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Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials

BMJ 2015; 350 doi: (Published 31 March 2015) Cite this as: BMJ 2015;350:h1225
  1. Gustavo C Machado, PhD student1,
  2. Chris G Maher, director1,
  3. Paulo H Ferreira, senior lecturer2,
  4. Marina B Pinheiro, PhD student2,
  5. Chung-Wei Christine Lin, associate professor1,
  6. Richard O Day, professor34,
  7. Andrew J McLachlan, professor56,
  8. Manuela L Ferreira, associate professor17
  1. 1The George Institute for Global Health, Sydney Medical School, University of Sydney, Sydney, NSW 2000, Australia
  2. 2Faculty of Health Sciences, University of Sydney, Sydney, NSW 2141, Australia
  3. 3Department of Clinical Pharmacology, St Vincent’s Hospital and University of New South Wales, Sydney, NSW 2010, Australia
  4. 4School of Medical Sciences, Department of Medicine, University of New South Wales, Sydney, NSW 2033, Australia
  5. 5Faculty of Pharmacy, University of Sydney, Sydney, NSW 2050, Australia
  6. 6Centre for Education and Research on Ageing, Concord Hospital, Sydney, NSW 2139, Australia
  7. 7Institute of Bone and Joint Research, The Kolling Institute, Sydney Medical School, University of Sydney, Sydney, NSW 2065, Australia
  1. Correspondence to: G C Machado gmachado{at}
  • Accepted 4 February 2015


Objective To investigate the efficacy and safety of paracetamol (acetaminophen) in the management of spinal pain and osteoarthritis of the hip or knee.

Design Systematic review and meta-analysis.

Data sources Medline, Embase, AMED, CINAHL, Web of Science, LILACS, International Pharmaceutical Abstracts, and Cochrane Central Register of Controlled Trials from inception to December 2014.

Eligibility criteria for selecting studies Randomised controlled trials comparing the efficacy and safety of paracetamol with placebo for spinal pain (neck or low back pain) and osteoarthritis of the hip or knee.

Data extraction Two independent reviewers extracted data on pain, disability, and quality of life. Secondary outcomes were adverse effects, patient adherence, and use of rescue medication. Pain and disability scores were converted to a scale of 0 (no pain or disability) to 100 (worst possible pain or disability). We calculated weighted mean differences or risk ratios and 95% confidence intervals using a random effects model. The Cochrane Collaboration’s tool was used for assessing risk of bias, and the GRADE approach was used to evaluate the quality of evidence and summarise conclusions.

Results 12 reports (13 randomised trials) were included. There was “high quality” evidence that paracetamol is ineffective for reducing pain intensity (weighted mean difference −0.5, 95% confidence interval −2.9 to 1.9) and disability (0.4, −1.7 to 2.5) or improving quality of life (0.4, −0.9 to 1.7) in the short term in people with low back pain. For hip or knee osteoarthritis there was “high quality” evidence that paracetamol provides a significant, although not clinically important, effect on pain (−3.7, −5.5 to −1.9) and disability (−2.9, −4.9 to −0.9) in the short term. The number of patients reporting any adverse event (risk ratio 1.0, 95% confidence interval 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 similar in the paracetamol and placebo groups. Patient adherence to treatment (1.0, 0.9 to 1.1) and use of rescue medication (0.7, 0.4 to 1.3) was also similar between groups. “High quality” evidence showed that patients taking paracetamol are nearly four times more likely to have abnormal results on liver function tests (3.8, 1.9 to 7.4), but the clinical importance of this effect is uncertain.

Conclusions Paracetamol is ineffective in the treatment of low back pain and provides minimal short term benefit for people with osteoarthritis. These results support the reconsideration of recommendations to use paracetamol for patients with low back pain and osteoarthritis of the hip or knee in clinical practice guidelines.

Systematic review registration PROSPERO registration number CRD42013006367.


  • Contributors: GCM, MLF, CGM, PHF, C-WCL, ROD, and AJMcL were involved in the conception and design of the review. GCM, MLF, and MBP developed the search strategy and performed study selection. GCM and MBP extracted data from included studies. GCM and MLF were involved in the data analysis. GCM, MLF, CGM, PHF, C-WCL, ROD, and AJMcL were involved in the interpretation and discussion of results. GCM drafted the manuscript, and MLF, CGM, and PHF contributed to the drafting of the review. CCL, ROD, MBP, and AJMcL revised it critically for important intellectual content. All authors approved the final version of the article. All authors had access to all of the data in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. MLF is guarantor.

  • Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. GCM and MBP hold an international postgraduate research scholarship/postgraduate award from the Australian Government. CGM is supported by research fellowship from the National Health and Medical Research Council. MLF holds a fellowship from Sydney Medical Foundation/Sydney Medical School. CCL holds a career development fellowship from the National Health and Medical Research Council, Australia. RD is a chief investigator on NH&MRC Programme Grant No 1054146. AJM is an investigator on the NHMRC Centre for Research Excellence in Medicines and Ageing.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: AJM received support from GlaxoSmithKline for a PhD scholarship, and AJM, ROD, CGM, and C-WCL received support from GlaxoSmithKline for the PACE trial.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

  • Transparency: The lead author (GCM) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; no important aspects of the study have been omitted.

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