CLINICAL GUIDELINE FOR THE USE OF CHRONIC OPIOID THERAPY IN CLINICAL GUIDELINE FOR THE USE OF CHRONIC OPIOID THERAPY IN GUIDELINE FOR THE Use of Chronic Opioid Therapy in Chronic Noncancer Pain CHRONIC NONCANCER PAIN Evidence Review The American Pain Society in Conjunction with The American Academy of Pain Medicine EVIDENCE REVIEW APS-AAPM Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain TABLE OF CONTENTS Page Introduction 1 Purpose of evidence review ...................................................................... 1 Background 1 Previous guidelines ................................................................................... 2 Scope of evidence review 3 Key questions............................................................................................ 3 Populations................................................................................................ 7 Interventions.............................................................................................. 8 Outcomes.................................................................................................. 8 Conflict of interest............................................................................................. 10 Methods 10 Literature search and strategy................................................................... 10 Inclusion and exclusion criteria.................................................................. 11 Data extraction and synthesis ................................................................... 12 Systematic reviews ................................................................................ 12 Randomized trials on benefits and harms of interventions..................... 12 Observational studies on benefits and harms of interventions............... 14 Studies of risk prediction and diagnostic test accuracy.......................... 14 Dual review................................................................................................ 16 Assessing research applicability and clinical relevance (including magnitude of benefits and harms) ............................................................. 16 Rating a body of evidence......................................................................... 17 Results 19 Size of literature reviewed ......................................................................... 19 Quality of included systematic reviews evaluating efficacy of opioids for chronic noncancer pain and randomized trials......................... 19 Research applicability................................................................................ 19 Key Questions 20 Key Question 1a. In patients being considered for opioids for chronic noncancer pain, how accurate are patient features or characteristics for predicting benefits of chronic opioid therapy? .............. 20 American Pain Society i EVIDENCE REVIEW APS-AAPM Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain TABLE OF CONTENTS Page Key Question 1b. In patients being considered for opioids for chronic noncancer pain, how accurate are patient features or characteristics for predicting opioid-related harms? .................................. 22 Key Question 1c. In patients being considered for opioids for chronic noncancer pain, how accurate are patient features or characteristics for predicting aberrant drug-related behaviors?................. 24 Key Question 2. In patients being considered for opioids for chronic noncancer pain, how accurate are formal screening instruments for predicting benefits of opioid therapy, harms, or aberrant drug-related behaviors? .............................................................. 25 Key Question 3. In patients being considered for opioids for chronic noncancer pain, how effective is risk assessment for: a. Improving clinical outcomes?............................................................. b. Reducing risk of aberrant drug behaviors?........................................ 30 Key Question 4. What are the benefits (including long-term benefits) of opioids for chronic noncancer pain? ....................................... 31 Key Question 5. What are the harms (including long-term harms) of opioids for chronic noncancer pain? In patients at higher risk for abuse or addiction? ................................................................................... 41 Findings: Short-term adverse events .................................................... 42 Findings: Long-term adverse events, aberrant drug-related behaviors, endocrinologic adverse events, and falls/fractures............... 48 Findings: Other data on harms ............................................................. 49 Key Question 6. What are the benefits and harms of opioids for noncancer pain in patients with a history of substance abuse or addiction that are undergoing treatment for addiction? ............................. 51 Key Question 7. What are the comparative benefits and harms of different opioids and different formulations of opioids for chronic noncancer pain?........................................................................................ 52 Findings: Comparisons between one opioid and another opioid........... 53 Findings: Comparisons between sustained-release and immediate-release formulations of opioids or tramadol ......................... 58 Findings: Comparisons between tramadol versus opioids.................... 60 American Pain Society ii EVIDENCE REVIEW APS-AAPM Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain TABLE OF CONTENTS Page Key Question 8. Do the comparative benefits and harms of opioids vary in subpopulations defined by demographics (e.g. age, gender, race), specific underlying pain conditions, or co-morbidities (e.g. liver disease, renal disease, respiratory disease, heart disease, HIV, drug misuse, cancer survivors)?........................................................ 61 Key Question 9. How effective are different strategies for minimizing or treating opioid-related adverse events? .............................. 62 Key Question 10. How does initial or chronic use of opioids impact driving or work safety?............................................................................... 65 Key Question 11. What are the benefits and harms of different methods for initiating and titrating opioids for chronic noncancer pain? .... 68 Key Question 12. What are the benefits and harms of round-the- clock versus as needed dosing of opioids, or round-the-clock with as needed dosing versus as needed dosing alone for chronic noncancer pain? ......................................................................................................... 70 Key Question 13. What are the benefits and harms of regular intramuscular, subcutaneous, intranasal, buccal, or rectal versus oral or transdermal administration of opioids for chronic noncancer pain? ......................................................................................................... 71 Key Question 14. What are the comparative benefits of different strategies for treating acute exacerbations of pain or a new acute pain problem in patients on chronic opioids for chronic noncancer pain? ......................................................................................................... 72 Key Question 15. What are the benefits and harms of opioid rotation versus continued treatment or dose escalation with the same opioid in patients with chronic noncancer pain? .............................. 74 Key Question 16. What are the benefits and harms of different methods for switching patients on opioids for chronic noncancer pain from one opioid to another?............................................................... 75 Key Question 17. How accurate are patient characteristics or features for predicting lack of response to high doses of opioids for chronic noncancer pain? ........................................................................... 76 Key Question 18. How do dose-related responses for opioids change at different dose ranges or with long-term use?............................ 76 Key Question 19. What are the benefits and harms of high (>200 mg/day of morphine or equivalent) versus lower doses of opioids for chronic noncancer pain? ...................................................................... 77 American Pain Society iii EVIDENCE REVIEW APS-AAPM Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain TABLE OF CONTENTS Page Key Question 20. Are high doses of opioids associated with different or unique harms compared to lower doses?................................ 77 Key Question 21. How effective are patient education methods or clinician advice for improving outcomes associated with chronic opioid therapy?.......................................................................................... 78 Key Question 22. How effective is co-prescription with other pain- attenuating medications or combining opioids for improving pain control or decreasing adverse events associated with opioid analgesics?................................................................................................ 79 Key Question 23. What is the effect of concomitant use of drugs with CNS effects on adverse events associated with opioids for chronic noncancer pain? ........................................................................... 82 Key Question 24. What are the benefits associated with