1. 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

2. No conflicts to disclose
Disclosure
No conflicts to disclose

4. 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

5. Opioid-dependence is a major concern for the people of Ontario
Opioid-overdose is the number one cause of mortality in 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

7. 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

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

9. 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

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

11. 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

12. 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

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

14. 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 ( )

15. 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

16. 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

17. 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 ( )
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 ( )
67.3 ( )
65.0 ( )
62.3 ( )

18. 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
UDS -
464
237 (51.1)
0.93
0.86
BZD Rx -
219
70 (32.0)
0.42
0.38
2801
1481 (52.9)
1.00