In the setting of open-access opioid treatment programs (OTPs), the authors of this study in Drug and Alcohol Dependence sought to determine if patients with benzodiazepine exposure at study entry would have retention rates similar to those without benzodiazepine exposure. Comparing the retention rate for the two groups, the authors found that baseline benzodiazepine exposure had no impact on 12-month retention in the methadone program. These findings support U.S. Food and Drug Administration (FDA) recommendations to not withhold medications for opioid use disorder (OUD) in patients using benzodiazepines.
This was a retrospective study of 2,968 patients consecutively started on methadone treatment between January 2015 and February 2017.
The study site was the APT Foundation, a not-for-profit, community-based open-access OTP in New Haven, Connecticut. The sample was separated into benzodiazepine-exposed and benzodiazepine-nonexposed patients, based on results of a standard immunoassay urine toxicology test at study intake. The authors believe this is the first study to examine the impact of benzodiazepine exposure on treatment retention and duration in an open-access methadone treatment setting.
Retained at 12 months were 31% of patients with benzodiazepine exposure and 31% without benzodiazepine exposure. (Notably, retention rates were relatively low in this study, regardless of benzodiazepine exposure.) Median treatment duration was 182 days for patients with benzodiazepine exposure and 175 days for those without benzodiazepine exposure. Statistical analyses showed no significant difference in treatment duration between groups, and no difference in treatment retention between groups.
The authors concluded:
In this cohort of patients receiving methadone at an open-access OTP, benzodiazepine exposure at intake was not observed to impact 12-month treatment retention or duration. These findings support U.S. FDA recommendations to not withhold medications for opioid use disorder from patients taking benzodiazepines.
More research is needed to clarify patient-level and program factors influencing methadone treatment retention among individuals using benzodiazepines.
The study was supported by a grant from the National Institute on Drug Abuse (NIDA).
Relevance of the Study
Some background information will help in understanding the relevance of this study.
Patients with OUD often take benzodiazepines, either nonmedically or prescribed to manage symptoms such as anxiety and insomnia. Some studies have found a possible risk of serious side effects or methadone discontinuation when a benzodiazepine is added to the regimen. In 2016 the FDA released a communication advising clinicians to avoid combining benzodiazepines or other central nervous system depressants with opioid pain or cough medications, such as oxycodone, because such use “has resulted in serious side effects, including slowed or difficult breathing and deaths.”
But as the opioid crisis worsened, increases in overdose deaths involving highly potent opioids, such as fentanyl, raised concerns that the possible harm from untreated OUD could outweigh the possible harm of combining a benzodiazepine and methadone. In 2017, the FDA updated its earlier communication. Methadone and buprenorphine, it now stated, should not be withheld from patients taking benzodiazepines.
Yet even today, the authors note, “clinicians continue to face challenges assessing risks of benzodiazepine use among patients with OUD that may influence decisions to initiate, dose reduce, or discontinue MOUD [medications for opioid use disorder], particularly with the full opioid agonist, methadone.”
Discharge Factors: Patient Dropout vs. OTP Program Factors
Treatment discontinuation often is considered “patient dropout,” but program factors also play a role in treatment discharge, and may affect retention estimates. New treatment models—low threshold and open access—can find and remove program factors that contribute to methadone discontinuation.
Low-threshold programs have fewer restrictive policies and emphasize harm reduction; they are less likely to discharge patients for nonpayment or for continuing substance use
- Open-access models offer walk-in hours and welcome all patients without an appointment; patients can start methadone treatment immediately
- Combination programs: some open-access programs have a low-threshold approach, minimizing restrictive policies
Emphasizing the usefulness of their study, the authors point out that in addition to specifying program factors “in a unique, open-access treatment setting,” the study “adds to the existing literature by providing real-world data among a large cohort of nearly 3000 patients.”
Important limitations of this study: Analysis was based on benzodiazepine exposure at baseline, determined by the results of urine toxicology studies; ongoing benzodiazepine use was not factored in. The authors believe this may explain why the rates of benzodiazepine exposure are lower in this study than in previous studies.
Morford KL, Tetrault JM, Zhou B, et al. The impact of benzodiazepine exposure on treatment retention in an open-access methadone program: A retrospective cohort study [published online ahead of print, 2022 Nov 19]. Drug Alcohol Depend. 2022;241:109707. doi:10.1016/j.drugalcdep.2022.109707