Cognitive Effects of Opioids in Persons with Chronic Non-Cancer Pain

1. Cognitive Effects of Opioids in Persons with Chronic Non-Cancer Pain Scott Strassels, PharmD, BCPS scotts1@u.washington.edu 8/12/02 

2. Acknowledgments • Dr. Jim Robinson • Dr. Dan Carr

3. Goal • To review the current literature for studies of the effects of opioids on cognition, functioning, & health-related quality of life (HRQL) in persons with chronic, non-cancer pain

4. Background • Opioids are associated with drowsiness, decreased ability to perform tasks, falls, difficulties with self-care (Medical Letter 2002;44(1134), Ebly EM et al 1997) • Effects are thought to be dose-dependent, to occur more often in elderly persons, & with drugs that have an active, renally-eliminated metabolite, such as meperidine) • Opioid use in elderly persons was associated with delirium in 3 of 5 prospective studies (Gray et al 1999) • 1 study grouped opioids with other psychoactive drugs

5. Why is this important? • Important to policy makers, clinicians, & patients • Will this make me drowsy? • What can I take at work? • What are the implications for society & chances of treatment success?

6. Methods • Literature search of Medline 1966 - present, Embase 1990 - 2002, PsycInfo 1887 – present, Cochrane Library 2002, Issue 2 • Search Terms: Opioid, cognitive, function, quality of life • Cancer, Substance abuse populations excluded

7. Results • ~300 articles identified • Relatively few papers focus on the cognitive effects of opioids in persons with chronic, non-cancer pain

8. McCracken et al 2001 • Prospective study to assess factors that best predict cognitive complaints • N = 275 consecutive patients, age  18 years, referred to a university pain management center • Excluded persons with history of head trauma or stroke • Participants may have had other types of brain impairment • Participants completed the Beck Depression Inventory (BDI), Pain Anxiety Symptom Scale (PASS), Sickness Impact Profile (SIP)

9. McCracken et al 2001 (continued) • 54% reported  1 problem with cognitive functioning • Most common complaints: forgetfulness (23.4%), minor accidents (23.1%), difficulty finishing tasks (20.5%), difficulty with attention (18.7%) • Significantly associated with cognitive complaints: Use of antidepressants, pain severity, pain-related anxiety, & depression • No measure of perceived severity of cognitive functioning

10. Sjøgren et al 2000 • Goal: To compare neuropsychological performance between chronic, nonmalignant pain patients on stable, long-term opioid therapy & healthy controls • N = 40, median age 60, 16 M, 24 F • Eligible persons: those taking opioids on a fixed time schedule, with a stable daily dose for  14 days • Excluded: users of other psychotropic drugs or alcohol, persons with metabolic disturbances, physical or neurological dysfunction interfering with the test

11. Sjøgren et al 2000 (continued) • Opioids used: SR morphine, methadone, ketobemidone, buprenorphine, tramadol • Daily doses: 15-300 mg morphine (median = 60 mg) or equianalgesic doses of other opioids • Results were compared to 40 healthy, sex- & age-matched volunteers, met exclusion criteria • Testing was delayed for 50-450 minutes after the last dose, done late in the AM

12. Sjøgren et al 2000 (continued) • Tests completed: Continuous Reaction Time (CRT), Finger Tapping Test (FTT), Paced Auditory Serial Audition Test (PASAT), Hospital Anxiety & Depression Scale (HAD), Karnofsky Performance Status Scale (KPS) • CRT measures attention/concentration, FTT measures psychomotor speed, & PASAT measures working memory

13. Sjøgren et al 2000 (continued) • 38% of patients reported anxiety, 50% reported depression • Mean KPS = 70% (cares for self, unable to carry on normal activity or to do normal work • Physician completes the KPS instead of patient • Vigilance/attention, psychomotor speed, and working memory were significantly impaired in patients • Persons on methadone were significantly slower on the FTT using the dominant hand

14. Sjøgren et al 2000 (continued) • Can’t tell if opioids were responsible for neuropsychological performance • Possible to compare to pain patients who were not using opioids?

15. Zacny 1995 • Extensive review of published literature • Morphine • Speed of task performance slows temporarily, but tolerance develops • Accuracy of response, ability to process information, intellectual functioning appear to be less affected • Meperidine • Information is limited, with conflicting results • Anticholinergic effects may contribute to cognitive effects

16. Zacny 1995 (continued) • Fentanyl, alfentanil • Task performance speed is more likely to be impaired than higher level cognitive processes (Digit substitution, learning, memory) • Methadone • At doses of 50-80 mg/day in people on methadone maintenance, published studies show inconsistent effects • Chronic pain patients on lower doses are unlikely to be adversely affected

17. Zacny 1995 (continued) • Codeine • Doses are typically limited due to appearance of adverse effects • Doses used were no more than 50% of the standard analgesic dose of morphine • Even at low doses, some impairment was noted among healthy volunteers

18. Zacny 1995 (continued) • Oxycodone, dihydrocodeine • Data on cognitive effects is limited • Oxycodone is increasingly important due to the popularity of Oxycontin • Oxycodone is approximately equipotent to morphine, thus effects might be expected to be similar

19. Zacny 1995 (continued) • Propoxyphene • Motor response appears to be impaired, but not information processing • Unknown if tolerance develops • Long-acting active metabolite may contribute to effects

20. Zacny 1995 (continued) • Conclusions • Overall, opioid users appear to show little if any impairment in laboratory tests • Epidemiological studies suggest no increased risk of accidents or impaired neuropsychological functioning • In healthy volunteers • Cognitive performance is less affected than psychomotor performance • Impairment is more apparent with agonist-antagonists and partial agonists

21. Zacny 1995 (continued) • Concerns about cognitive effects are generally not a contraindication to chronic opioid therapy in persons with chronic, nonmalignant pain

22. What’s Missing? • Research published in languages other than English • Effects of pain, opioid use on health-related quality of life

23. Future Challenges • Separating the effects of disease & treatment • Understanding differences between types of injuries leading to chronic pain • How long do acute effects on cognition & functioning persist? • When does acute become chronic? • How do self-reported complaints correlate with neuropsychological test results & actual performance?