Agonist substitution—a treatment alternative for high‐dose benzodiazepine‐dependent patients?

Abstract

There is vast evidence for the superiority of agonist treatments (methadone, buprenorphine) over a withdrawal approach in opioid-dependent populations. Little research, however, has been conducted on the same approach for the treatment of high-dose benzodiazepine (BZD) dependence. Even large-scale reviews and meta-analyses discussing treatment strategies for benzodiazepine-dependent patients focus solely upon approaches that aim at achieving abstinence, namely on complete BZD withdrawal. While the types of interventions differ (e.g. gradual benzodiazepine taper with a long or a short half-life benzodiazepine, switching to non-benzodiazepine anxiolytics or prescribing adjunctive medications such as antidepressants or anticonvulsants on an in- or out-patient basis), the common aim of treatment still is total abstinence from benzodiazepines. However, the majority of patients suffering from high-dose BZD dependence do not succeed with long-term abstinence, irrespective of the procedure, and clinicians have been using BZD 'substitution' treatment in such cases for decades. Therefore, we suggest the evaluation of a substitution approach in this group, consisting of maintenance treatment with a slow-onset, long-acting BZD. Advantages of such a procedure may be improved health, less craving, fewer withdrawal complications, reduced anxiety, increased treatment retention, improvements in social functioning and less illegal activity. Cognitive impairments, the most problematic side effects of substitution treatment with benzodiazepines, could possibly be minimized by using an optimal agonist.

BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP

“…Both groups showed a reduction in benzodiazepine dosage of 86% to around 14 mg which was maintained at 1 month post-discharge. Liebrenz et al (2010) have proposed the need to evaluate agonist substitution treatment in high-dose benzodiazepine dependence, where individuals have not been able to undergo withdrawal. However, they recognise this needs to be balanced against the risks, particularly in regard to negative effects on cognition and memory.…”

Benzodiazepine Substitution for Dependent Patients—going With the Flow

“…Nevertheless, Lader et al [4] suggested that the substitution of diazepam for another BZD can be helpful, 'at least logistically', because diazepam is available in a liquid formulation. There are also a number of studies on optimal psychotherapeutic interventions [2,6,7], with cognitive-behavioural interventions probably having the best evidence.…”

“…Liebrenz et al [7] remind us of an uncomfortable truth; that despite all the good intentions and efforts to stop people taking benzodiazepines when they are dependent, they have failed and failed again, so that all that we can really recommend on the basis of good evidence is that benzodiazepines are reduced gradually [8]. Not only do people with high-dose dependence fail to withdraw successfully but those with low-dose dependence fail frequently too, and in personal studies we found attempts to persuade people not to take these drugs after they had been through the process of withdrawal successfully were thwarted; a majority returned to taking them in the longer term, not often regularly, but sufficiently to make a nonsense of the apparent triumph of stopping their drugs completely [9].…”

Flumazenil in treatment benzodiazepine withdrawal syndrome: Case report

“…From pioneering protocols introduced by Gilberto Gerra (working at Centro Studi Farmacotoxico Substance Abuse Service, Parma, Itally) [8,9] Further clinical practice and research confi rms that fl umazenil mainly acts as a "silent" receptor antagonist on the benzodiazepine receptor of the GABA-A complex, and is active only in the presence of benzodiazepines, replacing them, which explains its eff ect on reducing withdrawal symptoms and anxiety reduction. However, in certain circumstances, the modifi cation in the receptor complex GABA-A, which is the case with the long-term anxiety disorders (in panic disorder primarily) or in cooperation with chronic use of benzodiazepines, it can act as a benzodiazepine inverse agonist, i.e.…”