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Meta-Analysis
. 2010 Apr 14;2010(4):CD008099.
doi: 10.1002/14651858.CD008099.pub2.

Single dose oral codeine, as a single agent, for acute postoperative pain in adults

Sheena Derry  1 , R Andrew Moore, Henry J McQuay
Affiliations
Meta-Analysis

Single dose oral codeine, as a single agent, for acute postoperative pain in adults

Sheena Derry et al. Cochrane Database Syst Rev. .

Abstract

Background: Codeine is an opioid metabolised to active analgesic compounds, including morphine. It is widely available by prescription, and combination drugs including low doses of codeine are commonly available without prescription.

Objectives: To assess the efficacy, the time to onset of analgesia, the time to use of rescue medication and any associated adverse events of single dose oral codeine in acute postoperative pain.

Search strategy: We searched CENTRAL, MEDLINE, EMBASE and PubMed to November 2009.

Selection criteria: Single oral dose, randomised, double-blind, placebo-controlled trials of codeine for relief of established moderate to severe postoperative pain in adults.

Data collection and analysis: Studies were assessed for methodological quality and data independently extracted by two review authors. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours were used to calculate the number of participants achieving at least 50% pain relief, which were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Data on adverse events and withdrawals were collected.

Main results: Thirty-five studies were included (1223 participants received codeine 60 mg, 27 codeine 90 mg, and 1252 placebo). Combining all types of surgery (33 studies, 2411 participants), codeine 60 mg had an NNT of at least 50% pain relief over 4 to 6 hours of 12 (8.4 to 18) compared with placebo. At least 50% pain relief was achieved by 26% on codeine 60 mg and 17% on placebo.Following dental surgery the NNT was 21 (12 to 96) (15 studies, 1146 participants), and following other types of surgery the NNT was 6.8 (4.6 to 13) (18 studies, 1265 participants). The NNT to prevent use of rescue medication within 4 to 6 hours was 11 (6.3 to 50) (11 studies, 765 participants, mostly non-dental); the mean time to its use was 2.7 hours with codeine and 2.0 hours with placebo. More participants experienced adverse events with codeine 60 mg than placebo; the difference was not significant and none were serious. Two adverse event withdrawals occurred with placebo.

Authors' conclusions: Single dose codeine 60 mg provides good analgesia to few individuals, and does not compare favourably with commonly used alternatives such as paracetamol, NSAIDs and their combinations with codeine, especially after dental surgery; the large difference between dental and other surgery was unexpected. Higher doses were not evaluated.

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Conflict of interest statement

RAM and HJM have undertaken research/consultancy for various pharmaceutical companies. RAM and HJM have received lecture fees from pharmaceutical companies for presentations on analgesics research and other healthcare interventions. RAM, HJM, and SD have received research support from charities, government and industry sources at various times; no such support was received for the preparation of this systematic review.

Figures

1
1
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
2
2
L'Abbé plot showing heterogeneity between studies in dental pain (blue) and in other types of surgery (cream). Study size is proportional to size of circle (inset scale)
3
3
Forest plot of comparison: 1 Codeine 60 mg versus placebo, outcome: 1.1 Participants with ≥50% pain relief over 4 to 6 hours.
4
4
Forest plot of comparison: 1 Codeine 60 mg versus placebo, outcome: 1.2 Participants using rescue medication within 4 to 6 hours.
5
5
Forest plot of comparison: 1 Codeine 60 mg versus placebo, outcome: 1.3 Participants with ≥1 adverse event.
1.1
1.1. Analysis
Comparison 1 Codeine 60 mg versus placebo, Outcome 1 Participants with ≥50% pain relief over 4 to 6 hours.
1.2
1.2. Analysis
Comparison 1 Codeine 60 mg versus placebo, Outcome 2 Participants using rescue medication within 4 to 6 hours.
1.3
1.3. Analysis
Comparison 1 Codeine 60 mg versus placebo, Outcome 3 Participants with ≥1 adverse event.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD008099

References

References to studies included in this review

Baird 1980 {published data only}
    1. Baird WM, Turek D. Comparison of zomepirac, APC with codeine, codeine and placebo in the treatment of moderate and severe postoperative pain. Journal of Clinical Pharmacology 1980;20(4 Pt 2):243‐9. - PubMed
Bentley 1987 {published data only}
    1. Bentley KC, Head TW. The additive analgesic efficacy of acetaminophen, 1000 mg, and codeine, 60 mg, in dental pain. Clinical Pharmacology and Therapeutics 1987;42(6):634‐40. - PubMed
Bloomfield 1981 {published data only}
    1. Bloomfield SS, Barden TP, Mitchell J. Propiram and codeine in episiotomy pain. International Journal of Clinical Pharmacology, Therapy, and Toxicology 1981;19(4):152‐7. - PubMed
Cooper 1982 {published data only}
    1. Cooper SA, Engel J, Ladov M, Precheur H, Rosenheck A, Rauch D. Analgesic efficacy of an ibuprofen‐codeine combination. Pharmacotherapy 1982;2(3):162‐7. - PubMed
Defoort 1983 {published data only}
    1. Defoort P, Thiery M, Martens G, Maele G. A double‐blind trial of single‐dose ciramadol for the treatment of post‐episiotomy pain. Current Medical Research and Opinion 1983;8(7):481‐6. - PubMed
Desjardins 1984 {published data only}
    1. Desjardins PJ, Cooper SA, Gallegos TL, Allwein JB, Reynolds DC, Kruger GO. The relative analgesic efficacy of propiram fumarate, codeine, aspirin, and placebo in post‐impaction dental pain. The Journal of Clinical Pharmacology 1984;24(1):35‐42. - PubMed
Forbes 1986 {published data only}
    1. Forbes JA, Keller CK, Smith JW, Zeleznock JR, Sevelius H, Beaver WT. Analgesic effect of naproxen sodium, codeine, a naproxen‐codeine combination and aspirin on the postoperative pain of oral surgery. Pharmacotherapy 1986;6:211‐8. - PubMed
Giglio 1990 {published data only}
    1. Giglio JA, Laskin DM. Double‐blind comparison of meclofenamate sodium plus codeine, meclofenamate sodium, codeine, and placebo for relief of pain following surgical removal of third molars. Journal of Oral and Maxillofacial Surgery : official journal of the American Association of Oral and Maxillofacial Surgeons 1990;48(8):785‐90. - PubMed
Hebertson 1986 {published data only}
    1. Hebertson RM, Storey N, Turner JL. Analgesic efficacy of meclofenamate sodium in episiotomy pain. Pharmacotherapy 1986;6(5):205‐10. - PubMed
Hersh 1993 {published data only}
    1. Hersh EV, Ochs H, Quinn P, MacAfee K, Cooper SA. Narcotic receptor blockade and its effect on the analgesic response to placebo and ibuprofen after oral surgery. Oral Surgery, Oral Medicine, and Oral Pathology 1993;75(5):539‐46. - PubMed
Honig 1984 {published data only}
    1. Honig S, Murray KA. An appraisal of codeine as an analgesic: single‐dose analysis. Journal of Clinical Pharmacology 1984;24(2‐3):96‐102. - PubMed
Jain 1988 {published data only}
    1. Jain A, McMahon FG, Ryan JR, Smith G, Berman R. A double‐blind study of diflunisal and codeine compared with codeine or diflunisal alone in postoperative pain. Clinical Pharmacology and Therapeutics 1988;43(5):529‐35. - PubMed
Mehlisch 1984 {published data only}
    1. Mehlisch D, Frakes L, Cavaliere MB, Gelman M. Double‐blind parallel comparison of single oral doses of ketoprofen, codeine, and placebo in patients with moderate to severe dental pain. The Journal of Clinical Pharmacology 1984;24(11‐12):486‐92. - PubMed
Moore 1997 {published data only}
    1. Moore PA, Crout RJ, Jackson DL, Schneider LG, Graves RW, Bakos L. Tramadol hydrochloride: analgesic efficacy compared with codeine, aspirin with codeine, and placebo after dental extraction. Journal of Clinical Pharmacology 1998;38(6):554‐60. - PubMed
    1. Moore RA, McQuay HJ. Single‐patient data meta‐analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics. Pain 1997;69(3):(3):287‐94. [DOI: 10.1016/S0304-3959(96)03291-5] - DOI - PubMed
Sunshine 1983 {published data only}
    1. Sunshine A, Laska EM, Olson NZ, Colon A, Gonzalez L, Tirado S. Analgesic effects of oral propiram fumarate, codeine sulfate and placebo in postoperative pain. Pharmacotherapy 1983;3(5):299‐30. - PubMed
Sunshine 1987 {published data only}
    1. Sunshine A, Roure C, Olson N, Laska EM, Zorrilla C, Rivera J. Analgesic efficacy of two ibuprofen‐codeine combinations for the treatment of postepisiotomy and postoperative pain. Clinical Pharmacology and Therapeutics 1987;42(4):374‐80. - PubMed
Sunshine 1988 {published data only}
    1. Sunshine A, Roure C, Colon A, Olson NZ, Gonzalez L, Siegel C, et al. Analgesic efficacy of piroxicam in the treatment of postoperative pain. The American Journal of Medicine 1988;20(84(5A)):16‐22. - PubMed
van Steenberghe 1986 {published data only}
    1. Steenberghe D, Verbist D, Quirynen M, Thevissen E. Double‐blind comparison of the analgesic potency of ciramadol, codeine and placebo against postsurgical pain in ambulant patients. European Journal of Clinical Pharmacology 1986;31(3):355‐8. - PubMed
Yonkeura 1987 {published data only}
    1. Yonkeura ML, Petrone S, Turner JL, Zerega GS. Double‐blind comparison of meclofenamate sodium with codeine and placebo for the pain of episiotomy. Clinical Therapeutics 1987;9(6):578‐84. - PubMed

References to studies excluded from this review

Brunelle 1988 {published data only}
    1. Brunelle RL, George RE, Sunshine A, Hammonds WD. Analgesic effect of picenadol, codeine, and placebo in patients with postoperative pain. Clinical Pharmacology and Therapeutics 1988;43(6):663‐7. - PubMed
Coutinho 1976 {published data only}
    1. Coutinho A, Bonelli J, Carvalho PC. A double‐blind comparative study of the analgesic effects of fenbufen, codeine, aspirin, propoxyphene and placebo. Current Therapeutic Research, Clinical and Experimental 1976;19(1):58‐65. - PubMed
Gleason 1987 {published data only}
    1. Gleason JA, Winer W, Turner JL. Comparison of meclofenamate sodium with codeine and placebo for the treatment of episiotomy pain. Clinical Therapeutics 1987;9(6):585‐93. - PubMed
Offen 1985 {published data only}
    1. Offen WW, Gruber CM Jr. Dose response to fenoprofen calcium using placebo and codeine as controls. Journal of Medicine 1985;16(4):439‐52. - PubMed
Petersen 1978 {published data only}
    1. Petersen JK. The analgesic and anti‐inflammatory efficacy of diflunisal and codeine after removal of impacted third molars. Current Medical Research and Opinion 1978;5(7):525‐35. - PubMed

Additional references

Barden 2004
    1. Barden J, Edwards JE, McQuay HJ, Andrew Moore R. Pain and analgesic response after third molar extraction and other postsurgical pain. Pain 2004;107(1‐2):86‐90. [DOI: 10.1016/j.pain.2003.09.021] - DOI - PubMed
Bulley 2009
    1. Bulley S, Derry S, Moore RA, McQuay HJ. Single dose oral rofecoxib for acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD004604.pub3] - DOI - PMC - PubMed
Cascarbi 2003
    1. Cascarbi I. Pharmacogenetics of cytochrome P4502D6: genetic background and clinical implication. European Journal of Clinical Investigation 2003;33(Suppl 2):17‐22. - PubMed
Clarke 2009
    1. Clarke R, Derry S, Moore RA, McQuay HJ. Single dose oral etoricoxib for acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD004309.pub2] - DOI - PubMed
Collins 1997
    1. Collins SL, Moore RA, McQuay HJ. The visual analogue pain intensity scale: what is moderate pain in millimetres?. Pain 1997;72:95‐7. - PubMed
Collins 2001
    1. Collins SL, Edwards J, Moore RA, Smith LA, McQuay HJ. Seeking a simple measure of analgesia for mega‐trials: is a single global assessment good enough?. Pain 2001;91(1‐2):189‐94. - PubMed
Cook 1995
    1. Cook D, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. BMJ 1995;310:452‐4. - PMC - PubMed
Cooper 1991
    1. Cooper SA. Single‐dose analgesic studies: the upside and downside of assay sensitivity. In: Max MB, Portenoy RK, Laska EM editor(s). The design of analgesic clinical trials (Advances in Pain Research and Therapy). Vol. 18, New York: Raven Press, 1991:117‐24.
Derry 2008
    1. Derry S, Moore RA, McQuay HJ. Single dose oral celecoxib for acute postoperative pain. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD004233] - DOI - PubMed
Derry C 2009a
    1. Derry C, Derry S, Moore RA, McQuay HJ. Single dose oral naproxen and naproxen sodium for acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD004234.pub2] - DOI - PMC - PubMed
Derry C 2009b
    1. Derry C, Derry S, Moore RA, McQuay HJ. Single dose oral ibuprofen for acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 3. [DOI: 10.1002/14651858.CD001548] - DOI - PMC - PubMed
Derry P 2009
    1. Derry P, Derry S, Moore RA, McQuay HJ. Single dose oral diclofenac for acute postoperative pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD004768.pub2] - DOI - PMC - PubMed
Jadad 1996a
    1. Jadad A, Carroll D, Moore RA, McQuay HJ. Developing a database of published reports of randomised clinical trials in pain research. Pain 1997;66:239‐46. - PubMed
Jadad 1996b
    1. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Controlled Clinical Trials 1996;17:1‐12. - PubMed
L'Abbe 1987
    1. L'Abbé KA, Detsky AS, O'Rourke K. Meta‐analysis in clinical research. Annals of Internal Medicine 1987;107:224‐33. - PubMed
McQuay 1982
    1. McQuay HJ, Bullingham RE, Moore RA, Evans PJ, Lloyd JW. Some patients don't need analgesics after surgery. Journal of the Royal Society of Medicine 1982;75(9):705‐8. - PMC - PubMed
McQuay 2005
    1. McQuay HJ, Moore RA. Placebo. Postgraduate Medical Journal 2005;81:155‐60. [DOI: 10.1136/pgmj.2004.024737] - DOI - PMC - PubMed
Moher 1999
    1. Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of meta‐analyses of randomised controlled trials: the QUOROM statement. Lancet 1999;354:1896‐900. - PubMed
Moore 1996
    1. Moore A, McQuay H, Gavaghan D. Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics. Pain 1996;66(2‐3):229‐37. [DOI: 10.1016/0304-3959(96)03032-1] - DOI - PubMed
Moore 1997a
    1. Moore A, McQuay H, Gavaghan D. Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics: Verification from independent data. Pain 1997;69(1‐2):127‐30. [DOI: 10.1016/S0304-3959(96)03251-4] - DOI - PubMed
Moore 1997b
    1. Moore A, Moore O, McQuay H, Gavaghan D. Deriving dichotomous outcome measures from continuous data in randomised controlled trials of analgesics: Use of pain intensity and visual analogue scales. Pain 1997;69(3):311‐5. [DOI: 10.1016/S0304-3959(96)03306-4] - DOI - PubMed
Moore 1998
    1. Moore RA, Gavaghan D, Tramer MR, Collins SL, McQuay HJ. Size is everything‐large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects. Pain 1998;78(3):209‐16. [DOI: 10.1016/S0304-3959(98)00140-7] - DOI - PubMed
Moore 2003
    1. Moore RA, Edwards J, Barden J, McQuay HJ. Bandolier's Little Book of Pain. Oxford: Oxford University Press, 2003. [ISBN: 0‐19‐263247‐7]
Moore 2005
    1. Moore RA, Edwards JE, McQuay HJ. Acute pain: individual patient meta‐analysis shows the impact of different ways of analysing and presenting results. Pain 2005;116(3):322‐31. [DOI: 10.1016/j.pain.2005.05.001] - DOI - PubMed
Morris 1995
    1. Morris JA, Gardner MJ. Calculating confidence intervals for relative risk, odds ratio and standardised ratios and rates. In: Gardner M J, Altman DG editor(s). Statistics with confidence ‐ confidence intervals and statistical guidelines. London: British Medical Journal, 1995:50‐63. - PMC - PubMed
PCA 2008
    1. Anonymous. Prescription cost analysis, England 2008. NHS Information Centre, 2008. [ISBN: 978 ‐1‐84636‐292‐7]
Toms 2008
    1. Toms L, McQuay HJ, Derry S, Moore RA. Single dose oral paracetamol (acetaminophen) for postoperative pain in adults. Cochrane Database of Systematic Reviews 2008, Issue 4. [DOI: 10.1002/14651858.CD004602.pub2] - DOI - PMC - PubMed
Toms 2009
    1. Toms L, Derry S, Moore RA, McQuay HJ. Single dose oral paracetamol (acetaminophen) with codeine for postoperative pain in adults. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD001547.pub2] - DOI - PMC - PubMed
Tramer 1997
    1. Tramèr MR, Reynolds DJM, Moore RA, McQuay HJ. Impact of covert duplicate results on meta‐analysis: a case study. BMJ 1997;315:635‐9. - PMC - PubMed

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