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Chou R, Deyo R, Devine B, et al. The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014 Sep. (Evidence Reports/Technology Assessments, No. 218.)
This publication is provided for historical reference only and the information may be out of date.
Table ASummary of evidence
| Key Question Outcome | Strength of Evidence Grade | Conclusion |
|---|---|---|
| 1. Effectiveness and comparative effectiveness | ||
| a. In patients with chronic pain, what is the effectiveness of long-term opioid therapy versus placebo or no opioid therapy for long-term (≥1 year) outcomes related to pain, function, and quality of life? | ||
| Pain, function, quality of life | Insufficient | No study of opioid therapy versus placebo or no opioid therapy evaluated long-term (≥1 year) outcomes related to pain, function, or quality of life |
| b. How does effectiveness vary depending on: 1) the specific type or cause of pain (e.g., neuropathic, musculoskeletal [including low back pain], fibromyalgia, sickle cell disease, inflammatory pain, and headache disorders); 2) patient demographics (e.g., age, race, ethnicity, gender); 3) patient comorbidities (including past or current alcohol or substance use disorders, mental health disorders, medical comorbidities and high risk for addiction)? | ||
| Pain, function, quality of life | Insufficient | No studies |
| c. In patients with chronic pain, what is the comparative effectiveness of opioids versus nonopioid therapies (pharmacological or nonpharmacological) on outcomes related to pain, function, and quality of life? | ||
| Pain, function, quality of life | Insufficient | No studies |
| d. In patients with chronic pain, what is the comparative effectiveness of opioids plus nonopioid interventions (pharmacological or nonpharmacological) versus opioids or nonopioid interventions alone on outcomes related to pain, function, quality of life, and doses of opioids used? | ||
| Pain, function, quality of life | Insufficient | No Studies |
| 2. Harms and adverse events | ||
| a. In patients with chronic pain, what are the risks of opioids versus placebo or no opioid on: 1) opioid abuse, addiction, and related outcomes; 2) overdose; and 3) other harms, including gastrointestinal-related harms, falls, fractures, motor vehicle accidents, endocrinological harms, infections, cardiovascular events, cognitive harms, and psychological harms (e.g., depression)? | ||
| Abuse, addiction | Low | No randomized trial evaluated risk of opioid abuse, addiction, and related outcomes in patients with chronic pain prescribed opioid therapy. One retrospective cohort study found prescribed long-term opioid use associated with significantly increased risk of abuse or dependence versus no opioid use. |
| Abuse, addiction | Insufficient | In 10 uncontrolled studies, estimates of opioid abuse, addiction, and related outcomes varied substantially even after stratification by clinic setting |
| Overdose | Low | Current opioid use was associated with increased risk of any overdose events (adjusted HR 5.2, 95% CI 2.1 to 12) and serious overdose events (adjusted HR 8.4, 95% CI 2.5 to 28) versus current nonuse |
| Fractures | Low | Opioid use associated with increased risk of fracture in 1 cohort study (adjusted HR 1.28, 95% CI 0.99 to 1.64) and 1 case-control study (adjusted OR 1.27, 95% CI 1.21 to 1.33) |
| Myocardial infarction | Low | Current opioid use associated with increased risk of myocardial infarction versus nonuse (adjusted OR 1.28, 95% CI 1.19 to 1.37 and incidence rate ratio 2.66, 95% CI 2.30 to 3.08) |
| Endocrine | Low | Long-term opioid use associated with increased risk of use of medications for erectile dysfunction or testosterone replacement versus nonuse (adjusted OR 1.5, 95% CI 1.1 to 1.9) |
| Gastrointestinal harms, motor vehicle accidents, infections, psychological harms, cognitive harms | Insufficient | No studies |
| b. How do harms vary depending on: 1) the specific type or cause of pain (e.g., neuropathic, musculoskeletal [including back pain], fibromyalgia, sickle cell disease, inflammatory pain, headache disorders); 2) patient demographics; 3) patient comorbidities (including past or current substance use disorder or at high risk for addiction)? | ||
| Various harms | Insufficient | No studies |
| b. How do harms vary depending on the dose of opioids used? | ||
| Abuse, addiction | Low | One retrospective cohort study found higher doses of long-term opioid therapy associated with increased risk of opioid abuse or dependence than lower doses. Compared to no opioid prescription, the adjusted odds ratios were 15 (95 percent CI 10 to 21) for 1-36 MED/day, 29 (95 percent CI 20 to 41) for 36-120 MED/day, and 122 (95 percent CI 73 to 205) for ≥120 MED/day. |
| Overdose | Low | Versus 1 to 19 mg MED/day, 1 cohort study found an adjusted HR for an overdose event of 1.44 (95% CI 0.57 to 3.62) for 20 to 49 mg MED/day that increased to 11.18 (95% CI 4.80 to 26.03) at >100 mg MED/day; 1 case-control study found an adjusted OR for an opioid-related death of 1.32 (95% CI 0.94 to 1.84) for 20 to 49 mg MED/day that increased to 2.88 (95% CI 1.79 to 4.63) at ≥200 mg MED/day |
| Fracture | Low | Risk of fracture increased from an adjusted HR of 1.20 (95% CI 0.92 to 1.56) at 1 to <20 mg MED/day to 2.00 (95% CI 1.24 to 3.24) at ≥50 mg MED/day; the trend was of borderline statistical significance |
| Myocardial infarction | Low | Relative to a cumulative dose of 0 to 1350 mg MED over 90 days, the incidence rate ratio for myocardial infarction for 1350 to <2700 mg was 1.21 (95% CI 1.02 to 1.45), for 2700 to <8100 mg was 1.42 (95% CI 1.21 to 1.67), for 8100 to <18,000 mg was 1.89 (95% CI 1.54 to 2.33), and for >18,000 mg was 1.73 (95% CI 1.32 to 2.26) |
| Motor vehicle accidents | Low | No association between opioid dose and risk of motor vehicle accidents. |
| Endocrine | Low | Relative to 0 to <20 mg MED/day, the adjusted OR for daily opioid dose of ≥120 mg MED/day for use of medications for erectile dysfunction or testosterone replacement was 1.6 (95% CI 1.0 to 2.4) |
| 3. Dosing strategies | ||
| a. In patients with chronic pain, what is the comparative effectiveness of different methods for initiating and titrating opioids for outcomes related to pain, function, and quality of life; risks of overdose, addiction, abuse, or misuse; and doses of opioids used? | ||
| Pain | Insufficient | Evidence from three trials on effects of titration with immediate-release versus sustained-release opioids reported inconsistent results on outcomes related to pain and are difficult to interpret due to additional differences between treatment arms in dosing protocols (titrated vs. fixed dosing) and doses of opioids used |
| Function, quality of life, outcomes related to abuse | Insufficient | No studies |
| b. In patients with chronic pain, what is the comparative effectiveness of short- versus long-acting opioids on outcomes related to pain, function, and quality of life; risk of overdose, addiction, abuse, or misuse; and doses of opioids used? | ||
| Pain, function, quality of life, outcomes related to abuse | Insufficient | No studies |
| c. In patients with chronic pain, what is the comparative effectiveness of different long- acting opioids on outcomes related to pain, function, and quality of life; and risk of overdose, addiction, abuse, or misuse? | ||
| Pain and function | Low | No difference between various long-acting opioids |
| Assessment of risk of overdose, addiction, abuse, or misuse | Insufficient | No studies were designed to assess risk of overdose, addiction, abuse, or misuse |
| Overdose (as indicated by all-cause mortality) | Low | One cohort study found methadone to be associated with lower all-cause mortality risk than sustained-release morphine in a propensity adjusted analysis |
| Abuse and related outcomes | Insufficient | Another cohort study found some differences between long-acting opioids in rates of adverse outcomes related to abuse, but outcomes were nonspecific for opioid-related adverse events, precluding reliable conclusions |
| d. In patients with chronic pain, what is the comparative effectiveness of short- plus long- acting opioids vs. long-acting opioids alone on outcomes related to pain, function, and quality of life; risk of overdose, addiction, abuse, or misuse; and doses of opioids used? | ||
| Pain, function, quality of life, outcomes related to abuse | Insufficient | No studies |
| e. In patients with chronic pain, what is the comparative effectiveness of scheduled, continuous versus as-needed dosing of opioids on outcomes related to pain, function, and quality of life; risk of overdose, addiction, abuse, or misuse; and doses of opioids used? | ||
| Pain, function, quality of life, outcomes related to abuse | Insufficient | No studies |
| f. In patients with chronic pain on long-term opioid therapy, what is the comparative effectiveness of dose escalation versus dose maintenance or use of dose thresholds on outcomes related to pain, function, and quality of life? | ||
| Pain, function, withdrawal due to opioid misuse | Low | No difference between more liberal dose escalation versus maintenance of current doses in pain, function, or risk of withdrawal due to opioid misuse, but there was limited separation in opioid doses between groups (52 vs. 40 mg MED/day at the end of the trial) |
| g. In patients on long-term opioid therapy, what is the comparative effectiveness of opioid rotation versus maintenance of current opioid therapy on outcomes related to pain, function, and quality of life; and doses of opioids used? | ||
| Pain, function, quality of life, outcomes related to abuse | Insufficient | No studies |
| h. In patients on long-term opioid therapy, what is the comparative effectiveness of different strategies for treating acute exacerbations of chronic pain on outcomes related to pain, function, and quality of life? | ||
| Pain | Moderate | Two randomized trials found buccal fentanyl more effective than placebo for treating acute exacerbations of pain and three randomized trials found buccal fentanyl or intranasal fentanyl more effective than oral opioids for treating acute exacerbations of pain in patients on long-term opioid therapy, based on outcomes measured up to 2 hours after dosing |
| Abuse and related outcomes | Insufficient | No studies |
| i. In patients on long-term opioid therapy, what are the effects of decreasing opioid doses or of tapering off opioids versus continuation of opioids on outcomes related to pain, function, quality of life, and withdrawal? | ||
| Pain, function | Insufficient | Abrupt cessation of morphine was associated with increased pain and decreased function compared to continuation of morphine |
| j. In patients on long-term opioid therapy, what is the comparative effectiveness of different tapering protocols and strategies on measures related to pain, function, quality of life, withdrawal symptoms, and likelihood of opioid cessation? | ||
| Opioid abstinence | Insufficient | No clear differences between different methods for opioid discontinuation or tapering in likelihood of opioid abstinence after 3 to 6 months |
| 4. Risk assessment and risk mitigation strategies | ||
| a. In patients with chronic pain being considered for long-term opioid therapy, what is the accuracy of instruments for predicting risk of opioid overdose, addiction, abuse, or misuse? | ||
| Diagnostic accuracy: Opioid Risk Tool | Insufficient | Based on a cutoff of >4, three studies (one poor- quality, two poor-quality) reported very inconsistent estimates of diagnostic accuracy, precluding reliable conclusions |
| Diagnostic accuracy: Screening and Opioid Assessment for Patients with Pain (SOAPP) version 1 | Low | Based on a cutoff score of ≥8, sensitivity was 0.68 and specificity of 0.38 in 1 study, for a PLR of 1.11 and NLR of 0.83. Based on a cutoff score of >6, sensitivity was 0.73 in 1 study |
| b. In patients with chronic pain, what is the effectiveness of use of risk prediction instruments on outcomes related to overdose, addiction, abuse, or misuse? | ||
| Outcomes related to abuse | Insufficient | No study evaluated the effectiveness of risk prediction instruments for reducing outcomes related to overdose, addiction, abuse, or misuse |
| c. In patients with chronic pain prescribed long- term opioid therapy, what is the effectiveness of risk mitigation strategies, including 1) opioid management plans, 2) patient education, 3) urine drug screening, 4) use of prescription drug monitoring program data, 5) use of monitoring instruments, 6) more frequent monitoring intervals, 7) pill counts, and 8) use of abuse-deterrent formulations on outcomes related to overdose, addiction, abuse, or misuse? | ||
| Outcomes related to abuse | Insufficient | No studies |
| d. What is the comparative effectiveness of treatment strategies for managing patients with addiction to prescription opioids on outcomes related to overdose, abuse, misuse, pain, function, and quality of life? | ||
| Outcomes related to abuse | Insufficient | No studies |
Abbreviations: CI=confidence interval, HR=hazard ratio, MED= morphine equivalent dose, mg=milligrams, NLR=negative likelihood ratio, OR=odds ratio, PLR=positive likelihood ratio, SOAPP= Screening and Opioid Assessment for Patients with Pain.
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