Joseph K. Eibl, PhD Lisbon; October 2017 Evaluating the impact of prescribed versus non-prescribed benzodiazepine use in opioid substitution therapy: Results from a population-based retrospective cohort study . Joseph K. Eibl, PhD Lisbon; October 2017

No conflicts to disclose Disclosure No conflicts to disclose

Institute for Clinical Evaluative Sciences Ontario is largest single payer system in the North America Located at Sunnybrook Hospital Identified as a global leader in health systems research Data repository for Ontario Health System and Patient Registry data Platform to facilitate access to data and expertise for health systems inquiry

Opioid-dependence is a major concern for the people of Ontario Opioid-overdose is the number one cause of mortality in 24-35 year-olds in Ontario Opioid Agonist Therapy (substitution/maintenance) is the standard of care Number of Ontario patients in methadone/buprenorphine therapy increased from 6000 (2004) to over 50,000 in 2016

Benzodiazepine Use in Patients Enrolled in opioid agonist therapy Benzodiazepines (BZD): class of psychoactive drugs used to treat insomnia, anxiety, seizures, and acute alcohol withdrawal Commonly used by patients in OAT BZD use puts OAT patients at greater risk of overdose and death In Ontario, 59.5% of opioid-related deaths also involve BZD

Purpose Evaluate the impact of prescribed benzodiazepines on patients enrolled in opioid agonist therapy

Categorizing Benzodiazepine Use Four categories based on BZD use Defined BZD use as >30% urine drug screens positive for BZD Defined Rx +/- as having a Rx for from a licensed physician in Ontario

Study Cohort Jan 1, 2006 – Jun 30, 2012 3692 patients initiating opioid agonist therapy N= 208 BZD Rx + / UDS + N= 219 BZD Rx - / UDS + N= 464 BZD Rx + / UDS - N= 2801 BZD Rx - / UDS -

Descriptive Statistics Age (31-37) BZD+/UDS+ were eldest and BZD-/UDS- were youngest Sex (50/50) BZD+/UDS+ were the lowest income quintile Peak Dose Clinically Similar (62-67 mg) across groups

Health System Usage BZD+/USD+ BZD-/UDS- Hospitalizations 0.30 0.10 Psychiatric Hospitalizations 0.27 0.07 Outpatient Primary Care Visits 24 13 Outpatient Psychiatry Visits 3 1 Emergency Department Visits 5.6 2.3

BZD-/UDS+ are 1.6X more likely to discontinue OAT than BZD-/Rx-

Discussion BZD+/UDS+ patients appear to be more complex patient population BZD Rx does not necessarily lead adverse treatment outcomes in MMT patients Overdose related deaths were not remarkable in the study cohort (2006-2012)

Takeaways BZD are involved with >60% of opioid-related overdoses in Ontario, Canada With more potent opioids in the market, we strongly caution judicious monitoring and education for patients being prescribed a BZD during methadone maintenance treatment

Thank You Principal Investigator: Dr. David C Marsh Postdoctoral Fellows: Dr. Joseph K Eibl Postdoctoral Fellow: Dr. Teresa Marsh Physicians: Dr. Mike Franklyn Psychiatry Residents: Dr. Victoria Nguyen, Dr. Kathleen E Anderson, Dr. Nicole Ranger Medical Student: Alex Franklyn PhD Candidates: John Dabous, Kristen Morin Analysts: Graham Gauthier

Table 1 Variable BZD Rx + UDS + UDS - BZD Rx - N = 208 N = 464 N = 219   N = 208 N = 464 N = 219 N = 2801 Age, mean (SD) 37.5 (10.8) 35.5 (11.3) 35.2 (10.7) 31.3 (9.7)  Median (IQR) 37 (28.5-46) 33 (26-44) 33 (27-42) 29 (24-37) Sex Male 104 (50.0) 234 (50.4) 123 (56.2) 1604 (57.3) Female 230 (49.6) 96 (43.8) 1197 (42.7) Income quintile Q1 (lowest) 93 (44.7) 195 (42.0) 77 (35.2) 1031 (36.8) Q2 47 (22.6) 98 (21.1) 47 (21.5) 649 (23.2) Q3 29 (13.9) 83 (17.9) 34 (15.5) 497 (17.7) Q4 23 (11.1) 54 (11.6) 30 (13.7) 337 (12.0) Q5 (highest) 16 (7.7) 33 (7.1) 31 (14.2) 283 (10.1) Health system use Number of hospitalizations mean (SD) 0.30 (0.76) 0.24 (0.79) 0.25 (0.81) 0.14 (0.49) 0 (0-0) Number of psychiatric hospitalizations mean (SD) 0.27 (0.75) 0.22 (0.64) 0.16 (0.49) 0.07 (0.36) Number of GP/FP visits mean (SD) 24.1 (21.6) 19.6 (18.5) 19.5 (22.5) 13.2 (14.0) 19 (10-32) 15 (8-25) 15 (7-23) 9 (4-17) Number of psych visits mean (SD) 3.1 (6.4) 2.1 (4.6) 1.8 (4.6) 1.0 (3.7) 0 (0-3) 0 (0-2) Number of ED visits mean (SD) 5.6 (7.8) 3.9 (7.4) 3.4 (5.4) 2.3 (3.8) 3 (1-8) 2 (0-4.5) 2 (0-4) 1 (0-3) Peak dose mean (SD) 67.0 (31.3) 68.6 (30.5) 63.6 (29.8) 63.7 (27.1) Median (IQR) 67.8 (42.1-91.4) 67.3 (46.6-89.4) 65.0 (37.5-84.8) 62.3 (41.9-83.8)

Table 2 Region Number Patients Number Retained N(%) Unadjusted OR Unadjusted 95% CI Adju sted OR* Adjust ed 95% CI   Primary Outcome: Successful Completion of OAT (ODB eligible) BZD Rx + UDS + 208 96 (46.2) 0.76 0.58-1.01 0.54- 1.05 UDS - 464 237 (51.1) 0.93 0.76-1.13 0.86 0.68- 1.08 BZD Rx - 219 70 (32.0) 0.42 0.31-0.56 0.38 0.27-0.53 2801 1481 (52.9) 1.00