Papers

Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: a systematic review

^a Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, PO Box 22700, NL-1100 DE Amsterdam, Netherlands, ^b Department of Epidemiology, University of Limburg, PO Box 616, NL-6200 MD Maastricht, Netherlands, ^c Department of Anaesthesiology, Academic Medical Centre, University of Amsterdam, ^d Dutch Cochrane Centre, Academic Medical Centre, University of Amsterdam

Correspondence to: Mr de Craen.

Abstract

Objectives: To assess whether adding codeine to paracetamol has an additive analgesic effect; to assess the safety of paracetamol-codeine combinations versus paracetamol alone.
Design: Systematic literature review with meta-analysis, methodological quality of published trials being scored by means of 13 predefined criteria.
Trials: 24 of 29 trials that met the inclusion criteria. Models studied in the trials were postsurgical pain (21), postpartum pain (one), osteoarthritic pain (one), and experimentally induced pain (one).
Interventions: Dosages ranged from 400 to 1000 mg paracetamol and 10 to 60 mg codeine.
Main outcome measures: The sum pain intensity difference (efficacy analysis) and the proportion of patients reporting a side effect (safety analysis).
Results: Most trials were considered of good to very good quality. Only the single dose studies could be combined for analysis of analgesic efficacy. Pooled efficacy results indicated that codeine added to paracetamol provided a 5% increase in analgesia on the sum pain intensity difference. This effect was comparable to the difference in analgesic effect between codeine and placebo. The cumulative incidence of side effects with each treatment was comparable in the single dose trials. In the multidose studies a significantly higher proportion of side effects occurred with paracetamol-codeine preparations.
Conclusion: The difference in analgesic effect between paracetamol-codeine combinations and paracetamol alone was small but statistically significant. In the multidose studies the proportion of patients reporting a side effect was significantly higher with paracetamol-codeine combinations. For occasional pain relief a paracetamol-codeine combination might be appropriate but repeated use increases the occurrence of side effects.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    StumbleUpon    Technorati    What's this?

Relevant Articles

Paracetamol-codeine combinations versus paracetamol alone

A Li Wan Po and W Y Zhang
BMJ 1996 313: 1209. [Extract] [Full Text]

Intention to treat approach is not popular

Lasse A Skoglund
BMJ 1996 313: 1209. [Extract] [Full Text]

Actual size of increase needs to be measured

Sally Collins, Andrew Moore, and Henry McQuay
BMJ 1996 313: 1209. [Extract] [Full Text]

This article has been cited by other articles:

• Ali, S., Klassen, T. P (2007). Ibuprofen was more effective than codeine or acetaminophen for musculoskeletal pain in children. Evid. Based Med. 12: 144-144 [Full text]  
• Zhang, W, Doherty, M, Arden, N, Bannwarth, B, Bijlsma, J, Gunther, K-P, Hauselmann, H J, Herrero-Beaumont, G, Jordan, K, Kaklamanis, P, Leeb, B, Lequesne, M, Lohmander, S, Mazieres, B, Martin-Mola, E, Pavelka, K, Pendleton, A, Punzi, L, Swoboda, B, Varatojo, R, Verbruggen, G, Zimmermann-Gorska, I, Dougados, M (2005). EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 64: 669-681 [Abstract] [Full text]  
• Stockler, M., Vardy, J., Pillai, A., Warr, D. (2004). Acetaminophen (Paracetamol) Improves Pain and Well-Being in People With Advanced Cancer Already Receiving a Strong Opioid Regimen: A Randomized, Double-Blind, Placebo-Controlled Cross-Over Trial. JCO 22: 3389-3394 [Abstract] [Full text]  
• Wang, C.-T., Lin, J., Chang, C.-J., Lin, Y.-T., Hou, S.-M. (2004). Therapeutic Effects of Hyaluronic Acid on Osteoarthritis of the Knee. A Meta-Analysis of Randomized Controlled Trials. JBJS 86: 538-545 [Abstract] [Full text]  
• Maurice, S C, O'Donnell, J J, Beattie, T F (2002). Emergency analgesia in the paediatric population. Part II Pharmacological methods of pain relief. Emerg. Med. J. 19: 101-105 [Abstract] [Full text]  
• Romsing, J., Moiniche, S., Dahl, J. B. (2002). Rectal and parenteral paracetamol, and paracetamol in combination with NSAIDs, for postoperative analgesia. Br J Anaesth 88: 215-226 [Abstract] [Full text]  
• Williams, D. G., Hatch, D. J., Howard, R. F. (2001). Codeine phosphate in paediatric medicine. Br J Anaesth 86: 413-421 [Abstract] [Full text]  
• T-L. Choi, P., Halpern, S. H., Malik, N., Jadad, A. R., Tramer, M. R., Walder, B. (2001). Examining the Evidence in Anesthesia Literature: A Critical Appraisal of Systematic Reviews. Anesth. Analg. 92: 700-709 [Abstract] [Full text]  
• Smith, B. H, Hopton, J. L, Chambers, W A. (1999). Chronic pain in primary care. Fam Pract 16: 475-482 [Abstract] [Full text]  
• Eccles, M., Freemantle, N., Mason, J. (1998). North of England evidence based guideline development project: summary guideline for non-steroidal anti-inflammatory drugs versus basic analgesia in treating the pain of degenerative arthritis. BMJ 317: 526-530 [Full text]  
• Po, A L. W., Zhang, W Y (1997). Systematic overview of co-proxamol to assess analgesic effects of addition of dextropropoxyphene to paracetamol. BMJ 315: 1565-1571 [Abstract] [Full text]  
• Davies, S. C, Oni, L. (1997). Fortnightly review: Management of patients with sickle cell disease. BMJ 315: 656-660 [Full text]  
• Po, A L. W., Zhang, W Y (1996). Paracetamol-codeine combinations versus paracetamol alone. BMJ 313: 1209-1209 [Full text]  
• Skoglund, L. A (1996). Intention to treat approach is not popular. BMJ 313: 1209a-1209 [Full text]  
• Collins, S., Moore, A., McQuay, H. (1996). Actual size of increase needs to be measured. BMJ 313: 1209b-1209 [Full text]