There are 28 million Britons living with chronic pain, according to the British Pain Society.
Many of them rely on pills to help them get through each day. Yet as the Mail has highlighted so many times, these drugs can be highly addictive — and are linked to serious side-effects as well as crippling withdrawal symptoms.
As many as one in four people in the UK is now being prescribed drugs for pain, depression or anxiety that carry the risk of dependence, according to a report on prescription pill dependency published by Public Health England (PHE) earlier this month.
Concern about opioids (as well as benzodiazepines, known as benzos, and antidepressants for anxiety and sleeping problems) is putting pressure on GPs to reduce prescriptions.
But there are further fears that this is leaving the UK wide open to another pain prescription drug crisis — this time with gabapentinoids (GABA), including pregabalin (brand name Lyrica) and gabapentin (Neurontin).
There are new fears that the UK is being left wide open to another pain prescription drug crisis with gabapentinoids (GABA). Sarah Jolly, 34, died last year from an accidental overdose of pregabalin, prescribed for back pain since 2014
As the Mail launches a series on how to beat pain this Saturday as part of the Good Health for Life month, we focus on this worrying shift towards GABA drugs.
These drugs act on GABA, a chemical messenger in the brain that acts as a brake on over-excited nerve cells. They are licensed to treat epilepsy and nerve pain (the best evidence is for their use in post-shingles and diabetes-related nerve pain).
In the last year, 1.5 million Britons were prescribed gabapentinoids, according to the PHE report.
NHS figures also reveal that prescriptions have rocketed in the past ten years, from one million for pregabalin in 2008 to seven million in 2018; gabapentin prescriptions rose from 1.75 million to 7.3 million over the same period.
Alarm bells have been ringing about GABA drugs for a number of reasons, not least that they’re often prescribed ‘off-label’ (to treat a condition for which they’re not licensed) for things such as lower back pain — and for which there is little or no evidence that they work.
The drugs can cause unpleasant side-effects, including weight gain and memory problems, and there’s growing evidence of their potential for addiction. They are reported to cause significant withdrawal symptoms including nerve pain, anxiety, sleep problems, nausea and excessive sweating.
New research suggests pregabalin is associated with an increased risk of suicidal behaviour, road traffic incidents, violent behaviour and accidental overdose.
little evidence they work for pain
off-label uses account for a shocking 50 per cent of GABA prescriptions, according to a study of UK general practice records in the journal JAMA Network in 2018.
GABA drugs are being prescribed in place of benzos or opioids — ‘in the likely mistaken belief they are less liable to misuse or dependence and the lack of awareness of withdrawal problems that can arise’, says the PHE report.
In other words, these drugs are not only ineffective for conditions such as lower back pain, patients may also struggle to come off them
The PHE report was highly critical of the way prescribing patterns with opioids and benzodiazepines appear to be repeating themselves with GABA drugs, with one problem simply replaced by another.
Natalia Buzzeo, 27, went on pregabalin after being injured in a car crash in 2012. Yet Natalia says almost immediately she felt ‘like a zombie’. ‘I’d always been popular, but my personality changed – I fell out with people, lost friends and eventually my relationship with my boyfriend broke down’
‘I am as worried about pregabalin and gabapentin as I am about opioids,’ says Dr Cathy Stannard, a consultant in complex pain management at Gloucestershire Clinical Commissioning Group ‘They are just as problematic.’
‘Prescriptions are going up despite the fact they aren’t that effective for many types of pain. A lot of patients who take pregabalin ask to be tested for dementia because the memory problems it can cause are so bad,’ she adds.
‘Another side-effect is ataxia, lack of muscle coordination, which can lead to staggering and falling over.’ (And that is an issue, as 80 to 84-year-olds are the most likely to be prescribed GABA drugs, according to the PHE report.)
Concerns have been heightened by University of Oxford research published in The British Medical Journal in June, which found an increased risk of suicidal behaviour, accidental overdoses, road traffic accidents and offences, and injuries to the head and body in people on pregabalin.
The findings were based on 200,000 patients prescribed GABA drugs between 2006 and 2013.
Patients aged 15 to 24 who took pregabalin had a 70 per cent increased risk of suicidal behaviour, a 140 per cent increased risk of accidental overdose, a 113 per cent increased risk of head injuries, a 49 per cent increased risk of a road traffic incident and a 58 per cent increased risk of being arrested for a violent crime, Seena Fazel, a professor of forensic psychiatry who led the study, told Good Health.
It’s thought that because younger people are faster metabolisers, their bodies eliminate the drug faster, causing withdrawal symptoms and, in turn, impulsive behaviour and risk-taking.
Pfizer, the pharmaceutical company which makes pregabalin and gabapentin, says the research ‘was an observational study and therefore the findings should not imply causality’.
However Professor Fazel warns that if the findings are confirmed by other research, then the guidelines for prescriptions for younger people may need urgent review.
Dr Derek Tracy, a consultant psychiatrist at Oxleas NHS Foundation Trust in Bexley, says Professor Fazel’s research confirms for the first time that accidental overdose is a problem.
‘You could envisage a scenario where a drug prescribed for pain isn’t working, so a patient takes more, unaware of the risks,’ he says. ‘The drugs can also cause cognitive impairment, so they might be confused about how many pills they have taken.
GABA drugs are being prescribed in place of benzos or opioids — ‘in the likely mistaken belief they are less liable to misuse or dependence and the lack of awareness of withdrawal problems that can arise’, says the PHE report
‘Having said that, the risks shouldn’t be overstated — the increased risk of suicidal behaviour for instance is 1.2 times higher, not double or treble, and the drugs do work well for some people.’
This reassurance rings hollow for Natalia Buzzeo, 27, a former bar worker from Tyne and Wear, who went on pregabalin after being injured in a car crash in 2012.
She was prescribed 150mg a day in hospital. ‘The GP kept me on them for six years for the pain and even increased the dose,’ says Natalia. ‘No one at any point told me about any side-effects.’
Yet Natalia says almost immediately she felt ‘like a zombie’. ‘I’d always been popular, but my personality changed — I fell out with people, lost friends and eventually my relationship with my boyfriend broke down,’ she says. ‘I’d lie in bed all day and watch TV. The pills worked for the pain, but I couldn’t feel anything emotionally.
‘I also became anxious and depressed, so I went back to my GP after a couple of months. He said it was due to the accident and increased my dose to 300mg.
‘After that I went into a downward spiral of self-destruction, I began self-harming, repeatedly cutting my arms and legs.’
By 2015, three years after the car crash, Natalia’s dose had been increased to 900mg a day.
NHS figures also reveal that prescriptions have rocketed in the past ten years, from one million for pregabalin in 2008 to seven million in 2018; gabapentin prescriptions rose from 1.75 million to 7.3 million over the same period
‘I honestly don’t know why,’ says Natalia, who has little memory of the nine months on that dose.
‘Looking back, it’s a blur, I was completely out of it. My family couldn’t get through to me. I must have made 20 suicide attempts.’
It’s been known for well over a decade that gabapentinoids can make people suicidal, and was made clear in trial data submitted to the Food and Drug Administration, the U.S. drug approval body.
‘But part of the reason it’s gone under the radar is the fact that these effects may not kick in for four to six weeks or longer after starting on them and often even longer, so the connection with the drug isn’t often made,’ says Dr David Healy, a consultant psychiatrist at Bangor University and founder of the drug side-effects website RxISK.org.
Natalia says that her family eventually had to take her to a mental hospital, where she was diagnosed with major depression.
In May 2018 Natalia went to hospital after another minor accident. ‘When I said I was on pregabalin, a doctor said to me: “Do you not know what the drug does to you?” and mentioned the side-effects. I became convinced it was causing my depression.’
So she went cold turkey. ‘I literally felt like my organs would shut down. I was hallucinating and didn’t know what was real and what wasn’t. I now know I should have tapered my dose down gradually.’
She turned to an online support group, Pregabalin Survivors.
‘It’s taken me nine months to fully recover,’ says Natalia.
‘I’m getting my friends and social life back, I get up and go out every day and go to the gym and eventually I want to get back to work.’
Viv Jolly, 59, and Chris, 61, former teachers who live in Yorkshire with their three grandchildren, lost their daughter Sarah, 34, last year to an accidental overdose of pregabalin, prescribed for back pain since 2014
A post-mortem found Sarah had six times her prescribed dose of 150mg a day in her bloodstream, as well as haloperidol, an anti-psychotic for schizophrenia.
Sarah’s case was complicated, but her mother puts the blame for her death on the pregabalin.
‘Sarah had her problems with alcohol and drug addiction, but seemed to be coming out of it all — she hadn’t had a drink for 18 months and was in a good place psychologically,’ says Viv.
‘I think we’re all lulled into the false sense of security that if a GP prescribes something, it must be safe. But they don’t always get it right. Sarah had a spinal problem — maybe she could have had another treatment instead?’
Earlier this year a review by the highly respected Cochrane Database, which looked at more than 40 studies involving 100,000 people, found ‘only low-quality evidence for [pregabalin’s] effectiveness after trauma due to stroke or spinal cord injury’. And, ‘very limited evidence is available for neuropathic back pain, neuropathic cancer pain, and some other forms of neuropathic pain’.
So quite how did GABA drugs, with only a limited evidence base for pain, become so widely prescribed in a short space of time?
‘When these drugs came out [pregabalin in 2004, gabapentin in 1993], they were regarded as real game-changers as they had a new mechanism for treating nerve pain,’ says Dr Stannard.
‘There was a lot of heavy marketing to pain consultants who then prescribed them to patients, and GPs kept patients on them and followed consultants’ leads by prescribing them to others.
‘What we can say is the percentage of cases where they work in real life is much lower than in clinical trials,’ she adds.
Dr Martin Johnson, spokesman for the Royal College of General Practitioners, says that after stringent tests, GABA drugs are appropriate.
He adds: ‘Patients need annual checks as a minimum if they are on a low dose; if they’re at a higher dose, they need to be followed up more frequently.’
Pfizer is adamant gabapentin and pregabalin have ‘always been marketed according to the approved UK product label.’
It says: ‘When prescribed and administered appropriately as per the approved label, gabapentin and pregabalin are important treatment options for many people living with the conditions for which they are approved.
‘The efficacy and safety of these medicines have been demonstrated in a large number of robust clinical trials among thousands of patients in the approved indications.
‘Patient safety is, and will always be, Pfizer’s utmost priority.’