1. Treatment of Methamphetamine Dependence: Behavioral and Psychosocial Treatments Pharmacotherapy Development Richard A. Rawson, Ph.D, Professor Semel Institute for Neuroscience and Human Behavior David Geffen School of Medicine University of California at Los Angeles www.uclaisap.org rrawson@mednet.ucla.edu Supported by: National Institute on Drug Abuse (NIDA) National Institute on Drug Abuse (NIDA) Pacific Southwest Technology Transfer Center (SAMHSA) Pacific Southwest Technology Transfer Center (SAMHSA) International Network of Treatment and Rehabilitation Resource Centres (UNODC)

3. Are Treatment Outcomes for Individuals with Methamphetamine Dependence Different than for Other Drug Dependencies?

4. Meth Treatment Effectiveness? A pervasive rumor has surfaced in many geographic areas with elevated MA problems:  MA users are virtually untreatable with negligible recovery rates.  Rates from 5% to less than 1% have been quoted in newspaper articles and reported in conferences.  Representatives for some commercial treatment concerns have suggested there are no effective treatments for methamphetamine dependence.

5. Meth Treatment Statistics During the 2007-2008 fiscal year:  42,100 individuals were admitted to treatment in California under the Substance Abuse and Crime Prevention Act funding.  Of this group, 53% reported MA as their primary drug problem

6. Statistics A comparison of treatment outcomes between individuals diagnosed with methamphetamine dependence and all other diagnostic groups indicated no between group significant differences in any treatment outcome measures including:  Retention in treatment rates  Urinalysis data during treatment  Rates of treatment program completion. All these measures indicate that MA users respond in an equivalent manner as individuals admitted for other drug abuse problems.

7. Do Methamphetamine Users Respond Differently to Treatment than Cocaine Users?

8. Comparability of Treatment Outcome: Cocaine vs Methamphetamine Alice Huber, Walter Ling and Richard Rawson * Cohorts of methamphetamine dependent patients (N=500) and cocaine dependent patients (N=224) treated with a standardized, outpatient treatment protocol (Matrix Model) at the same clinic site, by the same staff over the same time period, demonstrated very similar treatment response on virtually all treatment participation and outcome measures * Jnl of Addictive Diseases, 18, 1997, P 41-50.

10. Differences between methamphetamine users and cocaine users in treatment Amy L. Copeland and James L. Sorensen* The two populations did not differ in treatment adherence, as measured by clinic attendance, drug-free urines, and successful completion of treatment. The two populations did not differ in treatment adherence, as measured by clinic attendance, drug-free urines, and successful completion of treatment. * Drug and Alcohol Dependence, Volume 62, March 2001, Pages 91-95

11. Treatment response by primary drug of abuse: Does methamphetamine make a difference? Bill Luchansky, Antoinette Krupski, and Kenneth Stark*  For both adults and youth, the results showed that across outcomes, there were few differences between MA users and users of other hard drugs, whereas there were consistent differences between MA users and users of alcohol and marijuana. Alcohol and marijuana users tended to have more positive outcomes than the other groups. * Journal of Substance Abuse Treatment Vol 32, 2007, Pages 89-96 Journal of Substance Abuse Treatment Journal of Substance Abuse Treatment

12. Summary  Treatment outcome data indicate that psychosocial treatments used in community treatment programs produce comparable outcomes for methamphetamine dependent individuals and those with other forms of drug dependency

13. Development of pharmacotherapies for treatment of substance use disorders  The development of medications for the treatment of substance use disorders has been a major endeavor by NIH over the past 20 years.  Efficacious medications for the treatment of alcohol dependence have been identified Naltrexone (Revia) Naltrexone (Revia) Naltrexone depot (Vivitrol) Naltrexone depot (Vivitrol) Acamprosate (Campral) Acamprosate (Campral) Topiramate (Topomax) Topiramate (Topomax)  Efficacious medications have been identified for opiate addiction Methadone Methadone Naltrexone Naltrexone Buprenorphine Buprenorphine

14. Development of Pharmacotherapies for Methamphetamine Dependence  A number of medications have been reported by clinicians to be useful in the treatment of methamphetamine dependence (eg. fluoxitine, sertraline, imipramine, ondansetron, flupenthixol, tryptophan, etc.). All have been found to be no more efficacious than placebo when tested in double-blind placebo controlled trials.  Only buproion has any evidence of efficacy for the treatment of methamphetamine (and only with less severe users). Elkashef, et al. (2007) Neuropharmacology.

15. Summary: Pharmacotherapy Development  A number of medications have been established as efficacious for the treatment of alcohol and opiate dependence disorders.  The evaluation of new medications and new medical procedures requires and extensive program of safety and efficacy testing before a treatment is recognized by the FDA as approved for use by the public.  At a US House Committee hearing, when asked if she supported use of untested treatments for addictions Nora Volkow, MD Director of NIDA, said “…it has become extraordinarily important for us to provide objective evidence of the effectiveness of treatment interventions…. …. Do I support the utilization of treatments that are not evidence-based? No, I do not.” (June 28, 2006)

16. Which behavioral and psychosocial treatments have demonstrated efficacy for stimulant dependence treatment?

17. Characteristics of studies used to establish treatment efficacy  Studies which have established the efficacy of behavioral and psychosocial treatments have: Treatment group and comparison group(s) Treatment group and comparison group(s) Random assignment of participants to groups Random assignment of participants to groups Drug use as measured by urinalysis used as the essential primary dependent measure Drug use as measured by urinalysis used as the essential primary dependent measure Independent research staff collects and analyzes data Independent research staff collects and analyzes data Efficacy is evaluated during treatment and/or at treatment end and at post treatment follow up Efficacy is evaluated during treatment and/or at treatment end and at post treatment follow up

18. Treatments for Stimulant-use Disorders with Empirical Support  Cognitive-Behavioral Therapy (CBT)  Community Reinforcement Approach  Contingency Management  12 Step Facilitation All have empirical support for the treatment of cocaine dependence

19. Methamphetamine Treatment: Controlled Clinical Trials Cognitive Behavioral Therapy Contingency Management Matrix Model

20. Cognitive Behavioral Therapy and Contingency Management for Stimulant Dependence  Design Randomized clinical trial.  Participants Stimulant-dependent individuals (n = 171).  Intervention CM, CBT, or combined CM and CBT, 16-week treatment conditions. CM condition participants received vouchers for stimulant-free urine samples. CBT condition participants attended three 90-minute group sessions each week. CM procedures produced better retention and lower rates of stimulant use during the study period.  Results Stimulant use was reduced from baseline levels to follow-up for all groups and urinalysis data did not differ between groups at follow-up. CM produced evidence of efficacy during treatment, CBT produced comparable longer-term outcomes. There was no evidence of an additive effect when the two treatments were combined. The response of cocaine and methamphetamine users was comparable.  Conclusions: This study suggests that CM is an efficacious treatment for reducing stimulant use and is superior during treatment to a CBT approach. CM is useful in engaging substance abusers, retaining them in treatment, and helping them achieve abstinence from stimulant use. CBT also reduces drug use from baseline levels and produces comparable outcomes to CM on all measures at follow-up.  Rawson, RA et al. Addiction, Jan 2006

21. CBT: Basic Assumptions  Emphasizes cognitive aspects of drug/alcohol use as learned behavior Role of cognitions in abstinence Role of cognitions in abstinence  “Treatment” is a teaching process, coaching and reinforcing; “therapist” is a teacher/coach  No assumption of underlying psychopathology  New, alternative behaviors must be established  Can be delivered in group or individual settings

22. Contingency Management  A technique employing the systematic delivery of positive reinforcement for desired behaviors. In the treatment of methamphetamine dependence, vouchers or prizes can be “earned” for submission of methamphetamine-free urine samples.

23. FIGURE 2. Stimulant–free Urine Samples by Group

24. FIGURE 4. Stimulant-free Samples as a Percentage of Samples Collected at Follow-up

25. Contingency Management: An Evidence-Based Component of Methamphetamine Use Disorder Treatments* *Roll, J. Contingency management: an evidence based component of methamphetamine use disorder treatments. Addiction. 2007;102 (Suppl. 1):114-120.

26. Contingency Management for Treatment of Methamphetamine Dependence  Design: RTC  Method: 113 patients diagnosed with methamphetamine abuse or dependence were randomly assigned to receive either treatment as usual (TAU) or TAU plus contingency management.  Results indicate that both groups were retained in treatment for equivalent times but those in the CM group accrued more abstinence and were abstinent for a longer period of time. These results suggest that contingency management is an efficacious component in methamphetamine treatment strategies. * Roll JM, Petry NM, Stitzer ML, et al: Contingency management for the treatment of methamphetamine use disorders. Am J Psychiatry 163(11):1993-1999, 2006

29. Contingency Management Treatment Studies CM study involving gay and bisexual men [Shoptaw et al. (2005)] CM study involving gay and bisexual men [Shoptaw et al. (2005)] CBT, CM, CM+CBT, or CBT designed for gay and bisexual men (GCBT)CBT, CM, CM+CBT, or CBT designed for gay and bisexual men (GCBT) Participants in CM conditions stayed in treatment longer and had longer periods of continuous abstinenceParticipants in CM conditions stayed in treatment longer and had longer periods of continuous abstinence Another study examined the effectiveness of CM + CBT and sertraline for MA addiction [Shoptaw et al. (2006)] Another study examined the effectiveness of CM + CBT and sertraline for MA addiction [Shoptaw et al. (2006)] Those in the CM conditions were more likely to attain a 3-wk period of in-treatment abstinenceThose in the CM conditions were more likely to attain a 3-wk period of in-treatment abstinence

30. Matrix Model in Treatment of Methamphetamine Dependence  Design: The study was conducted as an eight-site randomized clinical trial.  Method: 978 treatment-seeking, MA-dependent persons were randomly assigned to receive either TAU at each site, or a manualized 16-week treatment (Matrix Model) for their MA dependence.  Results: Analyses of study data indicate that in the overall sample, and in the majority of sites, those who were assigned to Matrix treatment attended more clinical sessions, stayed in treatment longer, provided more MA-free urine samples during the treatment period, and had longer periods of MA abstinence than those assigned to receive TAU. Measures of drug use and functioning collected at treatment discharge and 6 months post-admission indicate significant improvement by participants in all sites and conditions when compared to baseline levels, but the superiority of the Matrix approach did not persist at these two time points.  Conclusions: Study results demonstrate a significant initial step in documenting the efficacy of the Matrix approach. The in-treatment benefit of the Matrix approach is a demonstration of the efficacy of this psychosocial treatment approach.  Rawson, R et al Addiction vol 99, 2004

31. Matrix Model  Is a manualized, 16-week, non-residential, psychosocial approach used for the treatment of drug dependence.  Manuals Can be downloaded at SAMHSA.gov  Designed to integrate several interventions into a comprehensive approach. Elements include: Individual counseling Individual counseling Cognitive behavioral therapy Cognitive behavioral therapy Motivational interviewing Motivational interviewing Positive reinforcement for behavior change Positive reinforcement for behavior change Family education groups Family education groups Urine testing Urine testing Participation in 12-step programs Participation in 12-step programs

32. Rawson, R.A., Marinelli-Casey, P., Anglin, M.D., Dickow, A., Frazier, Y., Gallagher, C., Galloway, G.P., Herrell, J., Huber, A., McCann, M.J., Obert, J., Pennell, S., Reiber, C., Vandersloot, D., Zweben, J., and the Methamphetamine Treatment Project Corporate Authors. (2004). A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence. Addiction, 99, 708-717. The CSAT Methamphetamine Treatment Project A Multi-site Trial of a Manualized Psychosocial Protocol for the Treatment of Methamphetamine Dependence

33. Mean Number of Weeks in Treatment

34. Mean Number of UA’s that were MA-free during treatment

35. Urinalysis Results  Results of Ua Tests at Discharge, 6 months and 12 Months post admission ** Matrix GroupTAU GroupMatrix GroupTAU Group D/C: 66% MA-free 65% MA-free 6 Ms: 69% MA-free 67% MA-free 12 Ms: 59% MA-free 55% MA-free **Over 80% follow up rate in both groups at all points

36. 3-Year Follow-Up Study

37. Participants  All previous 1016 MTP participants were eligible for participation  The 3-year Follow-Up Study was conceptualized during the middle of MTP data collection  Those who provided permission to be contacted for future studies or those that contacted the study team could participate (n = 672)  A total of 587 interviews were completed: 41 participants were not found; 3 had died, 34 were unable to participate (incarcerated, moved out of the country, unable to schedule), and 7 refused to participate

38. Route of Administration (MTP Baseline)

39. Patterns of Methamphetamine Use Is the status and functioning of participants at the 3-year follow-up related to the severity of MA use since discharge from MTP?

40. Participants divided into 4 groups (use in follow-up period)*: (1) No MA use (MA-free, 23.5%) (2) Minimal MA use (MA use 1-10 months, 26.4%) (3) Moderate MA use (MA use 11-25 months, 25.2%) (4) Heavy MA use (MA use 26+ months, 25.0%) *MA Use was measured as any use (yes/no) in each month of the follow- up period – no distinction by amount or frequency of use during each month of use.

41. Findings  Those who reported no use over the follow- up period generally had better ASI composite scores (all but medical, alcohol use), lower rates of other drug use, lower depression scores, and lower rates of criminal activities than other groups.  Those with heaviest use over the follow-up period generally had worse scores indicating more problems.

42. Drug Courts and Methamphetamine Users  An examination was conducted of the urinalysis data from 2 California drug court programs using behavioral treatments including the Matrix Model found excellent treatment response as evidenced by urinalysis data. In one program treating 760 meth users in Rancho Cucamonga Calif, over a 6 year period and over 40,000 urine samples, the rate of drug free samples was 96.5% In one program treating 760 meth users in Rancho Cucamonga Calif, over a 6 year period and over 40,000 urine samples, the rate of drug free samples was 96.5% In a second drug court program in Hayward, California, over a 2 year period with 130 meth dependent clients patients, the rate of drug free urine samples was 97.2%. In a second drug court program in Hayward, California, over a 2 year period with 130 meth dependent clients patients, the rate of drug free urine samples was 97.2%.

43. Drug court treatment for methamphetamine dependence: Treatment response and post-treatment outcomes, Marinelli- Casey, Gonzales, Hillhouse, Ang, Zweben, Cohen, Hora and Rawson JSAT, 34, 242-248, 2008  A group of 57 MA-dependent participants treated in outpatient treatment within the context of a drug court were compared to a group of comparable MA-dependent individuals treated in outpatient treatment but not supervised by a drug court (n = 230).  Drug court participation was associated with better rates of engagement, retention, completion, and abstinence, compared to outpatient treatment without drug court supervision.  Six- and 12-month outcome analyses indicated that participants who were enrolled in drug court intervention used MA significantly less frequently.  These findings suggest that drug court supervision coupled with treatment may improve the outcomes of MA-dependent offenders beyond that seen from treatment alone.

44. Change in MA Use Overtime Among Drug Court &. Non-Drug Court Participants

45. Clinical Strategies to Enhance Treatment Outcomes with Methamphetamine Users  Educate clients about the reality of MA addiction including: biology impacted by MA; biology impacted by MA; conditioning factors that create craving; conditioning factors that create craving; common relapse scenarios (eg. drug using friends, alcohol, extended periods of unstructured time); common relapse scenarios (eg. drug using friends, alcohol, extended periods of unstructured time); how MA impacts families; how MA impacts families; potential benefits of mental health care; potential benefits of mental health care; relationship between participation in aftercare/community care and relapse/recidivism. relationship between participation in aftercare/community care and relapse/recidivism.

46. Clinical Strategies to Enhance Treatment Outcomes with Methamphetamine Users  Employ varied adult learning formats to increase comprehension and retention of knowledge in view of cognitive deficiencies (especially verbal memory problems).  Incorporate presentations by recovering MA users to reinforce treatment messages.  Provide “workbooks” and learning aids on relapse prevention for clients to take with them into continuing care.

47. Clinical Strategies to Enhance Treatment Outcomes with Methamphetamine Users  Strategies to reduce anhedonia and negative mood states, episodic paranoia, sleep problems (aerobic exercise, Yoga, Tai Chi, meditation)  Anger management strategies (to cope with possible serotonergic dysregulation-induced irritability).  Groups to address extensive maladaptive sexual behaviors and expectations.  Whenever possible, educate family members about ways they can promote recovery.

48. Clinical Strategies to Enhance Treatment Outcomes with Methamphetamine Users  During pre-release period (30 days?) emphasize relapse prevention tools, including time planning, identifying triggers and high risk situations, practice craving prevention/reduction strategies and behavioral strategies for saying “no”.  To the extent possible make residential treatment and community aftercare as congruent and complimentary as possible. Coordinate treatment content, language, philosophy and recovery “message” between residential care and community aftercare.

49. Clinical Strategies to Enhance Treatment Outcomes with Methamphetamine Users  The single most important factor for positive treatment outcome will be the degree to which clients are retained in post-residential treatment. Use community care organizations with a continuum of care that can decrease and increase intensity of care when clinically indicated. Use community care organizations with a continuum of care that can decrease and increase intensity of care when clinically indicated. Create treatment plans that maximize compliance Create treatment plans that maximize compliance Employ positive reinforcement (vouchers-contingency management) methods to promote retention and prosocial alternative behaviors. Employ positive reinforcement (vouchers-contingency management) methods to promote retention and prosocial alternative behaviors. Coordinate parole monitoring and treatment participation in community care. Coordinate parole monitoring and treatment participation in community care. Make mental health care available. Make mental health care available. Involve family in community care services. Involve family in community care services.

50. Early Recovery Groups  Scheduling and Calendars  Triggers  Questionnaires and Chart  12 Step Introduction  Alcohol Issues  Thoughts Emotions and Behaviors  KISS (and other 12-step slogans)

51. Early Recovery Issues Engaging and Retaining TRIGGERS

52. Early Recovery Issues Engaging and Retaining TriggerThoughtCravingUse

53. Trigger Thought Craving Use Early Recovery Issues Engaging and Retaining

54. Triggers - Places Triggers - Places Drug dealer’s home Bars and clubs Drug use neighborhoods Freeway offramps Worksite Street corners

55. Triggers - Things Triggers - Things Paraphernalia Sexually explicit magazines/movies Money/bank machines Music Movies/TV shows about alcohol and other drugs Secondary alcohol or other drug use

56. Triggers - Times Triggers - Times Periods of idle time Periods of extended stress After work Payday/AFDC payment day Holidays Friday/Saturday night Birthdays/Anniversaries

57. Triggers - Emotional States Triggers - Emotional States  Anxiety  Fatigue  Anger  Boredom  Frustration  Adrenalized states  Sexual arousal  Sexual deprivation  Gradually building emotional states with no expected relief

58. THOUGHT STOPPING Prevents the thought from developing into an overpowering craving Requires practice TriggerThought Thought Stopping Continued ThoughtsUseCravings

59. MOTIVATIONAL INTERVIEWING  Increase Motivation  Decrease Resistance  Increase retention  Better outcomes

60. INFORMATION

61. Information - What Information - What - Substance abuse- Sex and recovery and the brain- Relapse prevention issues - Triggers and cravings- Emotional readjustment - Stages of recovery- Medical effects - Relationships and recovery - Alcohol/marijuana

62. Information - Why Information - Why Reduces confusion and guilt Explains addict behavior Gives a roadmap for recovery Clarifies alcohol/marijuana issue Aids acceptance of addiction Gives hope/realistic perspective for family

63. Matrix Relapse Prevention Groups

64. Relapse Prevention Group Topics (Sample)  Alcohol -The Legal Drug  Boredom  Avoiding Relapse Drift/Mooring Lines  Guilt and Shame  Motivation for Recovery  Truthfulness  Work and Recovery  Staying Busy  Relapse Prevention  Dealing with Feelings

65. Acute vs Chronic Treatment

66. An Acute Model of Treatment vs Chronic Model of Treatment

67. An Acute Care Treatment Model Treatment Substance Abusing Patient Non- Substance Abusing Patient

68. A Chronic Care Model Detox Substance Abusing Patient Continuing Care Recovering Patient Rehab Duration Determined by Performance Criteria Duration Determined by Performance Criteria

69. A Chronic Care Model Detox Continuing Care Recovering Patient Rehab Duration Determined by Performance Criteria Duration Determined by Performance Criteria

70. Types of Continuing Care  Self/mutual help programs  Medications  Traditional counseling visits  Home visits  Recovery “check-ups” Specialty care-based Specialty care-based Primary care-based Primary care-based  Telephone-based protocols Monitoring Monitoring Monitoring and counseling Monitoring and counseling  Other stuff

71. Recovery Management Checkups  Protocol developed by Dennis, Scott et al. Interview patients every quarter for 2 years Interview patients every quarter for 2 years If patient reports any of the following…… If patient reports any of the following…… Use of alcohol or drugs on > 2 weeksUse of alcohol or drugs on > 2 weeks Being drunk or high all day on any daysBeing drunk or high all day on any days Alcohol/drug use led to not meeting responsibilitiesAlcohol/drug use led to not meeting responsibilities Alcohol/drug use caused other problemsAlcohol/drug use caused other problems Withdrawal symptomsWithdrawal symptoms …Patient transferred to linkage manager …Patient transferred to linkage manager

72. Recovery Management Checkups  Linkage Manager provides the following: Personalized feedback Personalized feedback Explore possibility of returning to treatment Explore possibility of returning to treatment Address barriers to returning to treatment Address barriers to returning to treatment Schedule an intake assessment Schedule an intake assessment Reminder cards, transportation, and escort to intake appointment Reminder cards, transportation, and escort to intake appointment

73. Telephone as a continuing care tool  Potential to promote better long-term engagement and participation because: Convenient for client Convenient for client Reduces stigma of weekly trips to the treatment program Reduces stigma of weekly trips to the treatment program Individualized attention Individualized attention Can be automated (Helzer, Searles et al.) Can be automated (Helzer, Searles et al.) Lower costs of ongoing care (?) Lower costs of ongoing care (?)

74. Measuring Program Performance: A Key to a Successful Continuum of Care Program Performance: What is it and how will we measure it?

75. Summary: Behavioral and Psychosocial Treatments for Stimulant Dependence  There are effective treatments for methamphetamine dependence.  Treatments with evidence of efficacy for cocaine dependence appear efficacious for the treatment of methamphetamine dependence.  Methamphetamine dependence treatments with evidence of efficacy in randomized controlled clinical trials include: Cognitive behavioral therapy Cognitive behavioral therapy Contingency management Contingency management Motivational interviewing Motivational interviewing Matrix model Matrix model

76. Thank you rrawson@mednet.ucla.edu www.uclaisap.org www.methamphetamine.org rrawson@mednet.ucla.edu www.uclaisap.org rrawson@mednet.ucla.edu www.uclaisap.org