1. Medication Assisted Treatment for SUD: Extended Release Naltrexone Improves Treatment Outcome Desirée A. Crèvecoeur-MacPhail, PhD UCLA Integrated Substance Abuse Program Los Angeles CA California SUD/Health Care Integration Learning Collaborative (ILC) September 24, 2014 1

2. Disclosures No part of this research was funded by Alkermes who manufactures XR-NTX This project was funded solely by the Los Angeles County Department of Public Health Substance Abuse Prevention and Control 2

3. What is Medically Assisted Treatment (MAT)? According to SAMHSA –MAT is the use of medications, in combination with counseling and behavioral therapies, to provide a whole-patient approach to the treatment of substance use disorders –Research shows that when treating substance use disorders, a combination of medication and behavioral therapies is most successful 3

4. Decrease pleasure and reward Have similar structure and bind to same receptor sites as drug of abuse Provide no activation Block full and partial agonists from binding at receptor sites May induce withdrawal symptoms Example: Naltrexone Antagonist Medications 4

5. Naltrexone/XR-NTX for Opioid and Alcohol Dependence Full MU opioid receptor ANTAGONIST No opioid effect 5

6. XR-NTX (Vivitrol) Monthly intramuscular injection Given by nurse, PA, MD, other Non-narcotic, prescribed by MD/DO/NP Not for use if: –Pregnancy –Severe liver disease –Chronic pain requiring opioids 6

7. The LA County Project: Evaluation Background

8. Evaluation Questions 1.Will patients take multiple doses? 2.How did the Urge to Drink/Use score change? 3.Compared to the Post-hoc group, what proportion of the XR-NTX group: Engaged in treatment (LOS 30+ days)? Retained in treatment (LOS 90+ days)?

9. Evaluation Design: Scales & Tools Treatment Outcome Data –Los Angeles County Participant Reporting System (LACPRS) Patient Response to XR-NTX –Medically Assisted Treatment Survey (MATS) –Urge to Drink Scale (UDS) Counselor Attitudes 9

10. Evaluation Design The three medication hubs: –Tarzana Treatment Center (main hub) –Behavioral Health Services –Prototypes Selection criteria: –Infrastructure (staff, examination room, refrigerated and locked location for medication storage) to administer medications –Long-standing histories of providing quality substance abuse treatment to a broad range of clients

11. Evaluation Design: Procedures Three medication hubs were selected based on existing infrastructure. Counselors attended a training. Patients were offered the opportunity to utilize XR- NTX once per month. Data were collected on participants’ urge to use, medication side effects and days of use. Data was collected at weeks 0, 1, 2, 3 post injection and then monthly thereafter.

12. Evaluation Design No random assignment The three medication hubs –Clients went to hubs for medication and returned to their treatment agency for psychosocial treatment Hub selection criteria: –Infrastructure to administer medications –Long-standing histories of providing quality substance abuse treatment

13. Overall Results 13

14. Alcohol (N = 438) Opioid (N = 171) Total (N = 609) Doses Mean (SD)2.81 (2.310)2.41 (1.593)2.70 (2.140) Median222 Maximum169 Total Doses1,2324121,644 Total Injections Received + One Dose Only, % (n)33.8% (148)40.9% (70)35.8% (218) Two Doses Only, % (n)24% (105)19.3% (33)22.7% (138) Three Doses Only, % (n)16% (70)14.6% (25)15.6% (95) Four Doses Only, % (n)11.2% (49)16.4% (28)12.6% (77) Five or More Doses, % (n)15.1% (66)8.8% (15)13.3% (81) + p <.06 Bottom line: Patients received two to three doses of XR-NTX, regardless of substance use disorder. XR-NTX Doses in LA County Among LAC XR-NTX Patients(N=609)

15. Clinical Characteristics (M + SD) XR-NTX Alcohol (N = 438) LAC Alcohol (N = 31,554) XR-NTX Opioid (N = 171) LAC Opioid (N = 18,177) Age40.5 (9.836)38.6 (14.347)36.1 (11.587)40.3 (13.474) Age First used16.7 (5.993)17.7 (6.708)21.8 (9.667)22.1 (8.833) Days Used Past Mo13.5 (11.850)9.8 (11.157)11.1 (12.426)20.6 (12.054) # of Prior Tx Episodes2.4 (5.632)1.2 (3.378)4.2 (5.393)2.7 (4.036) All findings significant at p <.01 Bottom line: XR-NTX recipients appear to have a more substantive SUD history as compared to the typical patient in LA County. Comparison of LAC XR-NTX Patients(N=609)

16. Patient Demographics by Gender Variable Total (N=465) Male (N=223) Female (N=242) Race/Ethnicity* White African American Latino Other a % 45.9 9.7 36.7 7.7 % 43.5 7.2 37.8 11.5 % 48.1 11.9 35.7 4.3 Age at treatment admission37.7 (10.2)38.2 (10.4)37.0 (9.9) Parent of child <age 18**55.142.365.1 Homeless at treatment admission38.137.538.7 Under criminal justice supervision*34.538.929.8 Mental illness diagnosis*46.333.257.9 Prescribed medication for MI**31.620.241.7 16 *p<.05; **p<.01 a Other race/ethnicity includes multi-racial, Native American & Asian Among UCLA XR-NTX Participants (N=465)

17. Reduced Urge to Drink/Use Based on the Urge to Drink/Use Scale, which is scored from 0 to 30. A score of 10 or more indicates danger of relapse. 17 Among UCLA Phase 2 XR-NTX Participants (N=220)

18. Reduced Urge to Drink/Use by Gender Based on the Urge to Drink/Use Scale, which is scored from 0 to 30. A score of 10 or more indicates danger of relapse. 18 Among UCLA Phase 2 XR-NTX Participants (N=220)

19. Limited Side Effects 19 Among UCLA Phase 2 Participants (N=220)

20. Clinical Characteristics by Gender Side Effects Reported Total (N=220) Male (N=110) Female (N=110) Average number of side effects Week 1 2.1 (1.3)1.9 (1.4)2.2 (1.3) Week 2* 1.1 (1.2)0.9 (1.1)1.3 (1.2) Any side effects Week 1**85.579.092.0 Week 2**57.246.468.0 Headache Week 139.536.043.0 Week 2**28.919.638.1 *p<.05; **p<.01 20 Among UCLA Phase 2 XR-NTX Evaluation Participants (N=220)

21. Comparison Results Results Significant at p<.05 or better 21

22. Two Groups XR-NTX (n = 190) –Received at least one dose of medication –No random assignment – wanted medication, got medication Post-hoc Comparison (TAU) (n = 190) –Did not receive medication –Demographics matched to XR-NTX group –Calculated propensity scores

23. Participant Characteristics Categorical Variable XR-NTX Group (% yes) Post-hoc TAU Group (% yes) Test Statistic Gender (Female)55.3%56.8%X 2 = 0.096 Race/Ethnicity White African American Latino Other 41.1% 13.2% 41.1% 4.7% 43.7% 12.1% 40% 4.2% X 2 = 0.323 Criminal Justice Involvement (yes)31.6%33.2%X 2 =.108 Homeless status (yes)40.5%35.3%X 2 = 1.118 Employment Activities (yes)10%14.2%X 2 = 1.583 Program Type (Outpatient)35.3%34.7%X 2 =.012 Mental Illness* (yes)44.7%32.1%X 2 = 6.407 *Lifetime report of mental illness differed between groups; p<.01 23

24. Participant Characteristics *Days spent on the wait list significantly differed between the groups p<.001. Continuous Variable XR-NTX Group Mean (sd) Post-hoc TAU Group Mean (sd) Test Statistic Age at Admission37.2 (9.5)36.8 (10.7)t(374) = -.469 Age at First Use17.1 (6.3)17 (6.1)t(378) = -.173 Days of Primary Drug in the Last 30 8.2 (9.5)10.2 (11.3)t(378) = 1.877 # of Prior Treatment Episodes2.2 (3.7)2 (6)t(378) = -.463 Days on Wait List*7.2 (13.6)3.7 (10.5)t(378) = -2.826 Age at Admission37.2 (9.5)36.8 (10.7)t(374) = -.469 Age at First Use17.1 (6.3)17 (6.1)t(378) = -.173 24

25. Engagement & Completion Rates for XR-NTX and Post Hoc (TAU) Clients Engagement and Completion Rates of XR-NTX Treatment Clients vs. TAU Treatment Clients 25

26. XR-NTX & Engagement Engagement = In treatment for 30+ days Predictors included –XR-NTX (p <.001) OR (95% CI) = 12.609 (5.178-30.706) –Age at first use (p <.05) OR (95% CI) = 1.066 (1.009-1.126) 26

27. XR-NTX & Retention Retention = In treatment for 90+ days Predictors included –XR-NTX (p <.001) OR (95% CI) = 3.868 (2.352 – 6.361) –Race (African American vs. White) (p <.05) OR (95% CI) =.380 (.175 -.826) –Mental illness diagnosis (p <.01) OR (95% CI) = 2.415 (1.370 – 4.258) 27

28. ADDITIONAL FINDINGS 28

29. Treatment providers may have promoted XR- NTX to the patients with more severe SUD histories Men and some racial/ethnic minorities may be underrepresented among XR-NTX recipients Further research is warranted to examine if geographic area or organizational characteristics predicts access to XR-NTX Bottom Line: Not only is it important to provide evidence based practices, like MAT, but it is also important to ensure equal access for all patients. 29 Examine Access to Prevent Disparity

30. Addressing Barriers LA County increased availability of XR-NTX as a treatment option Obtained a grant for drug court patients Medication hubs linked with referring agencies to provide medical screenings and provide XR-NTX doses Transportation to/from Tx and the medication hub was coordinated Education sessions to increase knowledge of MAT among Tx providers

31. Summary of Findings on Gender No differences in the total number of doses (not shown) by gender Women may have a greater need for SUD treatment that addresses co-occurring MH and parenting needs Women may need support in managing side effects Qualitative findings (not shown) suggest similar experiences with XR-NTX 31

32. TREATMENT INTEGRATION? What about: 32

33. Expansion of Availability of MAT Number of SUD treatment programs with patients taking XR-NTX before LA County Study: 1 program Number of SUD treatment programs with patients taking XR-NTX after LA County Study: 32 programs 33

34. Expansion to Other Areas of CA? Many other counties and jurisdictions in CA using the medication: –Orange County: starts in jail, also used by probation –Santa Cruz County: similar to OC program –San Mateo County: DD clients with AUD –Sacramento: small, but very successful – no crime, tx compliant, clean urines –San Francisco: VA using with Homeless Veteran project 34

35. Use of Medication Requires Collaboration In all counties, some collaboration needed between (some or all of) offices below –Substance Use Treatment –Primary Healthcare –Sheriff’s Department –Probation Department –Behavior Health Funding varied – Medi-Cal (not Drug), AB109, Gov grants 35

36. Conclusions Although no causal conclusions can be made, XR-NTX was associated with increases in –Treatment engagement –Treatment retention –Positive compliance in treatment –Reductions in use were noted 36

37. Policy Changes Substantial work done to reduce time required to get approval from Medi-Cal –Down from almost 3 months to 3-5 days Given results from first pilot, doses are capped at 3; but client may acquire additional doses if –Request made to Medical Director at SAPC –Urges remain high –Client remains in treatment 37

38. 45-year-old, Latina female who has been trying to stop drinking for 15 years. She has been in “over 20 detoxes” and this is her fifth time in residential treatment. This is the first time, thanks to XR-NTX, that she has lost the craving for alcohol since she began drinking as an adolescent.

39. 52-year-old, Caucasian male who has been drinking since 14 years of age. He tried to stop drinking for 25 years on his own or through 12-step programs. He never achieved more than 3-4 months of sobriety at a time. This is his 2 nd Tx program; in his first program he lasted two months – “thinking about drinking every single day. I couldn’t get it out of my head, so I left.” Currently, he has received 2 XR-NTX injections and has “been able to concentrate on the counseling work” since the third day after his first injection. He was on a pass last week and passed the liquor store where he has been “keeping a tab” for 15 years and “didn’t even realize I went by it until I was three blocks away. XR-NTX is fantastic!”

40. 36-year-old, American Indian male with a 20-year history of alcohol and methamphetamine abuse and a co occurring diagnosis of bipolar disorder. He has been in treatment 4 times since he began trying to stop using 8 years ago. While he did manage to stop using meth 4 years ago, his daily drinking has been steadily getting worse over the last two years, most often leading to blackouts. He has received 4 XR-NTX injections so far and says he has not had any urges to drink since “a couple of days after the first shot.”

41. Acknowledgements Sarah J. Cousins, MPH Kira Jeter, MA Diane Herbeck, MA Eva Vasquez Reham Abdel Maksoud, MBBS Stefanie Weimann, MA Dave Bennett, BA Mary-Lynn Brecht, PhD Richard A. Rawson, PhD Loretta L. Denering, MS 41

42. Thank You! Desiree A. Crevecoeur-MacPhail, Ph.D. (310) 267-5207 email: desireec@ucla.edudesireec@ucla.edu 42