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

Abstract

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any adverse event (risk ratio 1.0, 95% confidence interval 0.9 to 1.1), any serious adverse event (1.2, 0.7 to 2.1), or withdrawn from the study because of adverse events (1.2, 0.9 to 1.5) was similar in the paracetamol and placebo groups.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.

Fig 1 Flow chart of trials investigating efficacy of paracetamol in spinal pain and osteoarthritis. Numbers of records from each database include duplicates. IPA=International Pharmaceuticals Abstracts, CENTRAL=Cochrane Register of Controlled Trials

Fig 2 Risk of bias summary showing review authors’ judgments about each risk of bias domain in placebo controlled trials on efficacy of paracetamol for spinal pain and osteoarthritis. Randomised clinical trials are listed alphabetically by author name

Fig 3 Weighted mean differences for pain and disability in placebo controlled trials on efficacy of paracetamol for spinal pain and hip or knee osteoarthritis. Pain and disability are expressed on scale of 0-100. Immediate term=follow-up ≤2 weeks; short term=follow-up evaluations >2 weeks but ≤3 months. Studies ordered chronologically within subgroups

Fig 4 Risk ratio for safety outcome measures, patient adherence, and use of rescue medication in placebo controlled trials on efficacy of paracetamol compared with placebo. Any=No of patients reporting any adverse event; serious=No of patients reporting any serious adverse event (as defined by each study); withdrawals=No of patients withdrawn from study because of adverse events; liver=No of patients with abnormal results on liver function tests. Studies are ordered chronologically within subgroups