doses [ 167 , 173 ], which is still superior to some, if not all, commonly used anxiolytic agents. At the same time, stress and anxiety are becoming more prevalent among the general population [ 174 ], while current pharmacologic treatments have only a modest clinical effect and carry a high burden of side effects [ 175 , 176 ]. Thus, there is an unmet clinical need for novel anxiolytics to achieve better anxiety management with minimal adverse effects [ 177 ].…”

A tailored e-learning gives long-term changes in determinants of GPs’ benzodiazepines prescribing: a pretest-posttest study with self-report assessments

“…(BZDs) are commonly used psychotropic drugs for treating conditions such as insomnia and anxiety in primary care, although their long-term use is associated with considerable adverse effects [1][2][3]. Despite guidance advocating use of non-pharmacological, psychological treatments first-line (1), and restricting BZDs to only short-term use if needed (2), numerous studies have shown that BZDs are still overprescribed and commonly used long-term [4][5][6].…”

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“…[ 21 ] In the case of long-acting agents such as diazepam, withdrawal symptoms manifest only about 5–7 days after abrupt discontinuation, while they are more quickly evident in case of drugs like lorazepam. [ 22 ]…”