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Risk of death increases three-fold if patients co-prescribed methadone and benzodiazepines

GPs have been warned not to prescribe benzodiazepines with opioid agonist therapy after a new study found an increased risk of death from overdose when the drugs were co-prescribed.

Researchers found that although co-prescribing benzodiazepines with opioid agonist therapy (OAT), such as methadone or buprenorphine, in patients who were addicted to opioids increased the likelihood that they would stay on treatment, it also increased the risk of drug-related poisoning.

The study, published in PLOS Medicine, was carried out by researchers at the Universities of Bristol and Manchester and King’s College London and looked at data for over 12,000 patients prescribed OAT between 1998 and 2014.

Researchers found that patients who were co-prescribed a benzodiazepine with their OAT were almost three times as likely to die of a drug-related overdose as those who were not.

They also found that patients concurrently prescribed a benzodiazepine had a longer average OAT duration, with an average of 416 days, compared to 244 days in those not prescribed a benzodiazepine. They said however, that this was not linked with lower mortality.

The researchers said that some doctors may co-prescribe benzodiazepines and OAT despite warnings from guidelines not to, due to the perceived benefits of patients staying on treatment for longer, and uncertainty about whether co-prescribing is actually harmful. 

The authors said in the paper: ‘Our findings may have implications for clinical policy. Prescription of benzodiazepines to opioid-dependent patients during OAT or whilst still using illicit opioids should generally be avoided, other than when clinical judgement suggests that the benefits of this are likely to be greater than the harms. Clinical guidelines should emphasise this point.’

Research published in October found that patients were more likely to be prescribed benzodiazepines in the most deprived areas of England.

A study earlier this year found that opioid prescribing in England has ‘significantly’ increased over the last five years.


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