. 2023 Mar 22:380:e072962.

doi: 10.1136/bmj-2022-072962.

Comparative effectiveness and safety of analgesic medicines for adults with acute non-specific low back pain: systematic review and network meta-analysis

Michael A Wewege^{1

2}, Matthew K Bagg^{2

3

4}, Matthew D Jones^{1

2}, Michael C Ferraro^{1

2}, Aidan G Cashin^{1

2}, Rodrigo Rn Rizzo^{1

2}, Hayley B Leake^{2

5}, Amanda D Hagstrom¹, Saurab Sharma^{1

2}, Andrew J McLachlan⁶, Christopher G Maher^{7

8}, Richard Day^{9

10}, Benedict M Wand¹¹, Neil E O'Connell¹², Adriani Nikolakopolou¹³, Siobhan Schabrun^{2

14

15}, Sylvia M Gustin^{2

16}, James H McAuley^{17

2}

Affiliations

¹ School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
² Centre for Pain IMPACT, Neuroscience Research Australia, Sydney, NSW, Australia.
³ Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Perth, WA, Australia.
⁴ Perron Institute for Neurological and Translational Science, Perth, WA, Australia.
⁵ IIMPACT in Health, University of South Australia, Adelaide, SA, Australia.
⁶ Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Gadigal Country, Sydney, NSW, Australia.
⁷ Sydney Musculoskeletal Health, University of Sydney, Gadigal Country, Sydney, NSW, Australia.
⁸ Institute for Musculoskeletal Health, Sydney Local Health District, Sydney, NSW, Australia.
⁹ Clinical Pharmacology and Toxicology, St Vincent's Hospital, Sydney, NSW, Australia.
¹⁰ St Vincent's Clinical School, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
¹¹ Faculty of Medicine, Nursing and Midwifery and Health Sciences, University of Notre Dame Australia, Fremantle, WA, Australia.
¹² Department of Health Sciences, Centre for Health and Wellbeing Across the Lifecourse, Brunel University London, Uxbridge, UK.
¹³ Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Centre, University of Freiburg, Freiburg, Germany.
¹⁴ School of Physical Therapy, University of Western Ontario, London, ON, Canada.
¹⁵ The Gray Centre for Mobility and Activity, Parkwood Institute, London, ON, Canada.
¹⁶ NeuroRecovery Research Hub, School of Psychology, University of New South Wales, Sydney, NSW, Australia.
¹⁷ School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia j.mcauley@neura.edu.au.

PMID: 36948512
PMCID: PMC10540836
DOI: 10.1136/bmj-2022-072962

Comparative effectiveness and safety of analgesic medicines for adults with acute non-specific low back pain: systematic review and network meta-analysis

Michael A Wewege et al. BMJ. 2023.

. 2023 Mar 22:380:e072962.

doi: 10.1136/bmj-2022-072962.

Authors

Affiliations

¹ School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
² Centre for Pain IMPACT, Neuroscience Research Australia, Sydney, NSW, Australia.
³ Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Perth, WA, Australia.
⁴ Perron Institute for Neurological and Translational Science, Perth, WA, Australia.
⁵ IIMPACT in Health, University of South Australia, Adelaide, SA, Australia.
⁶ Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Gadigal Country, Sydney, NSW, Australia.
⁷ Sydney Musculoskeletal Health, University of Sydney, Gadigal Country, Sydney, NSW, Australia.
⁸ Institute for Musculoskeletal Health, Sydney Local Health District, Sydney, NSW, Australia.
⁹ Clinical Pharmacology and Toxicology, St Vincent's Hospital, Sydney, NSW, Australia.
¹⁰ St Vincent's Clinical School, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.
¹¹ Faculty of Medicine, Nursing and Midwifery and Health Sciences, University of Notre Dame Australia, Fremantle, WA, Australia.
¹² Department of Health Sciences, Centre for Health and Wellbeing Across the Lifecourse, Brunel University London, Uxbridge, UK.
¹³ Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Centre, University of Freiburg, Freiburg, Germany.
¹⁴ School of Physical Therapy, University of Western Ontario, London, ON, Canada.
¹⁵ The Gray Centre for Mobility and Activity, Parkwood Institute, London, ON, Canada.
¹⁶ NeuroRecovery Research Hub, School of Psychology, University of New South Wales, Sydney, NSW, Australia.
¹⁷ School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia j.mcauley@neura.edu.au.

PMID: 36948512
PMCID: PMC10540836
DOI: 10.1136/bmj-2022-072962

Abstract

Objective: To evaluate the comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain.

Design: Systematic review and network meta-analysis.

Data sources: Medline, PubMed, Embase, CINAHL, CENTRAL, ClinicalTrials.gov, clinicialtrialsregister.eu, and World Health Organization's International Clinical Trials Registry Platform from database inception to 20 February 2022.

Eligibility criteria for study selection: Randomised controlled trials of analgesic medicines (eg, non-steroidal anti-inflammatory drugs, paracetamol, opioids, anti-convulsant drugs, skeletal muscle relaxants, or corticosteroids) compared with another analgesic medicine, placebo, or no treatment. Adults (≥18 years) who reported acute non-specific low back pain (for less than six weeks).

Data extraction and synthesis: Primary outcomes were low back pain intensity (0-100 scale) at end of treatment and safety (number of participants who reported any adverse event during treatment). Secondary outcomes were low back specific function, serious adverse events, and discontinuation from treatment. Two reviewers independently identified studies, extracted data, and assessed risk of bias. A random effects network meta-analysis was done and confidence was evaluated by the Confidence in Network Meta-Analysis method.

Results: 98 randomised controlled trials (15 134 participants, 49% women) included 69 different medicines or combinations. Low or very low confidence was noted in evidence for reduced pain intensity after treatment with tolperisone (mean difference -26.1 (95% confidence intervals -34.0 to -18.2)), aceclofenac plus tizanidine (-26.1 (-38.5 to -13.6)), pregabalin (-24.7 (-34.6 to -14.7)), and 14 other medicines compared with placebo. Low or very low confidence was noted for no difference between the effects of several of these medicines. Increased adverse events had moderate to very low confidence with tramadol (risk ratio 2.6 (95% confidence interval 1.5 to 4.5)), paracetamol plus sustained release tramadol (2.4 (1.5 to 3.8)), baclofen (2.3 (1.5 to 3.4)), and paracetamol plus tramadol (2.1 (1.3 to 3.4)) compared with placebo. These medicines could increase the risk of adverse events compared with other medicines with moderate to low confidence. Moderate to low confidence was also noted for secondary outcomes and secondary analysis of medicine classes.

Conclusions: The comparative effectiveness and safety of analgesic medicines for acute non-specific low back pain are uncertain. Until higher quality randomised controlled trials of head-to-head comparisons are published, clinicians and patients are recommended to take a cautious approach to manage acute non-specific low back pain with analgesic medicines.

Systematic review registration: PROSPERO CRD42019145257.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: this study received project support funding from a 2020 Exercise Physiology Research (Consumables) Grant from the University of New South Wales, which was used to obtain translations of studies published in languages other than English. MKB received travel support from Memorial University of Newfoundland to speak about engagement with research evidence, including the effects of medicines. The Sydney Pharmacy School receives funding from GlaxoSmithKline for a postgraduate scholarship supporting a research student supervised by AJM; all other authors declare no competing interests.

Figures

**Fig 1**
Flow diagram of study identification, screening, and inclusion

**Fig 2**
Network plot for pain intensity for medicines for placebo network. Within each network, the node size is proportional to the sample size of each intervention and the line thickness is proportional to the number of trials in the comparison (also indicated by the numbers). Light purple shading indicates trials with more than two arms. The two trials that did not connect to the network and that were not included were hydrocodone plus ibuprofen versus oxycodone plus paracetamol (Palangio 2002; for full details of references see supplement 2); and etodolac plus thiocolchicoside versus etodolac plus tolperisone (Garg 2019)

**Fig 3**
Naproxen network plot for pain intensity for medicines. Within each network, the node size is proportional to the sample size of each intervention and the line thickness is proportional to the number of trials in the comparison (also indicated by the numbers). Light purple shading indicates trials with more than two arms

**Fig 4**
Forest plot for analgesic medicines and pain intensity. Medicines are ordered according to their P score ranking and compared with placebo. Point estimates refer to the mean difference. The bars indicate 95% confidence interval. Direct comparisons refer to the number of included studies comparing the intervention to placebo. Random effects model: τ²=11.51. CI=confidence interval; SR=sustained release

**Fig 5**
Network plot for safety for medicines. The node size in proportional the sample size of each intervention. The line thickness is proportional the number of trials in the comparison (also indicated by the numbers). Light blue shading indicates trials with more than two arms. The two trials that did not connect to the network and were not included were hydrocodone plus ibuprofen versus oxycodone plus paracetamol (Palangio 2002; for full details of references see supplement 2); and etodolac plus thiocolchicoside versus etodolac plus tolperisone (Garg 2019)

**Fig 6**
Forest plot for analgesic medicines with safety (any adverse event). Medicines are ordered according to their P score ranking and compared with placebo. Point estimates refer to the risk ratio. The bars indicate the 95% confidence interval. Direct comparisons refer to the number of included studies comparing the intervention to placebo. Random effects model: τ²=0.015.CI=confidence interval; SR=sustained release

**Fig 7**
Forest plot for analgesic medicine classes with pain intensity. Medicine classes are ordered according to their P score ranking and compared with placebo. Point estimates refer to the mean difference. The bars indicate 95% confidence interval. Direct comparisons refer to the number of included studies comparing the intervention to placebo. Random effects model: τ²=23.93. CI=confidence interval; COX-2=cyclooxygenase 2; NSAIDs=non-steroidal anti-inflammatory drugs

See this image and copyright information in PMC

References

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Comparative effectiveness and safety of analgesic medicines for adults with acute non-specific low back pain: systematic review and network meta-analysis

Affiliations

Comparative effectiveness and safety of analgesic medicines for adults with acute non-specific low back pain: systematic review and network meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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