GPs’ options for managing persistent pain in their patients have declined markedly over the past decade, but it seems we may have finally reached crisis point.
After the rise and fall of co-proxamol, selective COX-2 inhibitors and traditional NSAIDs, the last thing GPs needed was to see the safety of yet another analgesic called into question, especially the one most often prescribed.
So last month’s unexpected announcement from NICE that its advisers were ‘extremely concerned’ over evidence of side-effects with paracetamol, and that it would be recommending against its use in new osteoarthritis guidance, was greeted with dismay.
‘So what exactly is left?’ asked one GP on PulseToday after the news broke. ‘Rx: 1 hug and cup of tea,’ suggested another.
And they aren’t alone, with many GPs wondering just what they can recommend to patients with osteoarthritis, fibromyalgia or back pain.
As other drugs have been restricted on safety grounds, GPs have become increasingly reliant on paracetamol to manage chronic pain, with NHS prescriptions more than doubling since 2004.
GPs had already been forced to turn back to traditional NSAIDs, after the dramatic demise of selective COX-2 inhibitors (coxibs) due to concerns
over increased risk of cardiovascular complications.
But since the warning to stop using coxibs from the Medicines and Healthcare Products Regulatory Agency (MHRA) in 2004, evidence has emerged of cardiovascular and renal complications with non-selective NSAIDs, particularly diclofenac and high-dose ibuprofen.
Some of these risks can be reduced by switching patients to from diclenofac to naproxen, also reflected in GP prescribing trends (see graph below).
On top of this, GPs have been boxed in further by concerns over rising opioid prescribing, the withdrawal of co-proxamol in 2009 and increasingly draconian restrictions on referrals for joint replacement surgery.
It was against this background that NICE issued its draft guidance last month recommending that paracetamol should not be routinely offered in osteoarthritis, and used at only the ‘lowest effective dose’ for the ‘shortest possible time’.
‘Risks outweigh gains’
NICE says it is ‘extremely concerned’ about observational data that show an increased risk of cardiovascular, gastrointestinal and renal adverse events with paracetamol use.
Although it admits that the drug has been viewed as a ‘cheap, effective way of managing pain’, its analysis of the evidence shows a ‘lack of efficacy’ and that ‘on balance, the risks of paracetamol outweigh the benefits of any gain in symptom control’.
The draft guidance also warns against prescribing paracetamol in combination with an oral NSAID, and urges GPs to ask patients about their use of over-the counter medicines to ensure they are not taking large doses of paracetamol and NSAIDs.
The advice is based on a NICE analysis of data from a UK study of 1.2m general practice records in 2010 that found a 28% increase in mortality with paracetamol and a 50% increase when used in combination with ibuprofen alone, compared with those not using the drugs. There was a 12% increase in the ibuprofen-only group.
The same study showed a 36% increase in the risk of upper gastrointestinal events and a 20% increase in renal failure with paracetamol use alone.
But GPs have criticised the guideline for not looking at opioid-paracetamol combinations, such as co-codamol, and NICE’s analysis has been contradicted by the MHRA, which says it can see no new evidence that would change the risk-benefit balance for paracetamol.
Dr Dermot Ryan, a GP in Loughborough and honorary research fellow at University of Edinburgh, says the advice to rule out paracetamol for osteoarthritis would have wide-ranging implications.
He says: ‘For some people it’s very beneficial. And what will happen here is some people will say, “NICE says you can’t use paracetamol” and they will just put a blanket stop on using it.
‘Where do you go next? You go to the opioids, so then patients get constipation so they need lactocellulose, or they get faecal impaction and sometimes need to go into hospital because of an obstruction.
‘And sometimes the opioids affect them mentally, making them sleepy all the time or confused. So you end up asking which is worse – paracetamol or opioids?’
Dr Ryan reasons that patients are often willing to accept the risks associated with a treatment if they feel it benefits them, after discussion of the pros and cons.
He says: ‘It is similar to the pronouncements on naproxen and diclofenac. The reality is that when you change patients from diclofenac to naproxen – I’ve done it with a number of patients following the ruling not to use it because of heart and renal risks – the patients are back in two weeks wanting their diclofenac back because they find naproxen doesn’t work. Whether that’s real or psychological, the fact is the patients are willing to accept those risks.’
Dr Bill Beeby, the GPC’s prescribing subcommittee chair and a GP in Middlesbrough, confesses he is ‘struggling’ with the reasoning behind the draft guidance, ‘much as my patients will be, if I recommend the use of “the lowest possible dose” of paracetamol “for the shortest possible time”.’
He adds: ‘This is a guarantee of treatment failure and, since the psychology of the healing power of doctors often requires the use of a token in the form of a prescription, it may well lead to less desirable medications being used.’
But Dr John Dickson, a community rheumatologist and another GP in Middlesbrough, says the concern over gastrointestinal bleeding is valid, particularly in elderly people, although he says NICE should also have considered the impact of combination drugs such as co-codamol.
He explains: ‘GI bleeding is a common problem but it’s not being recognised. It’s the elderly I worry about – if you drop a gramme of haemoglobin, that gives you a lot less energy and if you’re living alone and you’re feeling tired, your mental function is not good.’
Professor Martin Underwood, professor of primary care at the University of Warwick, says approval of the draft guidance by NICE could represent an ‘important change in practice’.
He says: ‘It does have the potential to make a major change to how we practise. What this will mean, given that we also know anti-inflammatory drugs have a high incidence of adverse events and we wouldn’t be too keen on regular use of opioids, is that we are getting quite limited in the choice of drugs we can use.
‘There will need to be alternative treatment regimens available, which will be more around help with losing weight and increasing physical activity, and these types of things. So the NICE guidance, when it finally comes out, needs to be treated as a package.’
Professor Underwood says the important thing is for CCGs to be ‘tooling themselves up’ to deliver alternative interventions and ‘move away from just giving pills’.
Change of focus
Dr Tom Margham, primary care lead for Arthritis Research UK and a GP in east London, says the upside to limiting analgesic options is that it may lead to a better focus on alternative treatments.
He says: ‘This forces clinicians to look a bit more broadly at other options: the topical NSAIDs, things like topical capsaicin and the benefits of things like aerobic exercise, muscle strengthening and stretching, use of assistive devices such as walking sticks and aids for walking, bracing and corrective footwear.
‘For example, with a knee that is unstable, the use of a brace or other support can significantly correct the biomechanical problem, helping to align the joint properly so it works better, preventing painful flare-ups.’ The NICE consultation on the guidance runs until October.
The evidence against paracetamol use:
US study shows use of NSAIDs or paracetamol at high frequency or dose is associated with a significantly increased risk of major cardiovascular events.
UK study of 1.2m general practice records in 2010 finds a 28% increase in mortality with paracetamol and a 50% increase when used in combination with ibuprofen alone, compared with those not using the drugs. It also shows a 12% increase in the ibuprofen group. The study also identifies a 36% increase in the risk of upper gastrointestinal events, a 14% increase in heart attack risk and a 20% increase in renal failure risk with paracetamol use.
Br J Clin Pharmacol 2010;70:429-38
An Osteoarthritis Research Society International review of evidence for various analgesics in osteoarthritis concludes there is accumulating evidence to suggest high-dose paracetamol may have upper gastrointestinal side-effects. It also finds ‘some evidence’ to suggest mild loss of renal function in women following long-term consumption of high doses.
Osteo Carti 2010;18:476-99
University of Nottingham researchers show an increased risk of a fall in haemoglobin after 13 weeks’ treatment with ibuprofen or paracetamol alone, with the risk doubling when the drugs are taken in combination.
Ann Rheum Dis 2011;70:1534-41