BMJ 2015;350:h1225 doi: 10.1136/bmj.h1225
Page 1 of 3
Research
RESEARCH
PICO
Efficacy and safety of paracetamol for spinal pain and
osteoarthritis: systematic review and meta-analysis of
randomised placebo controlled trials
OPEN ACCESS
1
1
2
2
Gustavo C Machado , Chris G Maher , Paulo H Ferreira , Marina B Pinheiro , Chung-Wei Christine
1
34
56
17
Lin , Richard O Day , Andrew J McLachlan , Manuela L Ferreira
The George Institute for Global Health, Sydney Medical School, University of Sydney, Sydney, NSW 2000, Australia; 2Faculty of Health Sciences,
University of Sydney, Sydney, NSW 2141, Australia; 3Department of Clinical Pharmacology, St Vincent’s Hospital and University of New South
Wales, Sydney, NSW 2010, Australia; 4School of Medical Sciences, Department of Medicine, University of New South Wales, Sydney, NSW 2033,
Australia; 5Faculty of Pharmacy, University of Sydney, Sydney, NSW 2050, Australia ; 6Centre for Education and Research on Ageing, Concord
Hospital, Sydney, NSW 2139, Australia; 7Institute of Bone and Joint Research, The Kolling Institute, Sydney Medical School, University of Sydney,
Sydney, NSW 2065, Australia
1
This is a summary of a paper that was published on thebmj.com as BMJ
2015;350:h1225
Abstract
Study question Is paracetamol more effective than placebo in reducing
pain and disability for patients with spinal pain or osteoarthritis?
Summary answer Paracetamol is ineffective in reducing pain or disability
in patients with low back pain and provides small and not clinically
important effects for those with hip or knee osteoarthritis. People taking
paracetamol are also more likely to have abnormal results on liver
function tests.
What is known and what this paper adds Paracetamol is the most
commonly used over-the-counter medicine to treat spinal pain and
osteoarthritis, and clinical guidelines often recommend paracetamol as
the first line analgesic medication for these conditions. Our results
suggest that these recommendations should be reconsidered as
paracetamol seems ineffective in reducing pain and disability or improving
quality of life in patients with low back pain and offers only a small but
not clinically important benefit for pain and disability reduction in patients
with hip or knee osteoarthritis.
Selection criteria for studies
We identified clinical trials that randomly allocated patients
with spinal pain (neck or low back pain) or hip/knee
osteoarthritis to either paracetamol or placebo. An electronic
literature search was conducted without date or language
restrictions, on Medline, Embase, AMED, CINAHL, Web of
Science, LILACS, International Pharmaceutical Abstracts, and
Cochrane Central Register of Controlled Trials from inception
to 8 December 2014. Outcomes of interest were pain, disability,
quality of life, adverse effects, patient adherence, and use of
rescue medication.
Primary outcomes
Our primary outcomes were pain, disability, and quality of life.
Main results and role of chance
We included 12 reports (13 randomised trials), three of which
investigated patients with low back pain and 10 including
patients with osteoarthritis of the hip or knee. For low back pain,
high quality evidence showed no effect of paracetamol on pain
(mean difference –0.5, 95% confidence interval –2.9 to 1.9),
disability (0.4, –1.7 to 2.5), and quality of life (0.4, –0.9 to 1.7)
at short term follow-up (>2 weeks but ≤3 months). For hip or
knee osteoarthritis, high quality evidence showed that
paracetamol provides a small, although not clinically important,
benefit on pain (–3.7, –5.5 to –1.9) and disability (–2.9, –4.9 to
–0.9) in the short term. There was no difference in patient
adherence to treatment (risk ratio 1.0, 95% confidence interval
0.9 to 1.1) and use of rescue medication (0.7, 0.4 to 1.3) between
paracetamol and placebo. The number of patients reporting any
adverse event (1.0, 0.9 to 1.1), any serious adverse event (1.2,
0.7 to 2.1), or withdrawn from the study because of adverse
events (1.2, 0.9 to 1.5) was also similar between the groups.
High quality evidence, however, showed that paracetamol
Correspondence to: G C Machado [email protected]
No commercial reuse: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe
BMJ 2015;350:h1225 doi: 10.1136/bmj.h1225
Page 2 of 3
RESEARCH
increases the risk of having abnormal results on liver function
tests by nearly fourfold (3.8, 1.9 to 7.4), but a link with clinically
important toxicity is still unknown.⇓
Bias, confounding, and other reasons for
caution
None of the trials reported data for long term follow-up, and
our results are limited to the short term efficacy of paracetamol.
Most of the included trials used the maximum dose of 4000
mg/day, as recommended by the US Food and Drug
Administration, with only two trials using 3000 mg/day as the
maximum dose. No individual risk of bias domains (Cochrane
Collaboration’s tool) had a significant influence on our estimated
treatment effects. Also, publication bias (small study effects)
was not identified.
No commercial reuse: See rights and reprints http://www.bmj.com/permissions
Study funding/potential competing
interests
This research received no specific grant from any funding
agency in the public, commercial, or not-for-profit sectors. AJM
received support from GlaxoSmithKline for a PhD scholarship,
and AJM, ROD, CGM, and CCL received support from
GlaxoSmithKline for the PACE trial.
Cite this as: BMJ 2015;350:h1225
This is an Open Access article distributed in accordance with the Creative Commons
Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute,
remix, adapt, build upon this work non-commercially, and license their derivative works
on different terms, provided the original work is properly cited and the use is
non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Subscribe: http://www.bmj.com/subscribe
BMJ 2015;350:h1225 doi: 10.1136/bmj.h1225
Page 3 of 3
RESEARCH
Table
Table 1| Effects of paracetamol on pain and disability outcomes measured on a 0-100 scale
No of trials No of patients Mean difference (95% CI) Quality of evidence
Pain (short term)
Spinal pain
1
1592
–0.5 (–2.9 to 1.9)
High
Osteoarthritis
7
2355
–3.7 (–5.5 to –1.9)
High
Disability (short term)
Spinal pain
1
1522
0.4 (–1.7 to 2.5)
High
Osteoarthritis
7
2354
–2.9 (–4.9 to –0.9)
High
No commercial reuse: See rights and reprints http://www.bmj.com/permissions
Subscribe: http://www.bmj.com/subscribe