Opioid Treatments for Chronic Pain

Project Summary Title and Description

Title
Opioid Treatments for Chronic Pain
Description
To assess the effectiveness and harms of opioid therapy for chronic noncancer pain; alternative opioid dosing strategies; and risk mitigation strategies
Attribution
N/A
Authors of Report
N/A
Methodology description
Predefined criteria were used to select studies of patients with chronic pain prescribed opioids that addressed effectiveness or harms versus placebo, no opioid use, or nonopioid pharmacological therapies; different opioid dosing methods; or risk mitigation strategies. Effects were analyzed at short term (1 to <6 months), intermediate term (≥6 to <12 months), and long term (≥12 months) followup. Studies on the accuracy of risk prediction instruments for predicting opioid use disorder or misuse were also included. Random effects meta-analysis was conducted on short-term trials of opioids versus placebo, opioids versus nonopioids, and opioids plus nonopioids versus an opioid or nonopioid alone. Magnitude of effects was classified as small, moderate, or large using predefined criteria and strength of evidence was assessed.
PROSPERO
CRD42019127423
DOI
N/A
Notes
https://effectivehealthcare.ahrq.gov/products/opioids-chronic-pain/protocol Data was entered retrospectively by importing data from Microsoft Excel. Table G-1. Quality Assessments of Randomized Controlled Trials Table G-2. Quality Assessments of Cohort Studies Table G-3. Quality Assessments of Case-control Studies Table G-4. Quality Assessments of Cross-sectional Studies Table G-5. Quality Assessments of Diagnostic Accuracy Studies Table H-1. Key Question 1: Long-Term Cohort Study of Opioids Versus Placebo For Chronic Pain – Study Characteristics Table H-2. Key Question 1: Long-Term Cohort Study of Opioids Versus Placebo For Chronic Pain – Study Results Table H-3. Key Question 1: Studies of Cannabis Use in Patients Prescribed Opioids For Chronic Pain – Study Characteristics Table H-4. Key Question 1: Studies of Cannabis Use in Patients Prescribed Opioids For Chronic Pain – Study Results Table H-5. Key Question 2a: Studies of Long-term Opioid Use and Abuse, Misuse, and Related Outcomes – Study Characteristics and Results Table H-6. Key Question 2a: Studies of Long-Term Opioid Use and Overdose – Study Characteristics Table H-7. Key Question 2a: Studies of Long-Term Opioid Use and Overdose – Study Results Table H-8. Key Question 2a: Studies of Long-Term Opioid Use and Fractures – Study Characteristics Table H-9. Key Question 2a: Studies of Long-Term Opioid Use and Fractures – Study Results Table H-10. Key Question 2a: Studies of Long-Term Opioid Use and Cardiovascular Outcomes – Study Characteristics Table H-11. Key Question 2a: Studies of Long-Term Opioid Use and Cardiovascular Outcomes – Study Results Table H-12: Key Question 2a: Study of Long-Term Opioid Use and Endocrine Outcomes – Study Characteristics Table H-13: Key Question 2a: Study of Long-Term Opioid Use and Endocrine Outcomes – Study Results Table H-14. Key Question 2a: Study of Long-Term Opioid Use and Motor Vehicle Accidents – Study Characteristics Table H-15. Key Question 2a: Study of Long-Term Opioid Use and Motor Vehicle Accidents – Study Results Table H-16. Key Question 2a: Studies of Long-Term Opioid Use and Risk of Depression – Study Characteristics Table H-17. Key Question 2a: Studies of Long-Term Opioid Use and Risk of Depression – Study Results Table H-18. Key Question 2: Studies of Co-Prescribing Benzodiazepines and Long-Term Opioids and Overdose – Study Characteristics Table H-19. Key Question 2: Studies of Co-Prescribing Benzodiazepines and Long-Term Opioids and Overdose – Study Results Table H-20 Key Question 2: Studies of Exposure to Gabapentin or Pregabalin in Long-Term Prescription Opioid Users with Chronic Pain – Study Characteristics Table H-21. Key Question 2: Studies of Exposure to Gabapentin or Pregabalin in Long-Term Prescription Opioid Users with Chronic Pain – Study Results Table H-22. Key Question 3a: Trials of Different Methods for Initiating and Titrating Opioids – Study Characteristics and Results Table H-23. Key Question 3b: Head-to-head Trials of Short-Acting Versus Long-Acting Opioids For Chronic Pain – Study characteristics Table H-24. Key Question 3b: Head-to-head Trials of Short-Acting Versus Long-Acting Opioids For Chronic Pain – Study Results Table H-25. Key Question 3b: Observational Studies of Short-Acting Versus Long-Acting Opioids For Chronic Pain – Study Characteristics Table H-26. Key Question 3b: Observational Studies of Short-Acting Versus Long-Acting Opioids For Chronic Pain – Study Results Table H-27. Key Question 3c: Head-to-Head Trials of Different Long-Acting Opioids – Study Characteristics Table H-28. Key Question 3c: Head-to-Head Trials of Different Long-Acting Opioids – Study Results Table H-29. Key Question 3c: Observational Studies of Different Long-Acting Opioids – Study Characteristics Table H-30. Key Question 3c: Observational Studies of Different Long-Acting Opioids – Study Results Table H-31. Key Question 3f: Trial of Opioid Dose Escalation Versus Dose Maintenance or Use of Maximum Dose Ceilings – Study Characteristics Table H-32. Key Question 3f: Trial of Opioid Dose Escalation Versus Dose Maintenance or Use of Maximum Dose Ceilings – Study Results Table H-33. Key Question 3h: Trials of Different Strategies for Treating Acute Exacerbations of Chronic Pain in Patients on Long-Term Opioid Therapy – Study Characteristics Table H-34. Key Question 3h: Trials of Different Strategies for Treating Acute Exacerbations of Chronic Pain in Patients on Long-Term Opioid Therapy – Study Results Table H-35. Key Question 3i: Trials of Decreasing Opioid Doses or of Tapering Off Opioids Versus Continuation of Opioids – Study Characteristics Table H-36. Key Question 3i: Trials of Decreasing Opioid Doses or of Tapering Off Opioids Versus Continuation of Opioids- Study Results Table H-37. Key Question 3i: Cohort Study of Decreasing Opioid Doses or of Tapering Off Opioids Versus Continuation of Opioids – Study Characteristics Table H-38. Key Question 3i: Cohort Study of Decreasing Opioid Doses or of Tapering Off Opioids Versus Continuation of Opioids – Study Results Table H-39. Key Question 3j. Trials of Different Opioid Tapering Protocols and Strategies – Study Characteristics Table H-40. Key Question 3j: Trials of Different Opioid Tapering Protocols and Strategies – Study Results Table H-41 Key Question 4a: Prospective Studies on Use of Screening Instruments to Predict the Risk of Aberrant Drug-Related Behaviors - Study Characteristics Table H-42 Key Question 4a: Prospective Studies on Use of Screening Instruments to Predict the Risk of Aberrant Drug-Related Behaviors - Study Results Table H-43. Key Question 4c: Study of Co-Prescription of Naloxone in Persons Prescribed Opioids For Chronic Pain – Study Characteristics and Results Table H-44. Key Question 4d: Studies of Treatment Strategies for Managing Patients with Opioid Use Disorder Related to Prescription Opioids -Study Characteristics Table H-45. Key Question 4d: Studies of Treatment Strategies for Managing Patients with Opioid Use Disorder Related to Prescription Opioids – Study Results Table I-1. Strength of Evidence and Key Findings
Funding Source
AHRQ Contract No. HHSA-290201500009I

Key Questions

1. Effectiveness and Comparative Effectiveness a. In patients with chronic pain, what is the effectiveness of opioids versus placebo or no opioid for outcomes related to pain, function, and quality of life, after short-term followup (1 to <6 months), intermediate-term followup (6 to <12 months), and long-term followup (≥12 months)? b. How does effectiveness vary depending on: (1) the specific type or cause of pain (e.g., neuropathic, musculoskeletal [including low back pain], visceral pain, fibromyalgia, sickle cell disease, inflammatory pain, headache disorders, and degree of nociplasticity); (2) patient demographics (e.g., age, race, ethnicity, gender, socioeconomic status); (3) patient comorbidities (including past or current alcohol or substance use disorders, mental health disorders, medical comorbidities and high risk for opioid use disorder); (4) the mechanism of action of opioids used (e.g., pure opioid agonists, partial opioid agonists such as buprenorphine, or drugs with mixed opioid and nonopioid mechanisms of action such as tramadol or tapentadol)? c. In patients with chronic pain, what is the comparative effectiveness of opioids versus nonopioid therapies (pharmacologic or nonpharmacologic, including cannabis) on outcomes related to pain, function, and quality of life, after short-term followup (1 to <6 months), intermediate-term followup (6 to <12 months), and long-term followup (≥12 months)? d. In patients with chronic pain, what is the comparative effectiveness of opioids plus nonopioid interventions (pharmacologic or nonpharmacologic, including cannabis) versus opioids or nonopioid interventions alone on outcomes related to pain, function, quality of life, and doses of opioids used, after short-term followup (1 to <6 months), intermediate-term followup (6 to <12 months), and long-term followup (≥12 months)?
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 use disorder, abuse, or misuse; (2) overdose (intentional and unintentional); 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)? b. How do harms vary depending on: (1) the specific type or cause of pain (e.g., neuropathic, musculoskeletal [including low back pain], visceral pain, fibromyalgia, sickle cell disease, inflammatory pain, headache disorders, and degree of nociplasticity); (2) patient demographics; (3) patient comorbidities (including past or current opioid use disorder or at high risk for opioid use disorder); (4) the dose of opioids used and duration of therapy; (5) the mechanism of action of opioids used (e.g., pure opioid agonists, partial opioid agonists such as buprenorphine, or drugs with opioid and nonopioid mechanisms of action such as tramadol and tapentadol); (6) use of sedative hypnotics; (7) use of gabapentinoids; (8) use of cannabis? c. In patients with chronic pain, what are the comparative risks of opioids versus nonopioid therapies on: (1) opioid use disorder, abuse, or misuse; (2) overdose (intentional and unintentional); and (3) other harms, including gastrointestinal-related harms, falls, fractures, motor vehicle accidents, endocrinological harms, infections, cardiovascular events, cognitive harms, and mental health harms (e.g., depression)? d. In patients with chronic pain, what are the comparative risks of opioids plus nonopioid interventions (pharmacologic or nonpharmacologic, including cannabis) versus opioids or nonopioid interventions alone on: (1) opioid use disorder, abuse, or misuse; (2) overdose (intentional and unintentional); and (3) other harms, including gastrointestinal-related harms, falls, fractures, motor vehicle accidents, endocrinological harms, infections, cardiovascular events, cognitive harms, and mental health harms (e.g., depression)?
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; risk of opioid use disorder, abuse, or misuse; overdose; and doses of opioids used? b. In patients with chronic pain, what is the comparative effectiveness of short-acting versus long-acting opioids on outcomes related to pain, function, and quality of life; risk of opioid use disorder, abuse, or misuse; overdose; and doses of opioids used? 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; risk of opioid use disorder, abuse, or misuse; and overdose? d. In patients with chronic pain, what is the comparative effectiveness of short- plus long-acting opioids versus long-acting opioids alone on outcomes related to pain, function, and quality of life; risk of opioid use disorder, abuse, or misuse; overdose; and doses of opioids used? 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 opioid use disorder, abuse, or misuse; overdose; and doses of opioids used? f. In patients with chronic pain, what is the comparative effectiveness of opioid dose escalation versus dose maintenance or use of dose thresholds on outcomes related to pain, function, and quality of life? g. In patients with chronic pain, 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? h. In patients with chronic pain, 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? i. In patients with chronic pain, 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 opiate withdrawal symptoms? j. In patients with chronic pain, what is the comparative effectiveness of different tapering protocols and strategies on measures related to pain, function, quality of life, opiate withdrawal symptoms, and likelihood of opioid cessation? k. In patients with chronic pain, what is the comparative effectiveness of different opioid dosages and durations of therapy for outcomes related to pain, function, and quality of life?
4. Risk Assessment and Risk Mitigation Strategies a. In patients with chronic pain being considered for opioid therapy, what is the accuracy of instruments and tests (including metabolic and/or genetic testing) for predicting risk of opioid use disorder, abuse, or misuse; and overdose? b. In patients with chronic pain, what is the effectiveness of use of risk prediction instruments and tests (including metabolic and/or genetic testing) on outcomes related to opioid use disorder, abuse, or misuse; and overdose? c. In patients with chronic pain who are prescribed 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, (8) use of abuse-deterrent formulations, (9) consultation with mental health providers when mental health conditions are present, (10) avoidance of co-prescribing of sedative hypnotics, and (11) co-prescribing of naloxone on outcomes related to opioid use disorder, abuse, or misuse; and overdose? d. In patients with chronic pain, what is the comparative effectiveness of treatment strategies for managing patients with opioid use disorder related to prescription opioids on outcomes related to pain, function, quality of life, opioid use disorder, abuse, misuse, and overdose?

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
A comparison of the abuse liability of tramadol, NSAIDs, and hydrocodone in patients with chronic pain.2006
A comparison of once-daily tramadol with normal release tramadol in the treatment of pain in osteoarthritis.2002
Efficacy and safety of Tapentadol extended release compared with oxycodone controlled release for the management of moderate to severe chronic pain related to osteoarthritis of the knee: a randomized, double-blind, placebo- and active-controlled phase III study.2010
Validation and clinical application of the Screener and Opioid Assessment for Patients with Pain (SOAPP).2006
Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain.2001
Transdermal fentanyl versus sustained release oral morphine in strong-opioid naïve patients with chronic low back pain.2005
Two placebo-controlled, randomized withdrawal studies to evaluate the fentanyl 1 day patch in opioid-naïve patients with chronic pain.
The efficacy and safety of fentanyl buccal tablet compared with immediate-release oxycodone for the management of breakthrough pain in opioid-tolerant patients with chronic pain.2011
Efficacy and safety of extended-release, once-daily tramadol in chronic pain: a randomized 12-week clinical trial in osteoarthritis of the knee.2004
Tolerability, Safety, and Quality of Life with Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR in Patients with Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-label, Phase 3b/4 Trial.
Effectiveness of Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR for the Management of Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-Label, Phase 3b/4 Study.2016
Effectiveness and Safety of Tapentadol Prolonged Release (PR) Versus a Combination of Tapentadol PR and Pregabalin for the Management of Severe, Chronic Low Back Pain With a Neuropathic Component: A Randomized, Double-blind, Phase 3b Study.2015
Once-daily, controlled-release tramadol and sustained-release diclofenac relieve chronic pain due to osteoarthritis: a randomized controlled trial.
Risk of adverse events in patients prescribed long-term opioids: A cohort study in the UK Clinical Practice Research Datalink.2019
A randomized study to demonstrate noninferiority of once-daily OROS(®) hydromorphone with twice-daily sustained-release oxycodone for moderate to severe chronic noncancer pain.
A Clinical Trial Comparing Tapering Doses of Buprenorphine with Steady Doses for Chronic Pain and Co-existent Opioid Addiction.2010
A Detailed Exploration Into the Association of Prescribed Opioid Dosage and Overdose Deaths Among Patients With Chronic Pain.2016
Tramadol in post-herpetic neuralgia: a randomized, double-blind, placebo-controlled trial.2003
A 6-months, randomised, placebo-controlled evaluation of efficacy and tolerability of a low-dose 7-day buprenorphine transdermal patch in osteoarthritis patients naïve to potent opioids.2010
A comparison of the analgesic efficacy of Tramadol Contramid OAD versus placebo in patients with pain due to osteoarthritis.2007
Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study.
Efficacy and safety of tapentadol extended release for the management of chronic low back pain: results of a prospective, randomized, double-blind, placebo- and active-controlled Phase III study.2010
Treatment of osteoarthritis pain with controlled release oxycodone or fixed combination oxycodone plus acetaminophen added to nonsteroidal antiinflammatory drugs: a double blind, randomized, multicenter, placebo controlled trial.1999
Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial.2002
Effect of cannabis use in people with chronic non-cancer pain prescribed opioids: findings from a 4-year prospective cohort study.2018
The association of opioid use with incident lower extremity fractures in spinal cord injury.2013
Coronary heart disease outcomes among chronic opioid and cyclooxygenase-2 users compared with a general population cohort.2011
Cebranopadol, a novel first-in-class analgesic drug candidate: first experience in patients with chronic low back pain in a randomized clinical trial.2017
Analgesic tolerance without demonstrable opioid-induced hyperalgesia: a double-blinded, randomized, placebo-controlled trial of sustained-release morphine for treatment of chronic nonradicular low-back pain.2012
Comparative out-of-hospital mortality of long-acting opioids prescribed for non-cancer pain: A retrospective cohort study.2019
Controlled-release oxycodone and naloxone in the treatment of chronic low back pain: a placebo-controlled, randomized study.-- Not Found --
Nonrandomized Intervention Study of Naloxone Coprescription for Primary Care Patients Receiving Long-Term Opioid Therapy for Pain.
Tramadol hydrochloride extended-release once-daily in the treatment of osteoarthritis of the knee and/or hip: a double-blind, randomized, dose-ranging trial.
Prescription opioids for back pain and use of medications for erectile dysfunction.2013
Opioid prescriptions for chronic pain and overdose: a cohort study.2010
The role of opioid prescription in incident opioid abuse and dependence among individuals with chronic noncancer pain: the role of opioid prescription.2014
Primary care-based buprenorphine taper vs maintenance therapy for prescription opioid dependence: a randomized clinical trial.2014
Efficacy and safety of 12 weeks of osteoarthritic pain therapy with once-daily tramadol (Tramadol Contramid OAD).-- Not Found --
Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study.2008
Efficacy and safety of an extended-release oxycodone (Remoxy) formulation in patients with moderate to severe osteoarthritic pain.-- Not Found --
Health-Related Quality-of-Life Outcomes in Patients Treated with Push-Pull OROS Hydromorphone versus Extended-Release Oxycodone for Chronic Hip or Knee Osteoarthritis Pain: A Randomized, Open-Label, Parallel-Group, Multicenter Study.2008
Extended-release tramadol in the treatment of osteoarthritis: a multicenter, randomized, double-blind, placebo-controlled clinical trial.2006
Controlled-release oxycodone and pregabalin in the treatment of neuropathic pain: results of a multicenter Italian study.2009
Morphine, gabapentin, or their combination for neuropathic pain.2005
Combination of morphine with nortriptyline for neuropathic pain.2015
Efficacy and tolerability of buccal buprenorphine in opioid-experienced patients with moderate to severe chronic low back pain: results of a phase 3, enriched enrollment, randomized withdrawal study.2016
Controlled-release oxycodone for pain in diabetic neuropathy: a randomized controlled trial.2003
Pregabalin and the Risk for Opioid-Related Death: A Nested Case-Control Study.2018
Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case-control study.2017
Opioid dose and drug-related mortality in patients with nonmalignant pain.2011
Opioid dose and risk of road trauma in Canada: a population-based study.2013
Buprenorphine transdermal system in adults with chronic low back pain: a randomized, double-blind, placebo-controlled crossover study, followed by an open-label extension phase.
Buprenorphine transdermal system for opioid therapy in patients with chronic low back pain.-- Not Found --
Once-daily OROS hydromorphone ER compared with placebo in opioid-tolerant patients with chronic low back pain.2010
Efficacy and tolerability of once-daily OROS hydromorphone and twice-daily extended-release oxycodone in patients with chronic, moderate to severe osteoarthritis pain: results of a 6-week, randomized, open-label, noninferiority analysis.2007
Tolerability of tapentadol immediate release in patients with lower back pain or osteoarthritis of the hip or knee over 90 days: a randomized, double-blind study.2009
Efficacy and safety of OPANA ER (oxymorphone extended release) for relief of moderate to severe chronic low back pain in opioid-experienced patients: a 12-week, randomized, double-blind, placebo-controlled study.2007
Efficacy and tolerability of a hydrocodone extended-release tablet formulated with abuse-deterrence technology for the treatment of moderate-to-severe chronic pain in patients with osteoarthritis or low back pain.
Efficacy and safety of a hydrocodone extended-release tablet formulated with abuse-deterrence technology in patients with moderate-to-severe chronic low back pain.-- Not Found --
Prolonged-release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients.2008
Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy.
Rates of adverse events of long-acting opioids in a state Medicaid program.2007
Exposure-Response Association Between Concurrent Opioid and Benzodiazepine Use and Risk of Opioid-Related Overdose in Medicare Part D Beneficiaries.2018
Varenicline for opioid withdrawal in patients with chronic pain: a randomized, single-blinded, placebo controlled pilot trial.2015
The effect of opioids on phantom limb pain and cortical reorganization.2001
Gabapentin versus Transdermal Fentanyl Matrix for the Alleviation of Chronic Neuropathic Pain of Radicular Origin: A Randomized Blind Multicentered Parallel-Group Noninferiority Trial.2019
Mortality After Discontinuation of Primary Care-Based Chronic Opioid Therapy for Pain: a Retrospective Cohort Study.2019
Opioid therapy for chronic noncancer back pain. A randomized prospective study.1998
Further validation of an opioid risk assessment tool: the Brief Risk Interview.
Validation of a new risk assessment tool: the Brief Risk Questionnaire.-- Not Found --
Preliminary data on a new opioid risk assessment measure: the Brief Risk Interview.-- Not Found --
A comparison of various risk screening methods in predicting discharge from opioid treatment.2012
Efficacy and safety of low-dose transdermal buprenorphine patches (5, 10, and 20 microg/h) versus prolonged-release tramadol tablets (75, 100, 150, and 200 mg) in patients with chronic osteoarthritis pain: a 12-week, randomized, open-label, controlled, parallel-group noninferiority study.
Morphine sulfate and naltrexone hydrochloride extended release capsules in patients with chronic osteoarthritis pain.2010
A phase 3, multicenter, randomized, double-blind, placebo-controlled, safety, tolerability, and efficacy study of Xtampza ER in patients with moderate-to-severe chronic low back pain.2015
A 12-week, randomized, placebo-controlled trial assessing the safety and efficacy of oxymorphone extended release for opioid-naive patients with chronic low back pain.
Efficacy and safety of controlled-release oxycodone for the management of moderate-to-severe chronic low back pain in Japan: results of an enriched enrollment randomized withdrawal study followed by an open-label extension study.2019
Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain.2007
Codeine plus paracetamol versus paracetamol in longer-term treatment of chronic pain due to osteoarthritis of the hip. A randomised, double-blind, multi-centre study.1990
Tolerability, Safety, and Effectiveness of Oxycodone DETERx in Elderly Patients ≥65 Years of Age with Chronic Low Back Pain: A Randomized Controlled Trial.2017
Comparative mortality among Department of Veterans Affairs patients prescribed methadone or long-acting morphine for chronic pain.2011
Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial.2018
Association of Opioids with Falls, Fractures, and Physical Performance among Older Men with Persistent Musculoskeletal Pain.2016
Tapering off long-term opioid therapy in chronic non-cancer pain patients: A randomized clinical trial.2018
Transdermal fentanyl for improvement of pain and functioning in osteoarthritis: a randomized, placebo-controlled trial.2006
Effectiveness and Safety of Transdermal Buprenorphine Versus Sustained-release Tramadol in Patients With Moderate to Severe Musculoskeletal Pain: An 8-Week, Randomized, Double-Blind, Double-Dummy, Multicenter, Active-controlled, Noninferiority Study.2015
Opioid use for noncancer pain and risk of myocardial infarction amongst adults.2013
Opioid use for noncancer pain and risk of fracture in adults: a nested case-control study using the general practice research database.2013
One Month of Oral Morphine Decreases Gray Matter Volume in the Right Amygdala of Individuals with Low Back Pain: Confirmation of Previously Reported Magnetic Resonance Imaging Results.2016
Analgesic use and risk of recurrent falls in participants with or at risk of knee osteoarthritis: data from the Osteoarthritis Initiative.2017
Opioid medication discontinuation and risk of adverse opioid-related health care events.2019
Treatment of persistent pain associated with osteoarthritis with controlled-release oxycodone tablets in a randomized controlled clinical trial.-- Not Found --
Analgesic efficacy, safety, and tolerability of a long-acting abuse-deterrent formulation of oxycodone for moderate-to-severe chronic low back pain in subjects successfully switched from immediate-release oxycodone.
Oxymorphone extended-release tablets relieve moderate to severe pain and improve physical function in osteoarthritis: results of a randomized, double-blind, placebo- and active-controlled phase III trial.
Efficacy and safety of fulranumab as monotherapy in patients with moderate to severe, chronic knee pain of primary osteoarthritis: a randomised, placebo- and active-controlled trial.2016
Buprenorphine transdermal system and quality of life in opioid-experienced patients with chronic low back pain.2013
The impact of buprenorphine transdermal delivery system on activities of daily living among patients with chronic low back pain: an application of the international classification of functioning, disability and health.2014
Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy.2015
Opioid analgesics and the risk of fractures in older adults with arthritis.2011
A feasibility study of transdermal buprenorphine versus transdermal fentanyl in the long-term management of persistent non-cancer pain.2013
A comparison of common screening methods for predicting aberrant drug-related behavior among patients receiving opioids for chronic pain management.
Randomised trial of oral morphine for chronic non-cancer pain.1996
A randomized, placebo-controlled, double-blinded, parallel-group, 5-week study of buprenorphine transdermal system in adults with osteoarthritis.
Hydromorphone extended release for neuropathic and non-neuropathic/nociceptive chronic low back pain: a post hoc analysis of data from a randomized, multicenter, double-blind, placebo-controlled clinical trial.-- Not Found --
A randomized trial of 2 prescription strategies for opioid treatment of chronic nonmalignant pain.2011
A preliminary study comparing methadone and buprenorphine in patients with chronic pain and coexistent opioid addiction.2013
Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain.2006
Opioid treatment of painful chronic pancreatitis.2000
Tapentadol potentiates descending pain inhibition in chronic pain patients with diabetic polyneuropathy.2014
Tramadol in neuropathic pain after spinal cord injury: a randomized, double-blind, placebo-controlled trial.-- Not Found --
The effectiveness of a weak opioid medication versus a cyclo-oxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug in treating flare-up of chronic low-back pain: results from two randomized, double-blind, 6-week studies.-- Not Found --
Intraindividual differences in pain relief and functional improvement in osteoarthritis with diclofenac or tramadol.1998
All-Cause and Drug-Related Medical Events Associated with Overuse of Gabapentin and/or Opioid Medications: A Retrospective Cohort Analysis of a Commercially Insured US Population.2018
A randomized, double-blind, double-dummy comparison of short- and long-acting dihydrocodeine in chronic non-malignant pain.2014
Double blind randomized placebo control trial of controlled release codeine in the treatment of osteoarthritis of the hip or knee.
Fentanyl buccal tablet (FBT) for relief of breakthrough pain in opioid-treated patients with chronic low back pain: a randomized, placebo-controlled study.2007
Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial.2002
Results of a double-blind, placebo-controlled, fixed-dose assessment of once-daily OROS® hydromorphone ER in patients with moderate to severe pain associated with chronic osteoarthritis.2013
A randomized, open-label, multicenter trial comparing once-a-day AVINZA (morphine sulfate extended-release capsules) versus twice-a-day OxyContin (oxycodone hydrochloride controlled-release tablets) for the treatment of chronic, moderate to severe low back pain: improved physical functioning in the ACTION trial.-- Not Found --
The ACTION study: a randomized, open-label, multicenter trial comparing once-a-day extended-release morphine sulfate capsules (AVINZA) to twice-a-day controlled-release oxycodone hydrochloride tablets (OxyContin) for the treatment of chronic, moderate to severe low back pain.-- Not Found --
A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.2015
Single-entity hydrocodone extended-release capsules in opioid-tolerant subjects with moderate-to-severe chronic low back pain: a randomized double-blind, placebo-controlled study.2014
Efficacy and tolerability of buccal buprenorphine in opioid-naive patients with moderate to severe chronic low back pain.2016
Out-of-hospital mortality among patients receiving methadone for noncancer pain.2015
Prescription of Long-Acting Opioids and Mortality in Patients With Chronic Noncancer Pain.2016
Increased risk of reproductive dysfunction in women prescribed long-term opioids for musculoskeletal pain: A matched cohort study in the Clinical Practice Research Datalink.2018
Management of Neuropathic Chronic Pain with Methadone Combined with Ketamine: A Randomized, Double Blind, Active-Controlled Clinical Trial.2017
Oral opioid therapy for chronic peripheral and central neuropathic pain.2003
Association Between Commonly Prescribed Opioids and Androgen Deficiency in Men: A Retrospective Cohort Analysis.2017
Efficacy of tramadol in treatment of pain in fibromyalgia.2000
Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for the purpose of titrating to stable pain control?1999
Relationship of opioid use and dosage levels to fractures in older chronic pain patients.2010
Prescription Opioid Duration, Dose, and Increased Risk of Depression in 3 Large Patient Populations.-- Not Found --
The influence of prescription opioid use duration and dose on development of treatment resistant depression.2016
Efficacy of tramadol in treatment of chronic low back pain.2000
Safety and efficacy of tapentadol ER in patients with painful diabetic peripheral neuropathy: results of a randomized-withdrawal, placebo-controlled trial.2011
Tapentadol prolonged-release for moderate-to-severe chronic osteoarthritis knee pain: a double-blind, randomized, placebo- and oxycodone controlled release-controlled study.2017
Fentanyl buccal tablet for the relief of breakthrough pain in opioid-tolerant adult patients with chronic neuropathic pain: a multicenter, randomized, double-blind, placebo-controlled study.2007
Transdermal Buprenorphine Relieves Neuropathic Pain: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial in Diabetic Peripheral Neuropathic Pain.2016
Randomized controlled trial of the combined monoaminergic and opioid investigational compound GRT9906 in painful polyneuropathy.2012
The effect of tramadol in painful polyneuropathy in relation to serum drug and metabolite levels.
Efficacy and safety of buprenorphine transdermal system (BTDS) for chronic moderate to severe low back pain: a randomized, double-blind study.2011
Efficacy and safety of the seven-day buprenorphine transdermal system in opioid-naïve patients with moderate to severe chronic low back pain: an enriched, randomized, double-blind, placebo-controlled study.2011
Prescription Opioid Taper Support for Outpatients With Chronic Pain: A Randomized Controlled Trial.2017
Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis.2017
Incident opioid use and risk of hip fracture among persons with Alzheimer disease: a nationwide matched cohort study.2019
Outpatient treatment of prescription opioid dependence: comparison of two methods.1982
A randomized, double-blind, crossover comparison of the efficacy and safety of oral controlled-release tramadol and placebo in patients with painful osteoarthritis.-- Not Found --
Methodological Issues in Conducting Pilot Trials in Chronic Pain as Randomized, Double-blind, Placebo-controlled Studies.2016
Prolonged-release oxycodone-naloxone for treatment of severe pain in patients with Parkinson's disease (PANDA): a double-blind, randomised, placebo-controlled trial.2015
Comparison of two methodologies to measure agricultural occupational fatalities.1990
Quality of life under oxycodone/naloxone, oxycodone, or morphine treatment for chronic low back pain in routine clinical practice.2016
Development of opioid-induced constipation: post hoc analysis of data from a 12-week prospective, open-label, blinded-endpoint streamlined study in low-back pain patients treated with prolonged-release WHO step III opioids.2015
Effectiveness of Opioids for Chronic Noncancer Pain: A Two-Year Multicenter, Prospective Cohort Study With Propensity Score Matching.2019
Associations between medical cannabis and prescription opioid use in chronic pain patients: A preliminary cohort study.2017
A randomized withdrawal, placebo-controlled study evaluating the efficacy and tolerability of tapentadol extended release in patients with chronic painful diabetic peripheral neuropathy.2014
A Phase IIIb, Multicentre, Randomised, Parallel-Group, Placebo-Controlled, Double-Blind Study to Investigate the Efficacy and Safety of OROS Hydromorphone in Subjects with Moderate-to-Severe Chronic Pain Induced by Osteoarthritis of the Hip or the Knee.2011
Analgesic efficacy and safety of oxycodone in combination with naloxone as prolonged release tablets in patients with moderate to severe chronic pain.2008
Post hoc analysis of a randomized, double-blind, placebo-controlled efficacy and tolerability study of tramadol extended release for the treatment of osteoarthritis pain in geriatric patients.2007
Evaluation of study discontinuations with tapentadol inmmediate release and oxycodone immediate release in patients with low back or osteoarthritis pain.-- Not Found --
Extended-release tramadol (tramadol ER) in the treatment of chronic low back pain.-- Not Found --
Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia.1998
Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy.2003
Oxytrex minimizes physical dependence while providing effective analgesia: a randomized controlled trial in low back pain.2006
Fentanyl buccal tablet compared with immediate-release oxycodone for the management of breakthrough pain in opioid-tolerant patients with chronic cancer and noncancer pain: a randomized, double-blind, crossover study followed by a 12-week open-label phase to evaluate patient outcomes.2013
Predicting aberrant behaviors in opioid-treated patients: preliminary validation of the Opioid Risk Tool.-- Not Found --
A multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of single-entity, once-daily hydrocodone tablets in patients with uncontrolled moderate to severe chronic low back pain.2015
Long-term safety and tolerability of tapentadol extended release for the management of chronic low back pain or osteoarthritis pain.-- Not Found --
Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebo-controlled, crossover trial.2008
A randomized, placebo-controlled study of the impact of the 7-day buprenorphine transdermal system on health-related quality of life in opioid-naïve patients with moderate-to-severe chronic low back pain.2013
A Subgroup Analysis Found no Diminished Response to Buprenorphine Transdermal System Treatment for Chronic Low Back Pain Patients Classified with Depression.2016
Buprenorphine transdermal system compared with placebo reduces interference in functioning for chronic low back pain.2015
A randomized, controlled trial of oxycodone versus placebo in patients with postherpetic neuralgia and painful diabetic neuropathy treated with pregabalin.2010
Tramadol for the treatment of joint pain associated with osteoarthritis: a randomized, double-blind, placebo-controlled trial2001
MST continuous tablets and pain control in severe rheumatoid arthritis1991

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