So You Prescribed Suboxone: Do Patients Really Take It? Discussion of Patient Adherence to Suboxone/Burprenorphine Regimens Teresa Hudson, PharmD, PhD Associate Professor, Department of Psychiatry CE Credits: TEXT: 501-406-0076  Activity Code: 29473-24581

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Objectives Discuss importance of buprenorphine adherence Discuss current data on rates of adherence to buprenorphine regimens and identify factors that influence adherence Compare data on buprenorphine adherence to data on medication adherence for other chronic diseases Identify strategies that may be helpful in assessing and improving adherence

Buprenorphine - opioid medication Unique because it is a partial agonist : Less euphoria and physical dependence Lower potential for abuse Used primarily to treat opioid use disorder Other medication assisted treatments (MAT) for OUD include: methadone and extended release naltrexone Typically used as chronic medication Available in multiple dosage forms (buprenorphine only): Injectable Sublingual tablet Buccal film Transdermal patch Intradermal implant Combined with naloxone Sublingual film or tablet Brand names: Bunavail, Suboxone, Zubsolve Can be prescribed by a physician/nurse practitioner/physician’s assistant who have received an FDA Waiver

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MAT decreases mortality among individuals with OUD: Data from 21 Pooled Studies All Cause Mortality Rate per 100 person years Ma et al Molecular Psychiatry 2018

MAT decreases mortality from overdose among individuals with OUD: Data from 16 pooled Studies Overdose Mortality Rate per 100 person years Ma et al Molecular Psychiatry 2018

MAT-specific Mortality rates All Cause Mortality Rate per 100 person years Ma et al Molecular Psychiatry 2018

Buprenorphine may improve neuropsychological function among individuals with OUD? Small study of 20 adults with OUD who were treated with buprenorphine/naloxone All were newly prescribed buprenorphine/naloxone Buprenorphine induction at a community-based clinic then maintained on 4-16 mg of buprenorphine/naloxone x 6 months Neuropsychological testing at baseline and six months assessed: Depressive symptoms Buprenorphine-naloxone adherence Substance use disorder Neuropsychological functioning

Results: Population Characteristics M(SD) or % (n) Range Female 29% (5) Race: Hispanic/Latino/a African American Missing Non-Hispanic White 55% (11) 25% (5) 15% (3) 5% (1) Age 45.2 (8.1) 32-61 Years of Education 11.7 (2.3) 7-18 WRAT-reading subtest 86.9 (14.0) HIV positive BDI-II total score 13.2 (9.2) 0-29.5 % adherence 91.4 (11.8) 64-100 Scott et al substance Abuse treatment Prevention, and Policy 2017

Change in Depressive Symptoms and Neuropsychological (NP) Functioning Time 1 T-score M(SD) Time 2 T Score M(SD) Change Score M(SD) NP Domains Global 41.8 (6.4) 44.5 (6.2) −.01 (.46) Learning 36.2 (11.7) 37.8 (9.3) −.22 (.50) Memory 36.9 (12.2) 38.5 (11.4) −.12 (.89) Verbal Fluency 46.3 (9.0) 47.3 (12.0) −.13 (.94) Processing Speed Attention/Working Memory 44.3 (8.0) 46.9 (9.2) . 04 (.98) Motor 39.2 (9.9) 42.9 (9.0) .09 (.68) Executive Function 41.7 (6.7) 46.2 (8.8) . .41 (.92) Depressive Sx No Change

Key findings No significant change overall baseline compared with follow up for NP or depressive symptoms Correlation between greater adherence to buprenorphine/naloxone and : improved learning (r=.52, p=.019) Improved Memory (r=.59, p=.006) Improved global functioning (r=.6, p=.008) Scott et al substance Abuse treatment Prevention, and Policy 2017

Buprenorphine may decrease healthcare utilization and costs among people with OUD Analyses from claims from commercially insured and Medicaid recipients 2008-2014 Adherence was based on proportion of days covered (PDC) Full adherence was defined as filling buprenorphine prescriptions to cover 80% of the 1 year observation period for each patient PDC= Sum of days supply in 12 month observation period 365 Overall Adherence Rate: 37.1 Commercial Cohort PDC >/=.8 41.3 Medicaid cohort PDC >/=.8 Ronquest et al substance abuse and rehabilitation 2018

Commercial Cohort Characteristics n=16,085 Age, mean (SD) 32.9 (12.7) Sex, n (%) Male Female 10,093 (62.7% 5992 (37.3%) Rural/urban n(%) Urban Rural Unknown 13,828 (86.0%) 2,102 (13.1%) 155 (1.0%) Insurance type Comprehensive/Indemnity EPO/PPO POS/POS with capitation HMO CDHP/HDHP Other/Unknown 476 (3.0%) 9,394 (58.4%) 1,718 (10.7%) 2,407 (15.0%) 954 (5.9%) 1,136 (7.1%) Pre-index comorbid conditions n(%) Non-opioid drug use disorder Alcohol use disorder Depressive Disorder 4,566 (28.4%) 1,753 (10.9%) 4,711 (29.3%) Ronquest et al substance abuse and rehabilitation 2018

Service utilization: Commercial Cohort Ronquest et al substance abuse and rehabilitation 2018 * P<.001

Healthcare Costs: Commercial Cohort Ronquest et al substance abuse and rehabilitation 2018 * P<.001

Factors associated with buprenorphine adherence Ronquest et al substance abuse and rehabilitation 2018

Other Factors Associated with Adherence to Buprenorphine: Race: Some studies suggest that black race may be associated with non-adherence or discontinuation even when among patients who have similar insurance coverage Physical Health Higher levels of physical health comorbidities may be associated with non-adherence or discontinuation MH and SUD comorbidities Depression and bipolar disorder - increased severity Comorbid non-opioid sud - particularly alcohol Buprenorphine dose: At least two studies have found that lower buprenorphine dose is associated with lower levels of adherence Severity of opioid withdrawal symptoms One study examined this in pregnant women and found that more severe withdrawal symptoms were associated with greater risks of non-adherence

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Chronic PH Medications Factors associated with non-adherence Buprenorphine Adherence Rate: 30-40% Chronic PH Medications Adherence rate: 25-50% Severity of MH symptoms Y Physical Health Comorbidities Race Health Literacy ? Complexity of treatment regimen Physician factors Rural residence varies Geographic Region unclear Comparison with Physical Health Medication Adherence

Additional References Brown MT, Bussell JK. Mayo Clinic Proceedings 2011;886(4):304-314 Coker JL, Catlin D, Ray-Griffith S, Knight B, Stowe ZN. Drug and Alcohol Dependence 2018 192:146-149 Kumari S, Manalai P, Leong S, Wooditch A, Mansoor M, Lawson W. The American Journal on Addictions 2016 25:110-117 Litz M, Leslie D. The American Journal on Addictions 2017 26:859-863 Manhapra A, Petrakis I, Rosenheck R. American Journal on Addictions 2017 26:572-280 Ronquest NA, Willson TM, Montejano LB, Nadipelli VR, Wollschlaeger BA. Substance Abuse and Rehabilitation 2018:9, 59-78

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