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Where are we now with paracetamol?

BMJ 2015; 351 doi: (Published 10 July 2015) Cite this as: BMJ 2015;351:h3705

Rapid Response:

Does Paracetamol meet Barber's criteria?

James W Dear (10 July 2015; 351:h3705) provides a new and interesting perspective on our habitual prescribing of paracetamol. The article suggests that paracetamol, the most widely prescribed drug, may not be as effective or safe as widely assumed. Whenever prescribing a new drug, the prescriber should try to adhere to Barber’s criteria by maximising effectiveness, minimising risks, minimising costs and respecting the patient’s choices [1].

The first of Barber’s criteria is to be discussed is cost-effectiveness. As J. Dear put, paracetamol is a first-line analgesic, but also an effective anti-pyretic. Hence, a 3p tablet which does not require monitoring nor follow-up and is available over-the-counter fulfils this criteria [2]. Not to add the annual cost of £72 million for paracetamol prescriptions, this is only 14.6% of the budget spent on analgesics.

The alternative drugs for paracetamol depending on their “effectiveness” are NSAIDs, amitriptyline, gabapentin and opioids. NSAIDs are effective for inflammatory pains, however their use is limited to adults and their pharmacoeconomic are not as effective. 1.8% of patients are hospitalised, 6.6% have GI diagnostic tests and 5.5% died. This costs roughly £1 per patient-day for just GI-side effects [3].
On the other hand there are opioids, however opioids have an entourage of adverse effects including: GI and CNS/dizziness. These effects have a direct cost of adjunct medication, anti-emetics and laxatives, and further consultations for adverse effects or non-concordance. The indirect costs include absence from work and less social functioning, which is a major socioeconomic expense [4].

J. Dear reports 673 patients admitted to a UK liver transplantation unit with paracetamol-induced injury [5]. 53 of these 673 Scottish patients from the years 1992 to 2009 had liver transplants secondary to a paracetamol overdose. Since approximately 22 million prescriptions are issued every year and that paracetamol is also available over-the-counter, a Lilliputian number of 4 patients suffering from severe injury from “safe doses” are hardly concerning [2]. In comparison, an alternative analgesic such as an NSAID has a long list of potential adverse reaction including acute kidney injury affecting 1-5% of patients. J. Dear provides an interesting comparison of a study on rodents to the foetus in pregnant women; however, I fail to see the clinical application of comparing two different species with significantly different metabolism.

As J. Dear reminds us, paracetamol may not provide a clinically significant improvement in pain compared to placebo in some instances of musculoskeletal pain, but its superiority to placebo was demonstrated for other forms of pain such as dental pain and headaches. The use of placebo treatments raises many ethical issues, but it could be argued that one of the aims of medicine is to relieve suffering [6]. Furthermore, the efficacy paradox is an important idea missed by many clinicians. The paradox is that there is an overwhelming pressure to ignore certain drug treatment because of a significant placebo response, and choosing alternatives that although may be “significantly” better than their placebo are no better than the first drug [7]. If that is so, is it not justifiable to use low-risk placebo treatments to provide symptomatic relief?

Ultimately, we should find a treatment in alliance with the patient that relieves their symptoms with the least possible side-effects and whose route and frequency of administration is acceptable to the patient.

Although further setting-specific studies may help understand the effectiveness of paracetamol in various clinical situations, what is the alternative, a nation of peptic ulcers?

1. Barber, N. What constitutes good prescribing? The BMJ. 1995;310:923.
2. Health & Social Care Information Centre. Prescriptions dispensed in the community: England 2002-12. UK: HSCIC, 2013.
3. Rahme, E. et al. Cost of prescribed NSAID-related gastrointestinal adverse events in elderly patients. British Journal of Clinical Pharmacology. 2001;52(2);185-192.
4. Annemans, L. Pharmacoeconomic impact of adverse events of long-term opioid treatment for the management of persistent pain. Clinical Drug Investigation. 2011: 31(2):73-86.
5. Bretherick AD, et al. Acute liver failure in Scotland between 1992 and 2009; incidence, aetiology and outcome. Q J Med 2011;104:945-56.
6. Miller FG and Colloca L. The Legitimacy of Placebo Treatments in Clinical Practice: Evidence and Ethics. The American Journal of Bioethics 2009; 9:12, 39-47.
7. Wallach, H. The Efficacy Paradox in Randomized Controlled Trials of CAM and Elsewhere: Beware of the Placebo Trap. Journal of Alternative and Complimentary Medicine. 2001:7:213-218.

Competing interests: No competing interests

14 July 2015
Balraj Bishan Singh Mavi
Medical Student
Sofia Labbouz