Neuropsychological Sequelae of
Long Term Opioid Therapy in Chronic Pain Patients
Overview:
Opioid analgesics are commonly used to treat chronic pain in a variety of clinical populations. It is important to create an appropriate balance between analgesia (pain relief) and the side effects of long-term opioid therapy. At its most severe, long-term opioid therapy can cause delirium and opioid-induced sedation, which can lead to coma and respiratory depression (Jarzyna et al., 2011). Additionally, long-term opioid therapy has a heterogeneous effect on attention and higher cortical functioning in chronic pain patients. Current research on the neuropsychological sequelae of long-term opioid therapy has focused primarily on populations with cancer or with substance use disorders. Equivocal results have been found from the limited literature conducted in chronic nonmalignant pain patients. Chronic nonmalignant pain is defined as pain not due to cancer that lasts for three months or more. It can begin with a trauma (e.g., bone fracture, back strain) or medical condition (e.g., pancreatitis, fibromyalgia, migraine; International Society for the Study of Pain, 1994).
Results from current evidenced based studies on the neuropsychological sequelae of long-term opioid therapy in chronic nonmalignant pain patients are still inconclusive due to several limitations and inconclusive results. Randomized controlled trials (Jamison et al., 2003; Rowbotham et al., 2003) and comparative studies (Haythornthwaite & Menefee, 1998; Tassain et al., 2003) reported improvements and/or stable functioning in information processing, memory, attention, psychomotor speed, and manual dexterity following long-term opioid therapy. However, four observational outcome studies found chronic nonmalignant pain patients on long-term opioid therapy had worse attention, vigilance, working memory, psychomotor speed, and/or sustained attention when compared to healthy controls or chronic nonmalignant pain patients not on opioids (Byas-Smith, Chapman, Reed, & Cotsonis, 2005; Gaertner et al., 2006; Sjøgren, Christrup, Petersen, & Hojsted, 2005). Lastly, unrelieved pain and pain-related interference (e.g., psychological distress, physical disability) may also impact attention and thus confound the individual effect of long-term opioid therapy on cognition (Kendall et al., 2010; Tassain et al., 2003).
Abstract: Neuropsychological consequences of chronic opioid use: A quantitative review and meta-analysis (2012).
Introduction: It is widely assumed within the accumulated literature that neuropsychological function is commonly impaired as a consequence of chronic opioid use. Method: Quantitative and systematic review of the literature on the neuropsychology of chronic opioid use using the meta-analysis of observational studies in epidemiology (MOOSE) and the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Results: This meta-analysis suggests that chronic opioid exposure is associated with deficits across a range of different neuropsychological domains. However, the only domains where meta-analysis suggests robust impairment were those of verbal working memory, cognitive impulsivity (risk taking) and cognitive flexibility (verbal fluency). The magnitude of effect across these cognitive domains was medium according to Cohen’s benchmark criteria. Discussion: This analysis highlighted methodological problems present in the literature used and the value of utilising meta-analytic techniques to help further elucidate the neuropsychological consequences of chronic opioid use from ‘core’ addiction phenotypes.
Baldacchinoa, A., Balfoura, D.J.K., Passetti, F., Humphrisc, G., & Matthews, K. (2012). Neuropsychological consequences of chronic opioid use: A quantitative review and meta-analysis. Neuroscience & Behavioral Reviews, 36(9), 2056-2068: http://www.ncbi.nlm.nih.gov/pubmed/22771335
Webinars:
Additional Reading:
Opioid analgesics are commonly used to treat chronic pain in a variety of clinical populations. It is important to create an appropriate balance between analgesia (pain relief) and the side effects of long-term opioid therapy. At its most severe, long-term opioid therapy can cause delirium and opioid-induced sedation, which can lead to coma and respiratory depression (Jarzyna et al., 2011). Additionally, long-term opioid therapy has a heterogeneous effect on attention and higher cortical functioning in chronic pain patients. Current research on the neuropsychological sequelae of long-term opioid therapy has focused primarily on populations with cancer or with substance use disorders. Equivocal results have been found from the limited literature conducted in chronic nonmalignant pain patients. Chronic nonmalignant pain is defined as pain not due to cancer that lasts for three months or more. It can begin with a trauma (e.g., bone fracture, back strain) or medical condition (e.g., pancreatitis, fibromyalgia, migraine; International Society for the Study of Pain, 1994).
Results from current evidenced based studies on the neuropsychological sequelae of long-term opioid therapy in chronic nonmalignant pain patients are still inconclusive due to several limitations and inconclusive results. Randomized controlled trials (Jamison et al., 2003; Rowbotham et al., 2003) and comparative studies (Haythornthwaite & Menefee, 1998; Tassain et al., 2003) reported improvements and/or stable functioning in information processing, memory, attention, psychomotor speed, and manual dexterity following long-term opioid therapy. However, four observational outcome studies found chronic nonmalignant pain patients on long-term opioid therapy had worse attention, vigilance, working memory, psychomotor speed, and/or sustained attention when compared to healthy controls or chronic nonmalignant pain patients not on opioids (Byas-Smith, Chapman, Reed, & Cotsonis, 2005; Gaertner et al., 2006; Sjøgren, Christrup, Petersen, & Hojsted, 2005). Lastly, unrelieved pain and pain-related interference (e.g., psychological distress, physical disability) may also impact attention and thus confound the individual effect of long-term opioid therapy on cognition (Kendall et al., 2010; Tassain et al., 2003).
Abstract: Neuropsychological consequences of chronic opioid use: A quantitative review and meta-analysis (2012).
Introduction: It is widely assumed within the accumulated literature that neuropsychological function is commonly impaired as a consequence of chronic opioid use. Method: Quantitative and systematic review of the literature on the neuropsychology of chronic opioid use using the meta-analysis of observational studies in epidemiology (MOOSE) and the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Results: This meta-analysis suggests that chronic opioid exposure is associated with deficits across a range of different neuropsychological domains. However, the only domains where meta-analysis suggests robust impairment were those of verbal working memory, cognitive impulsivity (risk taking) and cognitive flexibility (verbal fluency). The magnitude of effect across these cognitive domains was medium according to Cohen’s benchmark criteria. Discussion: This analysis highlighted methodological problems present in the literature used and the value of utilising meta-analytic techniques to help further elucidate the neuropsychological consequences of chronic opioid use from ‘core’ addiction phenotypes.
Baldacchinoa, A., Balfoura, D.J.K., Passetti, F., Humphrisc, G., & Matthews, K. (2012). Neuropsychological consequences of chronic opioid use: A quantitative review and meta-analysis. Neuroscience & Behavioral Reviews, 36(9), 2056-2068: http://www.ncbi.nlm.nih.gov/pubmed/22771335
Webinars:
- National Institutes of Health: Center for Information Technology. Pathways to Prevention Workshop on The Effectiveness and Risks of Long-Term Opioid Treatment of Chronic Pain – Day 1 http://videocast.nih.gov/summary.asp?Live=13894&bhcp=1
- The Physical Medicine and Rehabilitation Podcast. Episode 16: Considerations of Long-term Opioid Therapy for Chronic Pain by Rodger Chou, MD Professor at Oregon Health & Science University. http://pmandrpodcast.libsyn.com/episode-16-considerations-of-long-term-opioid-therapy-for-chronic-pain
Additional Reading:
- Kendall, S.E., Sjøgren, P., Andrucioli de Mattos Pimenta, C., Højsted, J., & Kurita, G.P. (2010). The cognitive effects of opioids in chronic non-cancer pain. Pain, 150, 225– 230. doi:10.1016/j.pain.2010.05.012 http://www.ncbi.nlm.nih.gov/pubmed/20554115
- Mailis-Gagnon, A., Lakha, S.F., Furlan, A., Nicholson, K., Yegneswaran, B., & Sabatowski, R. (2012). Systematic Review of the Quality and Generalizability of Studies on the Effects of Opioids on Driving and Cognitive/Psychomotor Performance. The Clinical Journal of Pain, 28(6), 542-555. Doi:10.1097/AJP.0b013e3182385332. http://www.ncbi.nlm.nih.gov/pubmed/22673489
- McLachlan, A.J., Bath, S., Naganathan, A., Hilmer, S.N., Le Couteur, D.G., Gibson, S.J. & Blyth, F.M. (2011). Clinical pharmacology of analgesic medicines in older people: impact of frailty and cognitive impairment. British Journal of Clinical Pharmacology, 71(3), 351–364. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045544/
- Sabatowski, R., Scharnagel, R., Gyllensva¨rd, A., & Steigerwald, I. (2014). Driving Ability in Patients with Severe Chronic Low Back or Osteoarthritis Knee Pain on Stable Treatment with Tapentadol Prolonged Release: A Multicenter, Open-label, Phase 3b Trial. Pain Therapy, 3, 17-29. DOI: 10.1007/s40122-014-0025-3. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4108021/
- Schiltenwolf, M., Akbar, M., Hug, A., Pfüller, U., Gantz, S., Neubauer, E., Flor, H. & Wang, H. (2014). Evidence of Specific Cognitive Deficits in Patients with Chronic Low Back Pain under Long-Term Substitution Treatment of Opioids. Pain Physician; 17:9-19. http://www.ncbi.nlm.nih.gov/pubmed/24452649
Contributor:
Elyssa Scharaga, M.A. – Ferkauf Graduate School of Psychology, Yeshiva University
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