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.
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.
We searched CENTRAL, MEDLINE, EMBASE and PubMed to November 2009.
Single oral dose, randomised, double‐blind, placebo‐controlled trials of codeine for relief of established moderate to severe postoperative pain in adults.
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.
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.
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.
Sheena Derry, R Andrew Moore, Henry J McQuay
Single dose oral codeine, as a single agent, for acute postoperative pain in adults
This review assessed evidence from 2411 adults with moderate to severe postoperative pain in studies comparing single doses of codeine 60 mg with placebo. The number of individuals achieving a clinically useful amount of pain relief (at least 50%) with codeine compared to placebo was low. In all types of surgery combined, 12 participants would need to be treated with codeine 60 mg for one to experience this amount of pain relief who would not have done so with placebo. The need for use of additional analgesia within 4 to 6 hours was 38% with codeine compared with 46% with placebo, and the mean time to the use of additional analgesia was only slightly longer with codeine (2.7 hours) than with placebo (2 hours). More individuals experienced adverse events with codeine than with placebo, but the difference was not significant and none were serious or led to withdrawal. Other commonly used analgesics, alone and in combination with codeine 60 mg, provide better pain relief. Higher doses of codeine were not investigated in these studies.
Sheena Derry, R Andrew Moore, Henry J McQuay
Implications for practice
Single doses of codeine 60 mg provide poor levels of analgesia in acute postoperative dental pain compared with other commonly used analgesics, such as ibuprofen, as measured by both numbers of participants achieving clinically useful levels of pain relief and duration of analgesia; better results are obtained for other types of postoperative pain, though these results are still relatively poor compared with other analgesics. In situations where an NSAID is contraindicated, paracetamol 1000 mg is likely to be a more effective option, and particularly the combination of paracetamol 1000 mg plus codeine 60 mg.
Implications for research
It seems unlikely that further studies will use codeine as a single agent in acute pain situations, given the availability of good alternatives in terms of NSAIDs and paracetamol/opioid or NSAID/opioid combinations. Higher doses may provide better pain relief but adverse events are likely to be unacceptable. More understanding of the efficacy of fixed combinations of paracetamol with codeine would be welcome, as would more understanding of potential differences in sensitivity of pain models to analgesic drugs with different mechanisms of action.Get full text at The Cochrane Library
Evidence Central is an integrated web and mobile solution that helps clinicians quickly answer etiology, diagnosis, treatment, and prognosis questions using the latest evidence-based research. Complete Product Information.