Abdel Shaheed C, Maher CG, McLachlan AJ Efficacy and Safety of Low-dose Codeine-containing Combination Analgesics for Pain: Systematic Review and Meta-Analysis. Clin J Pain. 2019 Oct;35(10):836-843. doi: 10.1097/AJP.0000000000000746. (Systematic review)

OBJECTIVE: To investigate the efficacy and safety of combination analgesic products containing low-dose codeine (up to 30 mg/dose) for pain.

METHODS: Electronic databases were used to identify eligible placebo-controlled, randomized controlled trials (RCTs). Two authors extracted data and assessed the risk of bias. Data were pooled using a random-effects model with the strength of evidence assessed using Grading of Recommendations Assessment, Development and Evaluation. The primary outcome was immediate pain relief (3 hours post administration) on a 0 to 100 pain scale.

RESULTS: Ten RCTs were eligible. There is low-quality evidence (4 RCTs, n=211 participants) that a single dose of a combination analgesic product (with an nonsteroidal anti-inflammatory) containing low-dose codeine (15 to 30 mg) provides small pain relief for acute dental pain (mean difference [MD], -12.7; 95% confidence interval [CI], -18.5 to -6.9) and moderate-quality evidence (1 RCT, n=93) of small pain relief for post-episiotomy pain and orthopedic surgery pain (MD,, -10.0; 95% CI, -19.0 to -1.0 and MD, -11.0; 95% CI, -20.7 to -1.3), respectively. There is low-quality evidence (1 RCT, n=80) that a multiple-dose regimen provides small pain relief for acute pain following photorefractive keratectomy (MD, -16.0; 95% CI, -24.5 to -7.5) and moderate-quality evidence of moderate pain relief for certain chronic pain conditions: for hip osteoarthritis (MD, -19.0; 95% CI, -31.2 to -6.8) and for temporomandibular joint pain (MD, -26.0; 95% CI, -44.5 to -7.5). Two studies reported a higher incidence of drowsiness in the treatment group compared with the placebo group (relative risk, 8.50; 95% CI, 1.96, 36.8 and 19.3; 95% CI, 1.2-306.5, respectively).

DISCUSSION: There is low to moderate level evidence that combination analgesic products containing low-dose codeine provide small to moderate pain relief for acute and chronic pain conditions in the immediate short term with limited trial data on use beyond 24 hours. Further research examining regular use of these medicines is needed with more emphasis on measuring potential harmful effects.

Discipline Area Score
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Comments from MORE raters

Physician rater

Nothing new here but may be useful as a concise reference.

Physician rater

This systematic review looked at the efficacy and safety of analgesic combinations containing low dose codeine in a variety of pain related conditions. They found a total of 10 RCTs that met the inclusion criteria of the review and found low to moderate quality evidence to support efficacy of such codeine containing analgesic combinations with some evidence of toxicity. It is already recognised that such analgesic combinations have limited efficacy and a questionable benefit versus side effect profile and are of questionable value in anything other than acute short duration pain conditions. The usefulness in the management of any chronic pain condition is in considerable doubt.
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