A systematic review and meta-analysis «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Ch...»1 measured the effectiveness of opioids compared to placebo in patients with chronic pain at 1-6 months follow up. Opioids decreased the pain by -0.79 points (95% CI -0.90 to -0.68, scale 0-10), which translates to about 16% decrease in pain. A subgroup analysis suggested a slightly smaller absolute effect in long term use (under 3 months vs 3 months or more).
In addition to pain relief, opioid use slightly improved physical functioning (2.0 points on a 100-point scale, 95% CI 1.41 to 2.68) and sleep quality (3.4 mm on a 100 mm scale, 95% CI 1.58 to 5.26) compared with placebo.
Compared with placebo, opioid use was associated with a higher incidence of vomiting (risk difference [RD] 7.1%, 95% CI 5.4%-9.3%).
Except for headache, opioid use was associated with a higher incidence of all other reported adverse effects: nausea (RD 18 %), constipation (RD 11 %), dizziness (RD 10 %), drowsiness (RD 11%), pruritus (RD 6 %) and dry mouth (RD 3 %).
Addiction rates were not reported. However, another systematic review «Chou R, Turner JA, Devine EB, ym. The effectivenes...»2 estimated addiction and opioid abuse rates in chronic pain using data from observational studies. The rates for dependence ranged between 2 % and 26 %. The risk of dependency is likely affected by drug dose and length of treatment.
The quality of evidence was downgraded due to moderate risk of bias.
| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Ch...»1 | SR and MA | Adults with any type of chronic nonmalignant pain | Oral or transdermal opioid vs nonopioid control for at least 4 weeks | Pain relief, physical functioning, vomiting | Moderate |
| Reference | Comments |
|---|---|
| «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Ch...»1 | Average pain score (0 – 10) at randomization 4.28 (23 enrichment trials) and 6.54
(51 nonenrichment trials). Median follow-up time 60 days. Median opioid dose in morphine equivalents/day 45 mg (range, 7 – 243 mg). Risk of bias: 51 (53%) adequately generated their randomization sequence, 48 (50%) adequately concealed allocation, 84 (88%) blinded patients, 84 (88%) blinded caregivers, 83 (87%) blinded data collectors, 82 (85%) blinded outcome assessors, and 6(6%) included a blinded data analyst. 76 % of trials had frequent (≥20%) missing data. |
Results
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Mean (sd) I | Mean (sd) C | Weighed mean difference (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to moderate risk of bias (large dropout rates). Furthermore, about 1/3 of the trials were enrichment trials (randomizing to placebo vs opioids after opioid treatment), raising some concerns of indirectness. *calculated by using estimated control mean at follow up I= intervention; C=comparison; CI=confidence interval |
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| «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Ch...»1 | 80 studies |
1-6 months | NA | 5.09 | -0.79 (-0.90 to -0.68), relative decrease -15.5 % (-17.6 % to -13.4 %)* |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of patients (%) I | Absolute number of patients (%) C | Risk difference (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to moderate risk of bias (large dropout rates). Furthermore, about 1/3 of the trials were enrichment trials (randomizing to placebo vs opioids after opioid treatment), raising some concerns of indirectness. I= intervention; C=comparison; CI=confidence interval; MID=minimally important difference |
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| «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Ch...»1 | All 96 studies 26169 |
1-6 months | NA | NA | 13.6 (11.8 to 15.4) |
| «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Ch...»1 | 42 studies with longer follow-up 16617 (9980/6637) |
3-6 months | 6048 (61%) | 3232 (49%) | 11.9 (9.7 to 14.1) |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of patients (%) I |
Absolute number of patients (%) C |
Risk difference (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: moderate The quality of evidence is downgraded due to moderate risk of bias (large dropout rates). Furthermore, about 1/3 of the trials were enrichment trials (randomizing to placebo vs opioids after opioid treatment), raising some concerns of indirectness. I= intervention; C=comparison; CI=confidence interval |
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| «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Ch...»1 | 51 studies 15754 (9263/6489) | 1-6 months | 5058 (55%) | 2992 (46%) | 8.5% (5.9% to 11.2%) |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative risk (95% CI) |
|---|---|---|---|---|---|
| Level of evidence: high The quality of evidence is downgraded due to moderate risk of bias (large dropout rates). I= intervention; C=comparison; CI=confidence interval |
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| «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Ch...»1 | 18 enrichment RCTs 5961 33 nonenrichment RCTs 11268 |
1-4 months 1-6 months |
179 (5.0) 667 (9.4) |
68 (2.3) 96 (2.3) |
2.50 (1.89 to 3.30) 4.02 (3.34 to 5.07) |