In a new study, researchers found that doctors should avoid co-prescribing benzodiazepines to opioid-dependent patients who are being treated with methadone or buprenorphine, also known as opioid agonist treatment (OAT), due to a three-fold increase in the risk of overdose death.
This increase in overdose death risk was also observed in patients who had recently left OAT. This is probably because these individuals continued to use opioid drugs after leaving treatment.
This was an observational study involving the analysis of data from the UK Clinical Practice Research Datalink of over 12,000 patients aged 15-64 who were prescribed OAT between 1998 and 2014.
Causes of death were found for over 7,000 of these patients through linking records with death data from the Office for National Statistics.
The research was led by a team at the University of Bristol.
Benzodiazepines are sedatives that are often prescribed to people who are opioid-dependent despite the discouragement of this practice in guidelines.
Doctors may be ignoring this guidance, in part because there is evidence that patients receiving both medicines together stay in treatment longer and because opioid-dependent patients have high levels of anxiety, which benzodiazepines can help relieve.
The new study suggests that, despite the benefits of longer treatment duration, the combination of benzodiazepines with opioid substitute therapy, also known as opioid agonist treatment (OAT), leads to a greater risk of overdose death than for those receiving OAT alone.
This pattern wasn’t seen as clearly for the other co-prescribed sedatives in the study, z-drugs (zaleplon, zolpidem and zopicolone) and gabapentinoids.
The team says that deaths in opioid-dependent people are increasing despite the fact that many receive opioid agonist treatment, which is known to reduce the overall risk of death compared to no treatment.
The clear association between co-prescribing benzodiazepines in patients receiving OAT, or who have recently left OAT, and an increased risk of overdose death suggests that doctors should consider changing their prescribing practice.
There may be unusual circumstances where co-prescription is clinically justified but these should be the exception rather than the rule.
The lead author of the study is John Macleod, Professor of Primary Care at the University of Bristol’s Centre for Academic Primary Care.
The study is published in PLOS Medicine.
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