Pharmacological class interventions for benzodiazepine withdrawal discontinuation: a meta-analysis

Abstract

<jats:p>Background Long-term benzodiazepine (BZD) use may lead to dependence, addiction, and neuropsychiatric disturbances. BZD discontinuation can cause severe withdrawal symptoms and resurgence of premorbid conditions. There are guidelines on how to stop BZD if it is necessary. Pharmacological management is an option among several other recommendations, but its benefit remains unclear. The current meta-analysis aims to supplement the existing literature by dividing the pharmacological agents studied for the management of BZD discontinuation into pharmacological classes according to the Neuroscience-based Nomenclature and to investigate whether these classes (e.g., BZD receptor antagonist) are efficient in managing and facilitating BZD withdrawal discontinuation. Methods Data collected from (1985 to 2018) in Google Scholar, Medline Ovid, Scopus, PsychInfo, ClinicalTrials.gov, Cochrane Review Database, Embase, Scopus, Pubmed, and Proquest databases; involved controlled clinical trials on drugs studied for BZD withdrawal discontinuation. Single drugs were clustered into their pharmacological class (domain). The Oxford Quality Scoring System assessed the quality of a trial. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) was used for clinical practice recommendations. For publication bias, we visually inspected the Funnel plot. We adopted the Cochrane Risk of Bias Tool to assess biases inherent to individual trials. The standardized mean difference measured the magnitude of the benefit of a pharmacological class. Results We analyzed forty-nine controlled trials of 2815 assigned participants. Of fourteen classes, the BZD receptor antagonist class (d 0.671, CI 0.199 -1.143, p=0.005, I2=0),5-HT1A receptor partial agonist, and the glutamate class seemed to have the potentiality to manage BZD withdrawal discontinuation clinically. Around 61 % of the trials received an Oxford Quality score of three, 86% of the trials were granted a GRADE recommendation low. About 29 trials were at low risk of bias in general. Conclusions Even though we could not prove that the pharmacological classes of drugs we analyzed for the clinical management of BZD withdrawal discontinuation were efficacious, our investigation showed that some of these classes have the potentiality to manage BZD withdrawal discontinuation and clinically facilitate the process when it is necessary, relevant, and recommended based on established guidelines. Further investigations are warranted to support our findings. Keywords: benzodiazepine withdrawal, benzodiazepine discontinuation, benzodiazepine cessation, benzodiazepine dependence.</jats:p>