Millions of Britons taking widely prescribed painkillers could be unwittingly putting themselves at risk of drug poisoning, researchers have warned.
A new study from University College London (UCL) found that people taking gabapentinoids were at increased risk of severe side effects if they combined the drug with other common medications.
Taking benzodiazepines – sedatives such as diazepam and valium, used to treat anxiety and insomnia – alongside gabapentinoids doubled the risk of hospitalisation for drug poisoning, researchers found.
Meanwhile opioids – such as codeine, tramadol and morphine – taken with gabapentinoids was associated with a 30 per cent increased risk of hospitalisation.
Despite these risks, nearly 90 per cent of patients involved in the study had been prescribed opioids alongside gabapentinoids, while more than half had also been put on benzodiazepines.
‘Prescription rates for gabapentinoids have been increasing rapidly in recent years, as they are seen as a safe alternative to opioids,’ said the study’s lead author, Dr Kenneth Man.
‘While they can be effective for pain relief and do have better perceived safety profiles than opioids, there are still substantial risks that clinicians and patients should be mindful of.’
More than 4.5million people in England are prescribed a gabapentinoid each year, most commonly in the form of gabapentin or pregabalin.
The drugs are also the seventh highest prescribed medication in the US, while previous UCL research found their global use across 65 countries had increased more than four times between 2008 and 2018.
To determine the safety of gabapentinoids, researchers reviewed UK data from 16,827 people prescribed the drugs between 2010 and 2020.
They examined hospital admissions for drug poisoning before, during and after the treatment, while analysing which other medications had also been prescribed.
This was then whittled down to patients who had experienced at least one hospitalisation for drug poisoning – just under two per cent of those prescribed a gabapentinoid during the study period.
Up to 10 years of data for each individual was analysed, allowing researchers to compare periods when the same person was not taking the drugs.
Symptoms of drug poisoning can range from confusion and nausea to seizures, airway blockages and death. Severe cases require hospitalisation, where doctors can reverse the poisoning with counteracting drugs.
Nearly 10,000 Britons are taken to hospital each year for drug poisoning.
The study uncovered a range of intentional and accidental poisoning cases involving gabapentinoid, including incidents involving misuse or doses above those prescribed.
People taking both a gabapentinoid and a benzodiazepine were found to be four times more likely to be hospitalised for drug poisoning in the first four weeks after starting treatment, compared with times when they were taking neither drug.
Combining a gabapentinoid with an opioid was found to double the risk over the same period.
Researchers also found that 89 per cent of participants took gabapentinoids alongside opioids at some point during the study, while 55 per cent were also prescribed benzodiazepines for part of the time.
Gabapentinoids were often prescribed when patients are already at greater risk of drug poisoning, they discovered, such as when their symptoms are worsening.
The study’s first author, Dr Andrew Yuen said: ‘A clinician’s decision to prescribe gabapentinoids may sometimes be an attempt to minimise the risk of drug poisoning linked to opioids or other medications.
‘While the risk of poisoning did decrease somewhat after patients began gabapentinoid treatment, they still faced an elevated risk of drug poisoning, which suggests that clinicians need to remain vigilant to the risks.’
Dr Kenneth Man added: ‘Our findings do not suggest that gabapentinoids are unsafe or should not be prescribed, but clinicians should be cautious when prescribing them, particularly if a patient is taking other medications as well, and clinicians should closely monitor patients who are taking them.’
The findings come months after an announcement by the Medicines and Healthcare products Regulatory Agency (MHRA), which increased warnings on gabapentinoids over addiction, dependence, withdrawal and tolerance.
The MHRA ordered the move after a safety review flagged risks linked to gabapentinoid painkillers, benzodiazepine tranquillisers and Z-drugs used for sleep.
Patient information leaflets covering treatments for conditions ranging from nerve pain to sleep disorders will now carry the warning: ‘May cause addiction, dependence and withdrawal reactions’.
As part of the review, the Commission on Human Medicines backed changes not only to packaging and patient information leaflets, but also stronger warnings not to combine the medicines with opioids or alcohol, and not to share them with others.
The drugs act on GABA pathways in the brain to relieve pain and produce sedative effects, but long-term use has been found to lead to physical dependence and difficult withdrawal for some patients.
Addiction clinics have reported patients turning to online sellers or street dealers after building tolerance and needing higher doses to feel the effects.
