In praise of paracetamol
Reproduced from Issue 137 of Arthritis Today
It’s been around so long it’s unappreciated, under-valued and taken for granted. But as the list of known undesirable side-effects from NSAIDs and Cox-2s continues to mount, is paracetamol set to return as the arthritis patient’s painkiller of choice?
Because there is no “magic pill” to slow down or even stop the progression of osteoarthritis, many sufferers are desperate to find something that effectively takes the pain away – and which doesn’t have unpalatable side effects.
For a long time, that something was non-steroidal anti-inflammatory drugs (NSAIDs). More recently the much-vaunted COX-2 inhibitors were hailed in some quarters as the answer to everyone’s prayers. Well, we know what happened to Vioxx, and research now seems to indicate that NSAIDs - despite being effective in relieving pain in both osteoarthritis and rheumatoid arthritis - can also increase the risk of heart attack and stroke in some patients – on top of the already accepted and deeply unpleasant side-effects of stomach ulceration and bleeding.
Prescribing an effective painkiller without side-effects for their arthritis patients is now a serious challenge for family doctors. Many still prescribe NSAIDs in patients at low risk of cardio-vascular disease; fewer now hand out prescriptions for COX-2s. Co-proxamol is being phased out, much to the disgust of those who find it offers them effective pain relief. Mild opiates such as codeine and tramadol offer some options, and opiate skin patches are currently being heavily marketed to GPs. None of these are ideal, however. Codeine can cause severe constipation while opiates can lead to drug dependency.
So where does that leave paracetamol? Used as an analgesic for the past 30 years, long accepted as an effective treatment for the relief of pain and fever in adults and children, and used as a major ingredient in numerous cold and flu medications, it tends to be dismissed as insufficiently effective for the treatment of severe osteoarthritis. However, many clinicians believe that most patients don’t use the drug on a frequent enough basis to enjoy the benefits.
“One of the main problems with paracetamol is that to get the best pain relief people have to take eight tablets– two four times a day – and they don’t like taking that many pills, compared to taking just one NSAID,” explains Dr Philip Helliwell, a consultant rheumatologist in Bradford, and Arthritis Today’s resident doctor.
“So they then don’t take enough paracetamol for it to be effective – and then say it doesn’t work and stop taking it. But it does work, it’s cheap and it’s relatively safe.”
Dr Anita Campbell, a GP in Sheffield, who rarely prescribes NSAIDs to her arthritis patients, and always gives out paracetamol as a first-line painkiller, agrees that one of the drawbacks is its short duration of action, and the need to take it four times a day to maintain effect.
She is among many doctors who would welcome a slow-release form of paracetamol, or its development as a skin patch similar to currently available NSAIDS. But as no one pharmaceutical company owns the patent to paracetamol, there is no profit to be made from its manufacture and therefore little interest in doing it.
“Many clinicians believe that most patients don’t use the drug on a frequent enough basis to enjoy the benefits.”
Phil Conaghan
“Little research has been done on how to use paracetamol in an optimal way, and partly this is due to the fact that the drug is available generically, and there’s no major pharmaceutical investment in it,” explains Phil Conaghan, Professor of Musculoskeletal Medicine at the University of Leeds. “Osteoarthritis research has not been a major priority for many funders although arc is now taking steps to address this.
“However the fact that its effects don’t last long means that people can tailor their medication to their particular symptoms. For people who only get pain during the day it’s clearly not worth using painkillers at night. For many people with osteoarthritis their pain is worse with prolonged walking or standing and therefore their symptoms are often worse in the second half of the day. It may be that using paracetamol tablets starting mid to late morning may be worthwhile. It may also be useful to consider taking two tablets before starting something that is known to bring on the pain, for example a shopping trip or long walk.”
Howard Bird, Professor of Pharmacological Rheumatology at the University of Leeds, believes that another factor that mitigates against the more widespread use of paracetamol is that by the time the average osteoarthritis patient eventually reaches a hospital consultant he or she is likely to have end-stage disease with severe joint pain, which is unlikely to respond to a mild analgesic such as paracetamol alone.
“At this point, the so-called compound generic analgesics notably Co-proxamol (until its recent controversial withdrawal) Co-codamol and Co-dydramol are more likely to be needed,” says Professor Bird.
Michael Doherty
Professor Michael Doherty, a consultant rheumatologist at the University of Nottingham, is a long-time advocate of paracetamol. He believes that NSAIDs have been over-used, and their side-effects (they are estimated to cause around 2,000 deaths a year in the UK) underplayed. “It is described in most doctors’ guidelines as the Number 1 recommended oral painkiller to be tried first by people in pain, and its big bonus is its safety,” he says. “Each year there are more deaths from NSAID-related gut bleeding and perforation than deaths from cancer of the cervix or asthma.”
He believes that the drug’s short duration of action is, in fact, a positive. “The fact that it wears off quickly is a good thing, actually. When a drug is slow-release it stays in the blood stream for days, with more possible side-effects. In my knee osteoarthritis clinic people don’t have a problem taking paracetamol two or three times a day if they are in pain – pain being a great incentive to take tablets!”
“Paracetamol is the first-line choice of painkiller for mild to moderate osteoarthritis.”
The other great drawback of paracetamol is that because it is so readily available it is often used in suicide attempts. For this reason the drug can now only be bought in packets of ten. The safe maximum dose is eight tablets over 24 hours. Twenty taken at one go is an overdose and can cause serious liver damage. Acknowledges Mike Doherty: “It’s a hard message that eight tablets a day is safe but that 20 tablets can kill you.”
Nevertheless its safety when taken at normal doses is very high and side-effects are minimal. It doesn’t irritate the stomach lining as NSAIDs do, and its analgesic properties are well-known and accepted. It remains the first-line choice of painkiller for mild to moderate osteoarthritis because of this safety aspect, although it does not reduce pain as well as NSAIDS in head to head trials. An arc-funded meta-analysis of clinical trials into osteoarthritis, published in the British Medical Journal in 2004, found that NSAIDs offered better pain relief, but that paracetamol was better tolerated and had fewer side-effects.
“It is therefore most commonly used by osteoarthritis patients at the early stages of their condition, before they go to their GP,” says Dr Major Artus, a GP and part-time arc Primary Care Fellow in Stoke. “By the time they go to their GP their symptoms are usually beyond the benefits of paracetamol, and so the doctor then moves on to stronger analgesia. However, I, and I expect other doctors, too, do suggest to patients with osteoarthritis to always use paracetamol whenever they feel it would be sufficient for their symptoms, not the least to reduce their NSAID use.”
Howard Bird believes that paracetamol in combination with other ingredients can offer good pain relief. “Despite the fact that Co-proxamol was the most effective of the three in causing death when used in a suicide attempt, it was also ironically the best of the three in alleviating the symptoms of osteoarthritis, probably because of the slight euphoric lift provide by the dextropropoxyphene component that accompanied the paracetamol, not found in Co-codamol (where the codeine that accompanies the paracetamol can cause depression and constipation) or Co-dydramol (where the dihydrocodeine used with the paracetamol can cause a variety of central nervous system side-effects). So in a sense improving paracetamol has already been attempted by using it in such combinations. Co-codamol and Co-dydramol bear testimony to this and are still widely used.”
Osteoarthritis experts agree that popping painkillers should not be the only way of coping with the condition, pointing to the importance of muscle-strengthening exercises, losing weight, physiotherapy, and exercise as crucial. As Mike Doherty points out: “There is no easy fix for osteoarthritis and in the long-term, lifestyle modifications are important. Tablets are never the answer; they are an adjunct.”
