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Meta-Analysis
. 2024 Aug;84(8):953-967.
doi: 10.1007/s40265-024-02065-w. Epub 2024 Jun 28.

Paracetamol Combination Therapy for Back Pain and Osteoarthritis: A Systematic Review and Meta-Analyses

Zhiying Cao  1 , Kaiyue Han  1 , Hanting Lu  1 , Sandalika Illangamudalige  1 , Christina Abdel Shaheed  2   3 , Lingxiao Chen  4   5 , Andrew J McLachlan  6 , Asad E Patanwala  6   7 , Christopher G Maher  2   3 , Chung-Wei Christine Lin  2   3 , Lyn March  8   9 , Manuela L Ferreira  3   9 , Stephanie Mathieson  10   11
Affiliations
Meta-Analysis

Paracetamol Combination Therapy for Back Pain and Osteoarthritis: A Systematic Review and Meta-Analyses

Zhiying Cao et al. Drugs. 2024 Aug.

Abstract

Background and objective: Although paracetamol (acetaminophen) combined with other analgesics can reduce pain intensity in some pain conditions, its effectiveness in managing low back pain and osteoarthritis is unclear. This systematic review investigated whether paracetamol combination therapy is more effective and safer than monotherapy or placebo in low back pain and osteoarthritis.

Methods: Online database searches were conducted for randomised trials that evaluated paracetamol combined with another analgesic compared to a placebo or the non-paracetamol ingredient in the combination (monotherapy) in low back pain and osteoarthritis. The primary outcome was a change in pain. Secondary outcomes were (serious) adverse events, changes in disability and quality of life. Follow-up was immediate (≤ 2 weeks), short (> 2 weeks but ≤ 3 months), intermediate (> 3 months but < 12 months) or long term (≥ 12 months). A random-effects meta-analysis was conducted. Risk of bias was assessed using the original Cochrane tool, and quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

Results: Twenty-two studies were included. Pain was reduced with oral paracetamol plus a non-steroidal anti-inflammatory drug (NSAID) at immediate term in low back pain (paracetamol plus ibuprofen vs ibuprofen [mean difference (MD) - 6.2, 95% confidence interval (CI) -10.4 to -2.0, moderate evidence]) and in osteoarthritis (paracetamol plus aceclofenac vs aceclofenac [MD - 4.7, 95% CI - 8.3 to - 1.2, moderate certainty evidence] and paracetamol plus etodolac vs etodolac [MD - 15.1, 95% CI - 18.5 to - 11.8; moderate certainty evidence]). Paracetamol plus oral tramadol reduced pain compared with placebo at intermediate term for low back pain (MD - 11.7, 95% CI - 19.2 to - 4.3; very low certainty evidence) and osteoarthritis (MD - 6.8, 95% CI - 12.7 to -0.9; moderate certainty evidence). Disability scores improved in half the comparisons. Quality of life was infrequently measured. All paracetamol plus NSAID combinations did not increase the risk of adverse events compared to NSAID monotherapy.

Conclusions: Low-to-moderate quality evidence supports the oral use of some paracetamol plus NSAID combinations for short-term pain relief with no increased risk of harm for low back pain and osteoarthritis compared to its non-paracetamol monotherapy comparator.

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Conflict of interest statement

Zhiying Cao, Kaiyue Han, Hanting Lu, Sandalika Illangamudalige, Christina Abdel Shaheed, Lingxiao Chen, Asad E Patanwala, Christopher G Maher, Chung-Wei Christine Lin, Lyn March and Stephanie Mathieson have no conflicts of interest that are directly relevant to the content of this article. Andrew J. McLachlan has provided education services sponsored by Bayer and Haleon. The Sydney Pharmacy School receives research funding from GSK for a scholarship supervised by Andrew J. McLachlan. Manuela L. Ferreira and Andrew J. McLachlan serve on an advisory board for Viatris related to celecoxib use in primary care.

Figures

Fig. 1
Fig. 1
PRISMA (preferred reporting items for systematic reviews and meta-analyses) flow chart. WHO ICTRP World Health Organization International Clinical Trials Registry Platform
Fig. 2
Fig. 2
Risk of bias scores
Fig. 3
Fig. 3
Pain outcome forest plot. CI confidence interval, OA osteoarthritis, LBP low back pain, SD standard deviation
Fig. 4
Fig. 4
Adverse event forest plot. CI confidence interval, ER extended release, M-H Mantel-Haenszel, OA osteoarthritis, LBP low back pain
See this image and copyright information in PMC

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