Pregabalin as adjunctive therapy in benzodiazepine discontinuation

Abstract

Purpose: The available evidence for the use of pregabalin as adjunctive therapy in the discontinuation of benzodiazepines is reviewed.

Summary: Pregabalin has been studied as an adjunctive pharmacologic treatment for the discontinuation of long-term benzodiazepine use. Unlike carbamazepine, pregabalin has little potential for drug interactions, and its adverse effects are mostly mild and transient. Pregabalin reduces the release of excitatory neurotransmitters by binding to regulatory subunits of voltage-activated calcium channels. The majority of studies evaluated failed to find a significant difference in benzodiazepine discontinuation rates between pregabalin and comparator groups. The long-term efficacy of pregabalin in benzodiazepine discontinuation is also unknown, as patients were only followed for 0-12 weeks after discontinuing the benzodiazepines. Most studies, however, did observe consistent improvement in withdrawal symptoms, anxiety symptoms, and cognitive function with pregabalin use in benzodiazepine discontinuation. Studies varied in design elements, such as whether past benzodiazepine discontinuation attempts occurred, baseline benzodiazepine use characteristics (agent, dose, duration), benzodiazepine discontinuation strategies previously used, and the use of comorbid psychiatric diagnoses and concurrent psychotropics as exclusion criteria. In addition, the literature does not clearly describe whether patients successfully discontinued pregabalin, for which there are reports of substance abuse.

Conclusion: Based on the current available evidence, pregabalin is not recommended for use in benzodiazepine discontinuation, as the majority of studies did not find a significant difference in benzodiazepine discontinuation rates between pregabalin and comparatory groups despite an improvement in withdrawal and anxiety symptoms.

Keywords: adverse effects; anxiety; substance withdrawal; substance-related disorders.