Concurrent Use of Benzodiazepine with Buprenorphine and Potential Risks for ADRs and Overdose




Sureja, Rushil
Slate, Bradley
White, Annesha
Vernachio, Kimberly


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Objective: Benzodiazepines (BZDs) are known to negate the “plateau” properties of buprenorphine, concealing the purported safety advantages of buprenorphine vs. other opioids. One question is, does the literature show an increase in overdose or respiratory depression when these two drugs are combined, and whether the benefits of using the combination equal the risk of other opioids that do not have buprenorphine’s partial agonist/antagonist properties? The objective of this study was to examine the literature within the last decade and determine if combined use of BZDs with buprenorphine increased the risk for adverse drug reactions or overdose. Methods: Journal articles were retrieved through the databases PubMed and Google Scholar from January 2007 to January 2017. The journal articles keywords were: ‘BZDs, ‘buprenorphine’, ‘pain’, and ‘opioids’. Articles were selected to include adverse effect, overdose, and death-potential when BZDs were used with buprenorphine. Articles that focused on the effect that dose or formulation had on severity were utilized to give context to the severity of coadministration. The articles were graded using Oxford Center of Evidence Based Medicine to address bias. Results: A total of eight peer-reviewed studies were used, representing both randomized controlled trials and observational studies. The sample sizes of the examined studies ranged from 72 to 692. Due to the low number of existing studies at this time, there is insufficient evidence to determine if the benefits of concurrent use of BZDs and buprenorphine outweigh the risks of serious, and sometimes fatal, adverse effects. However, animal research revealed that using a lower strength BZD will reduce adverse effects significantly. Conclusions: The literature supports the risk of accidental overdose and death in the use of opioids and BZDs. Although there is little published research, there is support for our hypothesis in that a significant degree of adverse events and overdose were realized once the buprenorphine component was added to BZDs. There appears to be a large amount of variability in severity depending on the administered dose. Future research, including an observational study, will provide valuable information.