1. Richard Rawson Ph.D. U.C.L.A. Integrated Substance Abuse Programs (I.S.A.P.) The MTP Site Investigators Funded by the Center for Substance Abuse Treatment The CSAT Methamphetamine Treatment Project A Multi-site Trial of a Manualized Psychosocial Protocol for the Treatment of Methamphetamine Dependence

2. Powerfully addictive stimulant thatdramatically affects the central nervous system Made easily in clandestine labs with OTC ingredients What Is Methamphetamine?

3. Methamphetamine comes in many forms and can be: Smoked Snorted Orally Ingested Injected How Is Methamphetamine Taken?

4. Scope of the Methamphetamine Problem Worldwide According to surveys and estimates by WHO and UNDCP, methamphetamine is the most widely used illicit drug in the world except for cannabis. World wide it is estimated there are over 35 million regular users of methamphetamine, as compared to approximately 15 million heroin users and 10 million cocaine users

5. Scope of Methamphetamine Use in the United States Methamphetamine abuse, long reported as the dominant drug problem in Honolulu, Hawaii and San Diego, CA, has become a substantial drug problem in other sections of the West, Midwest & Southwest, as well. Indications that it is spreading to rural and urban sections of the South and East coast. Once traditionally associated with white, male, blue-collar workers. Now is being used by more diverse population groups that change over time and differ by geographic area.

6. Groups with High Rates of Meth Use Women Residents in Western/Midwestern Rural Areas and Small/Medium Cities Predominantly Caucasian, Increasing Numbers of Hispanics Gay Men

7. CSAT MTP Project Goals: To study the clinical effectiveness of the Matrix Model To compare the effectiveness of the Matrix model to other locally available outpatient treatments To establish the cost and cost effectiveness of the Matrix model compared to other outpatient treatments To explore the replicability of the Matrix model and challenges involved in technology transfer

8. Manuals in Psychosocial Treatment Reduce therapist differences Ensure uniform set of services Can more easily be evaluated Enhance training capabilities Facilitate research to practice

9. Matrix Model of Outpatient Treatment Organizing Principles of Matrix Treatment  Program components based upon scientific literature on promotion of behavior change.  Program elements and schedule selected based on empirical support in literature and application.  Program focus is on current behavior change in the present and not underlying “causes” or presumed “psychopathology”.  Matrix “treatment” is a process of “coaching”, educating, supporting and reinforcing positive behavior change.

10. Matrix Model of Outpatient Treatment Organizing Principles of Matrix Treatment  Non-judgemental, non-confrontational relationship between therapist and patient creates positive bond which promotes program participation.  Therapist as a “coach”  Positive reinforcement used extensively to promote treatment engagement and retention.  Verbal praise, group support and encouragement other incentives and reinforcers.

11. Matrix Model of Outpatient Treatment Organizing Principles of Matrix Treatment  Accurate, understandable, scientific information used to educate patient and family members  Effects of drugs and alcohol  Addiction as a “brain disease”  Critical issues in “recovering” from addiction

12. Matrix Model of Outpatient Treatment Organizing Principles of Matrix Treatment  Behavioral strategies used to promote cessation of drug use and behavior change  Scheduling time to create “structure”  Educating and reinforcing abstinence from all drugs and alcohol  Promoting and reinforcing participation in non- drug-related activities

13. Matrix Model of Outpatient Treatment Organizing Principles of Matrix Treatment  Cognitive-Behavioral strategies used to promote cessation of drug use and prevention of relapse.  Teaching the avoidance of “high risk” situations  Educating about “triggers” and “craving”  Training in “thought stopping” technique  Teaching about the “abstinence violation effect”  Reinforcing application of principles with verbal praise by therapist and peers

14. Matrix Model of Outpatient Treatment Organizing Principles of Matrix Treatment  Involvement of family members to support recovery.  Encourage participation in self-help meetings  Urine testing to monitor drug use and reinforce abstinence  Social support activities to maintain abstinence

15. Matrix Model An Integrated, Empirically-based, Manualized Treatment Program

16. Elements of the Matrix Model Engagement/Retention Structure Information Relapse Prevention Family Involvement Self Help Involvement Urinalysis/Breath Testing

17. The Matrix Model MondayWednesdayFriday Early Recovery Skills Weeks1-4 Family/education Weeks 1-12 Early Recovery Skills Weeks1-4 Relapse Prevention Weeks 1-16 Social Support Weeks 13-16 Relapse Prevention Weeks 1-16  Urine or breath alcohol tests once per week, weeks 1-16

18. Table 1. Sites participating in the MTP (from Herrell et al, 2000) Coordinating CenterPrincipal Investigators Directors University of California at Los Angeles (UCLA) Integrated Substance Abuse Programs (ISAP) M. Douglas Anglin, Ph.D. Richard A. Rawson, Ph.D. Patricia Marinelli-Casey, Ph.D., Project Director Jeanne Obert, MFT, Clinical Alice Huber, Ph.D. Research Chris Reiber, Ph.D. Statistics Grantee / Site*Principal InvestigatorLead Evaluator County of San Mateo, Belmont, CA: Two sites: ODASA and Pyramid Yvonne Frazier, Ph.D. County of San Mateo, Alcohol and Drug Services; Belmont, CA Joseph Guydish, Ph.D. University of California at San Francisco; San Francisco, CA East Bay Community Recovery Project, Hayward, CA Joan Zweben, Ph.D. East Bay Community Recovery Project; Hayward, CA Judith Cohen, Ph.D., M.P.H. East Bay Community Recovery Project; Hayward, CA Matrix Institute, Costa Mesa, CA Michael McCann, M.A. Matrix Institute; Costa Mesa, CA Vikas Gulati, B.S. Matrix Institute; Costa Mesa, CA New Leaf Treatment Center, Lafayette, CA Gantt Galloway, Pharm.D. New Leaf Treatment Center; Lafayette, CA Janice Stalcup, Ph.D. New Leaf Treatment Center; Lafayette, CA San Diego Association of Governments, San Diego, CA Susan Pennell, M.A. San Diego Association of Governments; San Diego, CA Cynthia Burke, Ph.D. San Diego Association of Governments; San Diego, CA South Central Regional Mental Health Center, Billings, MT Denna Vandersloot, B.S. South Central Regional Mental Health Center; Billings, MT Russell H. Lord, Ph.D. Montana State University; Billings, MT St. Francis Medical Center, Honolulu, HI A lice Dickow, B.A. St. Francis Women’s Addiction Treatment Center, Hawaii; Honolulu, HI Ewa Stamper, Ph.D. St. Francis Women’s Addiction Treatment Center, Hawaii; Honolulu, HI

19. Site Duration of Treatment Intensive Phase Individual Sessions Group Sessions 12-Step Program Involvement Site 1 8 wks 1x/wk x 4-8 wks, 30-50 min each 4x/wk x 4-8 wks, 3hr each, families attend 1x/wk required; 1x/wk x 4-8 wks Site 2 12 wks 1x/wk x 12 wks, 1 hr each 5x/wk x 2wk, 3x/wk x 2wks, 2x/wk x 8 wks recommended Site 3 12 wks 1x/wk x 12 wks, 1 hr each nonerecommended Site 4 16 wks 1x/wk x 16 wks, 10-15 min each 3x/wk x 16 wks, 1 hr each required; 3x/wk x 16 wks Site 5 12 wks 1x/wk x 12 wks, 30-60 min each 3x/wk x 12 wks, 90 min each and 2x/wk x 12 wks, 60- 90 min each required; 1x/wk x 12 wks Site 6 12 wks 1x/wk – 2x/mo x 12 wks, 1 hr each 2x/wk x 12 wks, 90 min each, families attend 1x/2 wks recommended Site 7 16 wks 1x/wk x 16 wks, 1 hr each 2x/wk x 16 wks, 2 hrs each recommended Site 8 12 wks 2x/wk x 12 wks, 1 hr each 1x/wk x 12 wks, 2 hrs each required; 6 meetings Table 2. Treatment-As-Usual: Elements of Treatment

20. Site TAU (n) Matrix 16-week (n) Total Site 1 69 73 142 Site 27877155 Site 37776153 Site 45057107 Site 56163124 Site 67370143 Site 7242246 Site 854 108 Overall TOTAL486492978 Table 3. Enrollment in the MTP by Site and Treatment Condition

21. CharacteristicSummary % Male45 Age (Yrs.), mean (sd)32.8 (8.0) Ethnicity (%) Caucasian60 African-American2 American Indian3 Asian/Pacific Islander17 Hispanic18 Educational Attainment Level (yrs.), mean (sd)12.2 (1.7) % Employed69 % Married (and not separated)16 Overall Substance Use Patterns-Lifetime (yrs.), mean (sd) Methamphetamine7.54 (6) Alcohol7.6 (8.5) Cocaine1.75 (3.5) Cannabis7.15 (8) Overall Substance Use Patterns—Days in Past 30, mean (sd) Methamphetamine11.53 (9.6) Alcohol4.72 (7.3) Cocaine0.21 (1) Cannabis4.38 (8.3) Preferred Route of Administration of MA (%) Oral0 Nasal11 Smoked65 IV- injection24 Table 4. MTP Participant Characteristics (taken from baseline ASI)

22. Sample Description

23. Baseline Demographics Participants Served (n)1016 Age (mean)32.8 years Education (mean)12.2 years Methamphetamine Use (mean)7.5 years Marijuana Use (mean)7.2 years Alcohol Use (mean)7.6 years

24. Gender Distribution of Participants

25. Ethnic Identification of Participants

26. Marital Status of Participants

27. Employment Status of Participants

28. Route of Methamphetamine Administration

29. Changes from Baseline to Treatment-end

30. Days Paid for Work in Past 30 Possible is 0-30; t paired =6.01; p-value<0.000 (highly sig.)

31. Total Income (Past 30 days) of Participants t paired =2.34; p-value=0.02 (sig.)

32. ASI Composite Scores Possible is 0-1; Higher : worse problem t paired : *p-value<0.03 (sig.), **p-value<0.000 (highly sig.)

33. Days of Methamphetamine Use in Past 30 (ASI) Possible is 0-30; t paired =20.90; p-value<0.000 (highly sig.)

34. Days of Marijuana Use in Past 30 (ASI) Possible is 0-30; t paired =8.02; p-value<0.000 (highly sig.)

35. Days of Alcohol Use in Past 30 (ASI) Possible is 0-30; t paired =6.47; p-value<0.000 (highly sig.)

36. Beck Depression Inventory (BDI) Total Scores Possible is 0-63; t paired =16.87; p-value<0.000 (highly sig.)

37. BSI Scores (mean) BL 1 Tx-end Paired t * Somatization0.70.57.67 Obsessive-Compulsive1.20.911.40 Interpersonal Sensitivity1.00.711.40 Depression1.20.811.98 Anxiety0.90.611.24 Hostility0.80.69.39 Phobic Anxiety0.60.48.47 Paranoid Ideation1.10.711.49 Psychoticism0.90.610.70 1 Possible, all scores, is 0-4; * all p-values<0.000 (highly sig.)

38. Positive Symptom Total (PST) from Brief Symptom Inventory (BSI) Possible is 0-53; t paired =14.33; p-value<0.000 (highly sig.)

39. Site (TAU length, wks.) TAU Mean SD Matrix 16-week Mean SD Site 1 (8) 17.225.2 Site 2 (12) 21.726.1 Site 3 (12) 6.328.4 Site 4 (16) 22.831.5 Site 5 (12) 15.425.7 Site 6 (12) 2.125.2 Site 7 (16) 13.835.4 Site 8 (12) 3.922.2 Overall summary 12.726.8 Table 5. Summary of the number of clinical contacts made by participants, by treatment group and site

40. Figure 3. Participant retention throughout treatment, by site and treatment group

41. Site TAU length (wks.) Log-rank Chi-square p Site 1 8 -20.07 33.17 <0.0001 Site 212 -9.49 4.980.026 Site 312 -8.39 3.680.055 Site 416 1.64 0.260.610 Site 512 -22.30 28.74<0.0001 Site 612 -17.46 17.87<0.0001 Site 716 -5.01 3.340.067 Site 812 -10.59 7.990.005 Table 7. Comparison of retention between groups within sites, with Matrix truncated to the length of TAU at each site

42. Figure 4. Percent completing treatment, by group

43. Figure 5. Mean number of MA-free urine samples, by treatment length and treatment group (Matrix group data truncated to the length of TAU)

44. Site (TAU length, wks.) Raw DataTruncated Data Matrix16TAUMatrix16TAU tp meanSDmeanSDmeanSDmeanSD Site 1 (8) 6.233.38 3.753.38 -0.760.45 Site 2 (12) 6.254.19 4.864.19 -0.940.35 Site 3 (12) 5.753.62 4.613.62 -1.520.13 Site 4 (16) 8.448.6 8.448.6 0.130.89 Site 5 (12) 5.191.72 4.301.72 -3.700.0003 Site 6 (12) 4.243.27 3.33.27 -0.040.97 Site 7 (16) 7.04.54 7.04.54 -1.500.14 Site 8 (12) 5.393.30 4.283.30 -1.230.22 Table 8. Summary of the number of MA-free urine samples provided by participants, by treatment group and site

45. Site (TAU length, wks.) Raw DataTruncated Data Matrix16TAUMatrix16TAU tp meanSDmeanSDmeanSDmeanSD Site 1 (8) 3.5752.7542.8772.754 - 0.9820.328 Site 2 (12) 3.7532.4743.3772.474-1.470.144 Site 3 (12) 3.1971.8053.0131.805-2.160.033 Site 4 (16) 6.1405.5606.1405.560 - 0.5460.586 Site 5 (12) 3.8891.2793.4291.279 - 3.3930.001 Site 6 (12) 2.4292.3422.3142.3420.20.841 Site 7 (16) 4.6822.5424.6822.542 - 1.5860.121 Site 8 (12) 2.8332.1302.5192.130 - 0.5510.583 Table 9. Longest MA abstinent period by treatment group and site

46. Figure 2. Mean number of weekly data visits attended, by treatment length and treatment group (Matrix group data truncated to the length of TAU)

47. Discharge UA Result by Attendance During Treatment and Group Matrix 16TAU cleanmissingdirty

48. Figure 1. Overall participant follow-up by treatment condition and time point

49. 6-mos. F.U. UA Result by Attendance During Treatment and Group Matrix 16 TAU MA-missingMA+

50. Figure 5. Urinalysis Results: %Meth Negative

51. Figure 6. Participant self-report of MA use (number of days during the past 30) at enrollment, discharge, and 6-month follow-up, by treatment condition

52. MTP Study Conclusions A multisite evaluation of a research-based intervention can be conducted in community sites during a 3 year period. Six research-naïve sites and 2 experienced sites successfully were trained and conducted all necessary research activities for a complex clinical trial. A complex psychosocial treatment protocol was successfully replicated at 8 sites over a 3 year period. Over 1000 MA-Users received free treatment.

53. MTP Study Conclusions Treatment for MA dependence associated with improvements in many domains including drug use, mj use, mood, Income Matrix treatment results in longer retention, more sessions attended, more treatment completers, more MA-negative Uas, longer periods of MA abstinence * Except for drug court site

54. MTP Study Conclusions Outcomes at discharge and follow-up demonstrated comparable results between Matrix and TAU Program compliance associated with superior urinalysis results at discharge and follow-up

55. MTP Study Conclusions The design of multi-site studies has to carefully consider priorities among the following issues: – Priority of testing the null hypothesis of the primary study outcomes – Flexibility to accommodate all investigators individual site priorities and site program variability