Opioids for chronic nonmalignant pain
Level of evidence: B
Opioids likely reduce chronic pain slightly.
A systematic review and meta-analysis «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA 2018;320(23):2448-2460 »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 effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann»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 Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA 2018;320(23):2448-2460 »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 Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA 2018;320(23):2448-2460 »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 | |||||
| «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA 2018;320(23):2448-2460 »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 | |||||
| «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA 2018;320(23):2448-2460 »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 Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA 2018;320(23):2448-2460 »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 | |||||
| «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA 2018;320(23):2448-2460 »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 | |||||
| «Busse JW, Wang L, Kamaleldin M, ym. Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA 2018;320(23):2448-2460 »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) |
References
- Busse JW, Wang L, Kamaleldin M, ym. Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis. JAMA 2018;320(23):2448-2460 «PMID: 30561481»PubMed
- Chou R, Turner JA, Devine EB, ym. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med 2015;162(4):276-86 «PMID: 25581257»PubMed