Twenty-two RCTs (670 opioid-treated patients) were included in the review. Of these, 14 were short-term crossover RCTs (n=267) and 8 were intermediate-terms RCTs (5 crossover and 3 parallel group; n=799).
The median Jadad score for all studies was 4 (range: 2 to 5).
Intermediate-term trials (8 RCTs).
Six studies scored 5 points on the Jadad score for validity.
A meta-analysis of 6 RCTs (n=521) found that the mean post-treatment VAS score for pain intensity after opioid use was 14 units lower on a 0- to 100-mm scale than after placebo (95% CI: -18, -10, P<0.001). No statistically significant heterogeneity was detected (P=0.27).
Short-term trials (14 RCTs).
The short-term individual trials had mixed results. Only 4 RCTs presented sufficient data for a meta-analysis. The meta-analysis showed that opioids reduced peripheral pain (WMD -15, 95% CI: -23, -7), based on 138 patients, and central pain (WMD -18, 95% CI: -30, -5), based on 42 patients. No statistically significant heterogeneity was detected (P=0.94 and P=0.78, respectively).
Adverse events.
The most common adverse event was nausea (NNH 3.6, 95% CI: 2.9, 4.8), followed by constipation (NNH 4.6, 95% CI: 3.4, 7.1), drowsiness (NNH 5.3, 95% CI: 3.7, 8.3), vomiting (NNH 6.2, 95% CI: 4.6, 11.1) and dizziness (NNH 6.7, 95% CI: 4.8, 10.0).
The funnel plot showed no evidence of publication bias among intermediate-term trials.