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Chou R, Hartung D, Turner J, et al. Opioid Treatments for Chronic Pain [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2020 Apr. (Comparative Effectiveness Review, No. 229.)
Table 26Pooled analyses of risk of nausea, vomiting, and constipation for opioids versus placebo
| Analysis | Nausea (95% CI) | I2 | # of Trials (N) | p* | Vomiting (95% CI) | I2 | # of Trials (N) | p* | Constipation (95% CI) | I2 | # of Trials (N) | p* |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| All trials | 2.46 (2.17 to 2.80) | 50% | 60 (19,718) | -- | 3.57 (2.98 to 4.34) | 15 | 49 (17,388) | -- | 3.38 (2.96 to 3.92) | 21% | 58 (19,351) | -- |
| Opioid type: Opioid agonist | 2.29 (1.90 to 2.74) | 46% | 32 (8581) | 0.06 | 3.17 (2.36 to 4.31) | 30 | 26 (7701) | 0.32 | 3.21 (2.74 to 3.87) | 7.4% | 31 (8478) | 0.10 |
| • Partial agonist | 1.99 (1.29 to 3.19) | 66% | 7 (2303) | -- | 3.65 (2.34 to 5.86) | 0 | 7 (2303) | -- | 2.53 (1.56 to 4.55) | 32% | 7 (2303) | -- |
| • Mixed mechanism | 2.97 (2.50 to 3.54) | 25% | 21 (8834) | -- | 4.19 (3.22 to 5.68) | 0 | 16 (7384) | -- | 3.82 (3.20 to 4.89) | 0.8% | 20 (8570) | -- |
| Pain type: Musculoskeletal | 2.43 (2.10 to 2.81) | 55% | 46 (17,508) | 0.64 | 3.57 (2.91 to 4.43) | 21 | 40 (15,601) | 0.89 | 3.34 (2.93 to 3.88) | 13% | 44 (17,141) | 0.93 |
| • Neuropathic | 2.51 (1.97 to 3.58) | 0% | 14 (2210) | -- | 3.90 (2.50 to 6.10) | 0 | 9 (1787) | -- | 3.78 (2.50 to 6.44) | 47% | 14 (2210) | -- |
| • Fibromyalgia | No studies | -- | -- | -- | No studies | -- | -- | -- | No studies | -- | -- | -- |
| Trial quality: Good | 2.14 (1.32 to 3.27) | 0% | 3 (1351) | 0.79 | 1.78 (0.71 to 4.10) | 0 | 2 (705) | 0.06 | 3.68 (2.40 to 5.58) | 0% | 3 (1351) | 0.96 |
| • Fair | 2.48 (2.15 to 2.86) | 52% | 48 (16,114) | -- | 3.58 (2.94 to 4.41) | 14 | 40 (14,813) | -- | 3.36 (2.90 to 3.98) | 21% | 47 (16,001) | -- |
| • Poor | 2.62 (1.68 to 4.28) | 34% | 9 (2253) | -- | 5.60 (3.18 to 10.36) | 0 | 7 (1870) | -- | 3.64 (1.97 to 9.28) | 48% | 8 (1999) | -- |
| Opioid dose (mg MED/day): <50 | 2.19 (1.63 to 3.08) | 39% | 13 (3936) | 0.68 | 3.61 (2.42 to 5.87) | 0 | 11 (3746) | 0.97 | 3.43 (2.23 to 5.50) | 50% | 12 (3823) | 0.97 |
| • 50–90 | 2.57 (2.13 to 3.08) | 19% | 19 (5920) | -- | 3.30 (2.40 to 5.10) | 0 | 13 (4414) | -- | 3.35 (2.79 to 4.27) | 5.7% | 18 (5666) | -- |
| • >90 | 2.51 (2.05 to 3.08) | 60% | 28 (9862) | -- | 3.61 (2.75 to 4.75) | 28 | 21 (9228) | -- | 3.36 (2.80 to 4.13) | 13% | 28 (9862) | -- |
| EERW design | 1.64 (1.40 to 1.94) | 5.8% | 22 (7872) | <0.005 | 2.46 (1.88 to 3.25) | 0 | 18 (6197) | 0.003 | 2.58 (2.03 to 3.38) | 1.0% | 21 (7618) | 0.03 |
| • Non-EERW design | 3.06 (2.70 to 3.48) | 24% | 38 (11,846) | -- | 4.33 (3.50 to 5.54) | 7.3 | 31 (11,191) | -- | 3.69 (3.17 to 4.47) | 24% | 37 (11,733) | -- |
| EERW design, 2007 or after | 1.62 (1.38 to 1.91) | 5.2% | 21 (7618) | <0.005 | 2.46 (1.88 to 3.25) | 0 | 18 (6197) | 0.009 | 2.58 (2.03 to 3.38) | 1.0% | 21 (7618) | 0.06 |
| • Non-EERW design | 2.91 (2.44 to 3.45) | 32% | 23 (8032) | -- | 4.10 (3.24 to 5.18) | 0 | 20 (7848) | -- | 3.70 (2.97 to 4.80) | 35% | 23 (8022) | -- |
| Crossover design | 2.45 (1.78 to 3.65) | 27% | 11 (1293) | 0.93 | 3.65 (2.04 to 6.81) | 0 | 7 (905) | 0.93 | 3.85 (2.47 to 6.66) | 43% | 11 (1293) | 0.95 |
| • Parallel group | 2.46 (2.14 to 2.83) | 52% | 49 (18,425) | -- | 3.57 (2.94 to 4.40) | 18 | 42 (16,483) | -- | 3.35 (2.96 to 3.83) | 6.2% | 47 (18,058) | -- |
| Opioids status: Naïve | 1.72 (1.30 to 2.51) | 26% | 11 (2566) | 0.007 | 3.60 (2.29 to 6.13) | 0 | 11 (2566) | 0.94 | 3.06 (2.03 to 4.84) | 27% | 11 (2566) | 0.35 |
| • Opioid experienced | 1.72 (1.10 to 2.57) | 48% | 7 (2242) | -- | 3.03 (1.34 to 6.48) | 53 | 7 (2242) | -- | 2.90 (1.86 to 5.32) | 0% | 7 (2242) | -- |
| • Mixed | 2.83 (2.44 to 3.28) | 40% | 33 (13,228) | -- | 3.62 (2.94 to 4.53) | 5.0 | 26 (11,409) | -- | 3.51 (3.12 to 4.07) | 0.4% | 32 (13,125) | -- |
| • Not reported | 2.74 (2.05 to 3.67) | 0% | 9 (1682) | -- | 3.50 (1.78 to 9.12) | 0 | 5 (1171) | -- | 3.19 (1.57 to 7.76) | 61% | 8 (1418) | -- |
| Publication: Prior to 2007 | 3.28 (2.72 to 4.18) | 14% | 16 (4068) | 0.003 | 5.65 (3.33 to 10.66) | 37 | 11 (3343) | 0.07 | 3.61 (2.86 to 5.04) | 12% | 14 (3711) | 0.29 |
| • In or after 2007 | 2.20 (1.90 to 2.56) | 51% | 44 (15,650) | -- | 3.30 (2.72 to 3.97) | 3.2 | 38 (14,045) | -- | 3.24 (2.73 to 3.90) | 30% | 44 (15,640) | -- |
| Region: USA or Canada | 2.41 (2.10 to 2.77) | 43% | 45 (14,654) | 0.25 | 3.27 (2.68 to 4.10) | 6.6 | 36 (13,005) | 0.52 | 3.54 (3.04 to 4.26) | 19% | 43 (14,287) | 0.24 |
| • Europe or Australia | 2.80 (1.84 to 4.33) | 63% | 9 (2900) | -- | 4.66 (2.68 to 8.63) | 36 | 8 (2865) | -- | 2.93 (2.18 to 4.21) | 0% | 9 (2900) | -- |
| • Asia | 1.50 (0.86 to 3.24) | 0% | 4 (495) | -- | 4.90 (1.73 to 13.89) | 0 | 4 (495) | -- | 1.75 (0.96 to 6.36) | 0% | 4 (495) | -- |
| • Multiple† | 3.68 (2.04 to 5.88) | 0% | 2 (1669) | -- | 3.53 (1.90 to 6.54) | -- | 1 (1023) | -- | 3.99 (2.45 to 6.08) | 0% | 2 (1669) | -- |
| Industry funding: Yes | 2.43 (2.13 to 2.78) | 51% | 54 (18,988) | 0.73 | 3.64 (3.01 to 4.44) | 16 | 48 (17,081) | -- | 3.43 (3.00 to 3.99) | 15% | 52 (18,621) | 0.64 |
| • No industry funding | 3.16 (1.26 to 7.37) | 15% | 5 (423) | -- | No studies | -- | -- | -- | 3.80 (1.64 to 10.30) | 54% | 5 (423) | -- |
Note: Statistically significant p values are bolded
Abbreviations: EERW=enriched enrollment randomized withdrawal; CI=confidence interval; MED=morphine equivalent dose; N= total sample size.
- *
p for interaction
- †
USA/Canada and Europe/Australia
- Table 26, Pooled analyses of risk of nausea, vomiting, and constipation for opio...Table 26, Pooled analyses of risk of nausea, vomiting, and constipation for opioids versus placebo - Opioid Treatments for Chronic Pain
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