Rates of Opioid Misuse, Abuse, and Addiction in Chronic Pain. Kevin E. Vowles, PhD University of New Mexico

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Rates of Opioid Misuse, Abuse, and Addiction in Chronic Pain Kevin E. Vowles, PhD University of New Mexico 1

Kevin E. Vowles, Disclosures Consultant, Pfizer Independent Grants for Learning and Change, M. D. Sullivan (PI). The contents of will not include discussion of off label or investigative drug uses. The faculty is aware that is their responsibility to disclose this information. 2

Planning Committee, Disclosures AAAP aims to provide educational information that is balanced, independent, objective and free of bias and based on evidence. In order to resolve any identified Conflicts of Interest, disclosure information from all planners, faculty and anyone in the position to control content is provided during the planning process to ensure resolution of any identified conflicts. This disclosure information is listed below: The following developers and planning committee members have reported that they have no commercial relationships relevant to the content of this webinar to disclose: AAAP CME/CPD Committee Members Dean Krahn, MD, Kevin Sevarino, MD, PhD, Tim Fong, MD, Tom Kosten, MD, Joji Suzuki, MD; and AAAP Staff Kathryn Cates-Wessel, Miriam Giles, and Justina Andonian. All faculty have been advised that any recommendations involving clinical medicine must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported, or used in the presentation must conform to the generally accepted standards of experimental design, data collection, and analysis. The content of this CME activity has been reviewed and the committee determined the presentation is balanced, independent, and free of any commercial bias. Speakers must inform the learners if their presentation will include discussion of unlabeled/investigational use of commercial products. 3

Target Audience The overarching goal of PCSS-O is to offer evidence-based trainings on the safe and effective prescribing of opioid medications in the treatment of pain and/or opioid addiction. Our focus is to reach providers and/or providers-in-training from diverse healthcare professions including physicians, nurses, dentists, physician assistants, pharmacists, and program administrators. 4

Educational Objectives At the conclusion of this activity participants should be able to: Define opioid misuse, abuse, and addiction and understand the different patterns of behavior associated with each. State the key deficiencies at present in the opioid use literature as it relates to chronic pain. Identify the range of possible rates of opioid misuse and addiction in chronic pain, while also acknowledging the caveats with these estimates given the current state of the scientific literature. 5

Chronic Pain Common e.g., Breivik et al., 2006, Gureje et al., 1998 0% Adult 0% Population Chronic Pain Persistent e.g., Andersson, 2004; Elliott et al., 2002 Gureje et al., 2001 Disabling e.g., Fordyce, 1988; Gatchel et al., 2007 12 yr 4 yr 1 yr Pain remains Pain remains Pain remains 0% 20% 40% 60% 80% 100% 6

Figure 7: The impact of chronic pain on daily activities. 27% 47% 43 % 30 % 61% 48% 47% 54% 72% 73% 65% 7

History of Opioid Prescription Prior to mid 1980 s, restricted for surgery, recovery from severe injury, or end of life. Porter and Jick (1980, New England Journal of Medicine) Portenoy & Foley (1986; Pain) - case series 38 patients on opioids followed for > 7 yrs 24 patients reported adequate pain relief No systematic dose increase over the years 2 patients (both with a h/o substance abuse) had problems 8

Net Result 1: Explosion of Opioid Use From: Volkow, 29 April 2014 Presentation to Congress. IMS Health, National Prescription Audit, Years 1997-2013. www.drugabuse.gov/aboutnida/legislative-activities/testimony-to-congress/2015/prescription-opioidheroin-abuse 9

Specifically in Chronic Pain +400% +100% 10

Net Result 2: Explosion of Opioid-Related Problems 11

Conclusions thus far: Rates of opioid prescriptions have increased over the past three decades. Increased rates of problematic opioid use and impact have tracked this increase in prescription. Problem: We still do not know the scope of the problem in chronic pain... 12

Defining the scope: Højsted & Sjøgren (2007). Addiction to opioids in chronic pain patients: A literature review. Eur J Pain 0% to 50% Martell et al. (2007). Opioid treatment for chronic back pain: Prevalence, efficacy, and association with addiction. Ann Int Med 3% to 43% 13

Potential Source of Poor Precision Terminology Misuse, abuse, addiction, aberrant use, dependence, nonmedical or nontherapeutic use, physical dependence, psychological dependence, and pseudoaddiction. e.g., O Connor et al. (2013), Pain; Smith at al. (2013), Pain; Webster & Fine (2010), J Pain. Other potential sources of heterogeneity differences in study methods (design, assessment method, etc.), sample size, & study quality. 14

Present Review Purpose: Clarify/Refine current estimates regarding rates of problematic (prescribed) opioid use in chronic pain. Coded for different patterns of use: Misuse: not using as prescribed; harm neutral Abuse: purposeful use for sedation or euphoria Addiction: use associated with demonstrated or marked potential for harm Study methods were recorded: Design, Setting, Method of Assessment, Study Purpose* *No differences indicated* Vowles, McEntee, Siyahhan Julnes, Frohe, Ney, & van der Goes. (2015). Pain 15

To increase precision in estimates: Estimates were weighted by: Raw Sample Size Log Sample Size Winsorized Sample Size Quality (0-8; based on Chou et al., 2009) >5 quality = High Quality Log Sample Size x Quality* 16

Search Strategy Search terms <chronic pain> + <opioid (+ synonyms)> + <1+ opioid use terms> Inclusion/Exclusion Criteria Adults Chronic non-cancer pain Oral opioids Abstract listed 1+ of use terms Quantitative information provided regarding use 17

Information Flow Figure from: Vowles et al. (2015). Pain 18

Overall Results 29 studies reported on rates of misuse 12 studies reported on rates of addiction 1 study reported on rates of abuse (8% - Study quality 8/8) Data extraction... Sample Size Study Methods Minimum/Maximum Rates Quality Rating 19

Table from: Vowles et al. (2015). Pain 20

Opioid Misuse Results Minimum Maximum Mean (SD) 95% CI Mean (SD) 95% CI Unweighted 28.1% (22.9%) 19.8% - 36.4% 29.3% (22.5%) 21.1% - 37.5% Weighted means: Sample Size 69.4% (19.1%) 62.4% - 76.4% 69.5% (19.1%) 62.5% - 76.5% Log Sample Size 27.4% (24.5%) 18.5% - 36.3% 28.4% (24.1%) 19.6% - 37.2% Winsorized 21.7% (24.2%) 12.9% - 30.5% 22.6% (24.1%) 13.8% - 31.4% Quality Rating 25.2% (18.9%) 18.3% - 32.1% 26.4% (18.7%) 19.6% - 33.2% Sample Size x Quality 23.8% (20.6%) 16.3% - 31.3% 24.9% (20.4%) 17.5% - 32.3% Quality: High Quality Studies 23.6% (16.4%) 14.7% - 32.5% 24.5% (16.2%) 15.7% - 33.3% Low Quality Studies 31.8% (31.2%) 16.5% - 47.1% 33.2% (30.3%) 18.4% - 48.0% 21

Opioid Addiction Results Minimum Maximum Mean (SD) 95% CI Mean (SD) 95% CI Unweighted 10.9% (9.8%) 5.3% - 16.5% 11.7% (9.9%) 6.1% - 17.3% Weighted means: Sample Size 4.3% (6.2%) 0.8% - 7.8% 4.7% (6.5%) 1.0% - 8.4% Log Sample Size 10.1% (9.5%) 4.7% - 15.5% 10.8% (9.6%) 5.4% - 16.2% Winsorized 7.8% (8.2%) 3.2% - 12.4% 8.6% (8.3%) 3.9% - 13.3% Quality Rating 10.5% (8.8%) 5.5% - 15.5% 10.4% (8.9%) 5.4% - 15.4% Sample Size x Quality* 9.9% (8.7%) 5.0% - 14.8% 10.7% (8.9%) 5.7% - 15.7% Quality: High Quality Studies 8.8% (7.3%) 4.3% - 13.3% 9.8% (7.8%) 5.0% - 14.6% Low Quality Studies 23.1% (12.9%) 3.4% - 39.2% 23.1% (12.9%) 3.4% - 39.2% 22

Overall Conclusions The literature has some inconsistencies... Raw range observed across studies: Misuse: 0.08% to 81% Addiction: 0.7% to 34.1% Range of methods, study quality, and dispersion of prevalence Some degree of convergence around: Misuse: 21.7%-29.3% (95% CI: 13%-33%) Addiction: 8.8%-10.7% (95% CI: 3%-16%) 23

Utility of opioids? Unclear benefit for long-term pain relief or short-term functional gains High side-effect profile* Potential for misuse/addiction* *Additional treatment requirements 24

Are opioids bad? Understanding what is meant by addiction It is reflective of a pattern of behavior. Shorthand: Physical Effects + Negative Impact = Addiction Also know as Substance Use Disorder 25

Bottom Line in Chronic Pain: Opioids + Physical Effects + Harm = Greater treatment drop-out Poorer treatment outcomes Higher dose = higher distress and disability Resumption of opioid use following a mandatory wean Opioid use alone is not necessarily a problem; Opioid Use Disorder most certainly is a problem. Vowles & Ashworth. (2011). Is opioid withdrawal necessary within comprehensive pain rehabilitation programs? Pain, 152, 10-12. 26

Curious Findings Only three of 38 studies reviewed assessed non-us residents Norway - Misuse: 0.08%-0.3% UK Addiction: 2.8% Denmark Addiction: 14%-19% Prescription Opioid Rates in the: UK (2002-2009) Australia (1992-2012) 27

Morphine & Oxycodone 28

29

8-21 year olds University Hospital system Opioid prescription rates between 2005 and 2014 tallied. Data presented at the 2016 American Pain Society meeting, Austin, TX. 30

Remaining Issues What are the factors contributing to different rates of prescription across countries? Clearly room to clean up the data in this area. Effective treatments for misuse/addiction in those with chronic pain? 31

References Bedson, J., Belcher, J., Martino, O. I., Ndlovu, M., Rathod, T., Walters, K., Jordan, K. P. (2013). The effectiveness of national guidance in changing analgesic prescribing in primary care from 2002 to 2009: An observational database study. European Journal of Pain, 17, 434 443. Blanch, B., Pearson, S.-A., & Haber, P. S. (2014). An overview of the patterns of prescription opioid use, costs and related harms in Australia. British Journal of Clinical Pharmacology, 78(5), 1159 1166. Højsted, J., & Sjøgren, P. (2007). Addiction to opioids in chronic pain patients: a literature review. European Journal of Pain, 11, 490 518. Martell, B., O Connor, P., Kerns, R., Becker, W., Morales, K., Kosten, T., & Fiellin, D. (2007). Opioid treatment for chronic back pain: Prevalence, efficacy, and association with addiction. Annals of Internal Medicine, 146, 187 192. O Connor, A. B., Turk, D. C., Dworkin, R. H., Katz, N. P., Colucci, R., Haythornthwaite, J. a, Zacny, J. P. (2013). Abuse liability measures for use in analgesic clinical trials in patients with pain: IMMPACT recommendations. Pain, 154, 2324 2334. Portenoy, R. K., & Foley, K. M. (1986). Chronic use of opioid analgesics in nonmalignant pain: Report of 38 cases. Pain, 25, 171 186. 32

References Porter, J., & Jick, H. (1980). Addiction in rare in inpatients treated with narcotics. New England Journal of Medicine, 302, 123. Smith, S. M., Dart, R. C., Katz, N. P., Paillard, F., Adams, E. H., Comer, S. D., Dworkin, R. H. (2013). Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations. Pain, 154, 2287 2796. Sullivan, M. D., Edlund, M. J., Fan, M.-Y., Devries, A., Brennan Braden, J., & Martin, B. C. (2008). Trends in use of opioids for non-cancer pain conditions 2000-2005 in commercial and Medicaid insurance plans: The TROUP study. Pain, 138, 440 449. Vowles, K. E., & Ashworth, J. (2011). Is opioid withdrawal necessary within comprehensive pain rehabilitation programs? Pain, 152, 10 12. Vowles, K. E., McEntee, M. L., Siyahhan, P., Frohe, T., Ney, J. P., & van der Goes, D. N. (2015). Rates of opioid misuse, abuse, and addiction in chronic pain : A systematic review and data synthesis. Pain, 156, 569 576. Webster, L. R., & Fine, P. G. (2010). Approaches to improve pain relief while minimizing opioid abuse liability. Journal of Pain, 11, 602 611. 33

PCSS-O Colleague Support Program and Listserv PCSS-O Colleague Support Program is designed to offer general information to health professionals seeking guidance in their clinical practice in prescribing opioid medications. PCSS-O Mentors comprise a national network of trained providers with expertise in addiction medicine/psychiatry and pain management. Our mentoring approach allows every mentor/mentee relationship to be unique and catered to the specific needs of both parties. The mentoring program is available at no cost to providers. For more information on requesting or becoming a mentor visit: www.pcss-o.org/colleague-support Listserv: A resource that provides an Expert of the Month who will answer questions about educational content that has been presented through PCSS-O project. To join email: pcss-o@aaap.org. 34

PCSS-O is a collaborative effort led by American Academy of Addiction Psychiatry (AAAP) in partnership with: Addiction Technology Transfer Center (ATTC), American Academy of Neurology (AAN), American Academy of Pain Medicine (AAPM), American Academy of Pediatrics (AAP), American College of Physicians (ACP), American Dental Association (ADA), American Medical Association (AMA), American Osteopathic Academy of Addiction Medicine (AOAAM), American Psychiatric Association (APA), American Society for Pain Management Nursing (ASPMN), International Nurses Society on Addictions (IntNSA), and Southeast Consortium for Substance Abuse Training (SECSAT). For more information visit: www.pcss-o.org For questions email: pcss-o@aaap.org Twitter: @PCSSProjects Funding for this initiative was made possible (in part) by Providers Clinical Support System for Opioid Therapies (grant no. 5H79TI025595) from SAMHSA. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department 35 of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.

Thanks for your attention Acknowledgements: Robert Wood Johnson, Center for Health Research NIH (NCCIH): R34AT008398, R21AT007939 Arthritis Research UK Pfizer Independent Grants for Learning and Change Co-authors and manuscript reference: Mindy McEntee, Peter Siyahhan-Julnes, Tessa Frohe, John Ney, David van der Goes Rates of opioid misuse, abuse, and addiction in chronic pain: A systematic review and data synthesis. Pain 2015, 156, 569 576. Questions? kvowles@unm.edu 36