1. Treatments for Methamphetamine- Related Disorders Richard. A. Rawson, Ph.D. UCLA Integrated Substance Abuse Programs Los Angeles California rrawson@mednet.ucla.edu www.uclaisap.org Supported by National Institute on Drug Abuse and the ATTC: Pacific Southwest Technology Transfer Center ATTC: Pacific Southwest Technology Transfer Center

2. MA Treatment Issues Acute MA Overdose Acute MA Psychosis MA “Withdrawal” Initiating MA Abstinence MA Relapse Prevention Protracted Cognitive Impairment and Symptoms of Paranoia

3. Acute MA Psychosis Extreme Paranoid Ideation Well Formed Delusions Hypersensitivity to Environmental Stimuli Stereotyped Behavior “Tweaking” Panic, Extreme Fearfulness High Potential for Violence

4. Treatment of MA Psychosis Typical ER Protocol for MA Psychosis: – Haloperidol - 5mg – Or, atypical antipsychotic (eg. respiridone) – Clonazepam - 1 mg – Cogentin - 1 mg – Quiet, Dimly Lit Room – Restraints

5. MA “Withdrawal” - Depression- Paranoia - Fatigue- Cognitive Impairment - Anxiety- Agitation - Anergia- Confusion Duration: 2 Days - 2 Weeks

6. Treatment of MA “Withdrawal” Hospitalization/Residential Supervision if: – Danger to Self or Others, or, so Cognitively Impaired as to be Incapable of Safely Traveling to and from Clinic – Otherwise Intensive Outpatient Treatment

7. Initiating MA Abstinence Key Clinical Issues: – Depression – Cognitive Impairment – Continuing Paranoia – Anhedonia – Behavioral/Functional Impairment – Hypersexuality – Conditioned Cues – Irritability/Violence

8. Treatment of MA Disorders Traditional Treatments: – Therapeutic Community – Minnesota Model – Outpatient Counseling – Psychotherapy

9. Is Treatment for Methamphetamine Effective? A major demand that competes for scarce community resources are for the treatment needs of those who have become addicted to methamphetamine (MA).

10. 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. 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. Rates from 5% to less than 1% have been quoted in newspaper articles and reported in conferences. **The resulting conclusion is that spending money on treating MA users is futile and wasteful, BUT no data exists that supports these statistics**

11. Meth Treatment Statistics During the 2002-2003 fiscal year: 35,947 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

12. Statistics Analysis of: Drop out rates Retention in treatment rates Re-incarceration rates Other measures of outcome All these measures indicate that MA users respond in an equivalent manner as individuals admitted for other drug abuse problems.

13. Data Parameters LACPRS admission and discharge data for 16 months –July 2003 – October 2004 Only Outpatient Counseling –Cocaine (N = 5,046) –Methamphetamine (N = 5,278)

14. Population Demographics CocaineDemographics –68.6% Male –31.4% Female –Age: M = 39.4, SD = 9.6 (range 18-78 yrs) Proposition 36: 42.8% Mental Illness: 13% Homeless: 10.9% MethamphetamineDemographics –64.6% Male –35.4% Female –Age: M = 32.3, SD = 8.9 (range 18-65 yrs) Proposition 36: 53% Mental Illness: 7.8% Homeless: 5.7%

15. Racial Demographics by Primary Drug

16. Route of Administration

17. Secondary Drug Use by Primary Drug

18. Length of Stay (LOS) Cocaine Mean LOS = 137.5 days Range = 0 – 835 Median = 84 Mode = 0 Less than 14 Days = 12% Less than 30 days = 9.8% Methamphetamine Mean LOS = 132.7 days Range = 0 – 870 Median = 79 Mode = 0 Less than 14 Days = 10.1% Less than 30 days = 13.6%

19. Additional Information on Population

20. Mean Days of Primary Drug Use in Last 30 Days

21. Why the “MA treatment doesn’t work” perceptions? Many of the geographic regions impacted by MA do not have extensive treatment systems for severe drug dependence. Medical and psychiatric aspects of MA dependence exceeds program capabilities. High rate of use by women, their treatment needs and the needs of their children can be daunting. Although some traditional elements may be appropriate, many staff report feeling unprepared to address many of the clinical challenges presented by these patients

22. Clinical Challenges of MA Users Clinical Challenges of MA Users Poor treatment engagement rates High drop out rates Severe paranoia High relapse rates Ongoing episodes of psychosis Severe craving Protracted dysphoria Anhedonia

23. Steps to Address Treatment Needs of MA Users Psychiatric/Professional Mental Health Staffing Add Treatment Programming for Women Exposed to Violence and Their Kids Training, Training, Training

24. Medications Currently, there are no medications that can quickly and safely reverse life threatening MA overdose. There are no medications that can reliably reduce paranoia and psychotic symptoms, that contribute to episodes of dangerous and violent behavior associated with MA use.

25. Medications considered for Meth Negative ResultsUnder Consideration ImipramineBupropion DesipramineModafinil TyrosineTopirimate OndansetronDisulfiram FluoxetineLobeline GabapentinAripiprazole

26. Bupropion: An efficacious pharmacotherapy? Newton et al 2005 Bupropion reduces craving and reinforcing effects of meth Elkashef (recently completed) Bupropion reduces meth use in an outpatient trial, with particularly strong effect with less severe users.

27. Special treatment consideration should be made for the following groups of individuals: Female MA users (higher rates of depression; very high rates of previous and present sexual and physical abuse; responsibilities for children). Injection MA users (very high rates of psychiatric symptoms; severe withdrawal syndromes; high rates of hepatitis). MA users who take MA daily or in very high doses. Homeless, chronically mentally ill and/or individuals with high levels of psychiatric symptoms at admission. Individuals under the age of 21. Gay men (at very high risk for HIV and hepatitis).

28. Treatment Options

29. CSAT Tip #33 A useful resource that presents a review of the existing knowledge about treatment effectiveness with stimulant users. The following issues should be addressed by the clinical staff: –Meth and sexual behavior –Meth and weight gain –Meth and ongoing paranoia

30. An Unfortunate, But Common Treatment Process Detox- Only Admissions Detox Residential Rehab IOP Rehab Outpatient Cont Care AA -Tele Monitoring Tele Monitoring

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

32. An Ideal Model – No Discharge Substance Abusing Patient Regular Performance Measurement Hospital Detox Residential Rehab IOP Rehab Outpatient Cont Care AA -Tele Monitoring Tele Monitoring

33. Behavioral/Cognitive Behavioral Treatments Cognitive/Behavioral Therapy-CBT Motivational Interviewing-MI Contingency Management-CM 12 Step Facilitation Therapy Community Reinforcement Approach-CRA Matrix Model of Outpatient Treatment

34. Cognitive Behavioral Therapy Based upon Social Learning Theory (Bandura and others) Also referred to as Relapse Prevention Therapy Applied to treatment of alcoholism, cocaine dependence, nicotine dependence and marijuana abuse.

35. Cognitive Behavioral Therapy Key Concepts –Encouraging and reinforcing behavior change –Recognizing and avoiding high risk settings –Behavioral planning (scheduling) –Coping skills –Conditioned “triggers” –Understanding and dealing with craving –Abstinence violation effect –Understanding basic psychopharmacology principles –Self-efficacy

36. Motivational Interviewing Based upon Prochaska and DiClemente Stages of Change Theoretical Model Also referred to as Motivational Enhancement Therapy Applied with many substances, data primarily with alcoholics Major Publications/Studies: Miller and Rollnick, 1991; Project MATCH

37. Motivational Interviewing Basic Assumptions –People change their thinking and behavior according to a series of stages –Individuals may enter treatment at different “stages of change” –It is possible to influence the natural change process with MI techniques –MI can be used to engage individuals in longer term treatment and to promote specific behavior changes –Confrontation of “denial” can be counterproductive and or harmful to some individuals

38. Motivational Interviewing Key Concepts –Empathy and therapeutic alliance –Give feedback and reframe –Create dissonance –Focus of discrepancy of expected and actual –Reinforce change –Roll with resistance

39. Community Reinforcement Approach Basic assumptions –Drug and alcohol use are positively reinforced behaviors. They can be reduced/eliminated by proper application of behavioral techniques. –To successfully build an effective intervention, some techniques should focus on reducing drug and alcohol use and others should focus on acquisition of new incompatible behaviors

40. Community Reinforcement Approach Key concepts –Behavioral analysis and teach conditioning information. –Positive reinforcement with vouchers for drug free urine samples –Behavioral marriage counseling –Shape and reinforce new behavioral repetiore. –Coping skill/Drug refusal skill training –Vocational Counseling –Frequent urine testing

41. Contingency Management Basic Assumptions –Drug and alcohol use behavior can be controlled using operant reinforcement procedures –Vouchers can be used as proxy’s for money or goods –Vouchers should be redeemed for items incompatible with drug use –Escalating the value of the voucher for consecutive weeks of abstinence promotes better performance –Counseling/therapy may or may not be required in conjunction with CM procedure

42. Contingency Management Key concepts –Behavior to be modified must be objectively measured –Behavior to be modified (eg urine test results) must be monitored frequently –Reinforcement must be immediate –Penalties for unsuccessful behavior (eg positive Ua) can reduce voucher amount –Vouchers may be applied to a wide range of prosocial alternative behaviors

43. 12 Step Facilitation Therapy The therapist acts as a resource and advocate of the 12-Step approach to recovery: –Explains the AA view of alcoholism, analyzes slips and resistance to AA in terms of disease of alcoholism and denial. –Introduces AA-Steps and concepts by applying these to patient history –Advocates Reliance on fellowship of AA and its role in ongoing recovery – 12 sessions 1:1 12 step Facilitation Manual can be downloaded from the NIAAA web site Book: 12 Step Facilitation Handbook …..by Nowitzki and Baker

44. Matrix Model of Outpatient Treatment Organizing Principles of Matrix Treatment Structured intensive outpatient approach delivered over a 16 week period, with ongoing aftercare. Matrix “treatment” is a process of “coaching”, educating, supporting and reinforcing positive behavior change. Positive reinforcement used extensively to promote treatment engagement and retention. Verbal praise, group support and encouragement other incentives and reinforcers.

45. Matrix Model of Outpatient Treatment Organizing Principles of Matrix Treatment Non-judgmental, 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.

46. Matrix Model of Outpatient Treatment Organizing Principles of Matrix Treatment Accurate, understandable, scientific information used to educate patient and family members Behavioral strategies used to promote cessation of drug and alcohol use Promote and reinforce participation in non-drug related activities Cognitive-Behavioral strategies used to promote cessation of drug use and prevention of relapse

47. 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

48. Treatments for Meth Users with Empirical Support

49. Why CM? It has proven effective for treating every type of substance abuse disorder to which it has been applied (e.g., Higgins & Silverman, 1999) It is one of the most effective treatments for cocaine abuse (e.g., Rawson, R.A. McCann, M.J, Huber, A. Shoptaw, S., Farabee, D. Reiber, C. and Ling, W., 2002) A laboratory model of CM suggests that methamphetamine abusers will forgo opportunities to self-administer methamphetamine in exchange for small monetary reinforcers (e.g., Roll & Newton, In press)

50. Roll, et al., American Journal of Psychiatry, In Press CM+TAUTAU Total # of negative samples provided

51. Roll, et al., American Journal of Psychiatry, In Press CM+TAUTAU Longest Duration of Abstinence

52. Roll, et al., American Journal of Psychiatry, In Press CM + TAU TAU

53. Conclusions CM appears to increase the abstinence rates when combined with psychosocial treatments Suggests CM should be an integral part of methamphetamine use disorder treatment modalities

54. Contingency Management: A Meta-analysis A recent meta-analysis reports that CM results in a successful treatment episode 61% of the time while other treatments with which it has been compared result in a successful treatment episode 39% of the time (Prendergast, Podus, Finney, Greenwell & Roll, submitted)

55. Methamphetamine Outcomes from CTN 006

56. The Matrix Model MondayWednesdayFriday Early Recovery Skills Weeks1-4Family/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

57. Route of Methamphetamine Administration

58. Changes from Baseline to Treatment-end

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

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

61. Mean Number of Weeks in Treatment

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

63. Figure 4. Percent completing treatment, by group

64. 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

65. Urinalysis Results Results of Ua Tests at Discharge, 6 months and 12 Months post admission ** Matrix 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

66. My sexual drive is increased by the use of … (Rawson et al., 2002)

67. My sexual pleasure is enhanced by the use of … (Rawson et al., 2002)

68. My sexual performance is improved by the use of … (Rawson et al., 2002)

69. Female Methamphetamine Users: Social Characteristics and Sexual Risk Behavior Semple SJ, Grant I, Patterson TL Women and Health Vol. 40(3), 2004

70. Introduction Research on female meth users has not kept pace with the increased number of women who use this drug. To date, the majority of meth studies have focused on gay and bisexual men; within this population, meth is reputed to be a party drug that enhances sexual pleasure.

71. Demographics (n=98) Ethnicity –44% Caucasian –33% African American –16% Latina –2% Native American –5% Other Education –96% had less than a college education Marital Status –54% had never been married Employment –77% were unemployed

72. Sexual Partners of Meth-Using Women On average women had 7.8 sexual partners in a two- month period (SD=10.7, range 1-74). 84% had casual partners during the past two months. –90% of all casual partners were reported to be meth users. 31% had an anonymous partner in the past two months. –76% of anonymous sex partners were meth users. No spouses or live-in partners were reported to be HIV- positive.

73. Sexual Risk Behavior Participants engaged in an average of 79.2 sex acts over a two-month period. Most sexual activity was unprotected. The average number of unprotected and protected sex acts over the two-month period was 70.3 and 8.8, respectively. In terms of unprotected sex: –56% of all vaginal sex acts were unprotected –83% of all anal sex acts were unprotected –98% of all oral sex acts were unprotected

74. Disadvantages The women in this study were also characterized by high levels of personal and social disadvantage. –Had modest levels of education –Unstable living arrangements –Low income –Low rates of employment –High rates of psychiatric diagnoses As demonstrated by in previous research, women who experience these forms of disadvantage may be more likely to engage in both drug use and HIV risk behaviors.

75. Behavior Symptom Inventory (BSI) Scores at Baseline

76. Beck Depression Inventory (BDI) Scores at Baseline

77. Self-Reported Reasons for Starting Methamphetamine Use

78. Craving by Route P<.05

79. Treatment Length by Route P<.05

80. MA-Free Samples by Route P<.05

81. BSI Psychiatric Symptoms by Route P<.05 Positive Symptom Total (PST)

82. Sample Characteristics 305 Adolescents (13-18 years old) Average Age ~ 16yrs old (sd=1.138) Gender: 70.2% Males Ethnicity: 55.3% White & 33.1% Latino

83. Drug of Choice: N=305 Methamphetamine 74 (24.3%) Pot 149 (48.9%) Alcohol 24 (7.9%) Methamphetamine & Pot 9 (3%) Methamphetamine & Alcohol 6 (2%) Pot & Alcohol 26 (8.5%) Cocaine 6 (2%) Opiates (Heroin) 3 (1%) Other 8 (2.6%)

84. Drug Use by Gender

85. Treatment History by Drug Use Total (N=275*) Total (N=275*) *30 Missing %Completed % Not Completed 139(50.5%)136(49.5%) METH(n=85) 37 (43.5%) (43.5%)46(54.1%) OTHER(n=190) 102 (53.7%) 88 (46.3%) (46.3%)

86. Psychological Distress Missing Data* Total % Yes % Yes(n=275)OTHER(n=196) METH USERS (n=79) Depression*128 (46.5%) (46.5%) 83 (42.6%) 45(57.7%) Suicidality Attempted Suicide Does not want to live Like to injure yourself 72 (26.2%) (26.2%) 48 (24.5%) 24 (30.8%) Psychopathology* Paranoid Feelings Losing Mind Hearing Voices 87(31.6%) 53 (27.0%) 34 (43.0%) P<.05

87. Prevalence of Hepatitis C in the U.S. Hepatitis C is the most common blood borne infection in the United States (CDC, 1998). Hepatitis C virus (HCV) is efficiently transmitted via injection drug use, which is the primary risk factor for acquiring HCV (CDC, 2003). The vast majority of injecting drug users in the United States already are infected with HCV (Hagan et al., 2001) with prevalence estimates of 90% infection among individuals who injected for 5 or more years (Garfein et al., 1996).

88. Hepatitis C by Route P<.05

89. Motivations Associated with Meth Use among HIV+ MSM Meth makes sex more pleasurable Meth facilitates sexual experimentation Meth helps participants to cope with an HIV+ diagnosis Meth use provides a temporary escape from being HIV+ Meth use helps the individual to manage negative self-perceptions and social rejection associated with being HIV+ SOURCE: S. Semple, et al. (2002) Journal of Substance Abuse Treatment, 22: 149-156

90. Do meth users stop on their own? Meth use via intranasal or oral routes may D/C meth on their own Oral and intranasal use until a decade ago Meth users take 7-10 years to enter Rx Large majority now smoke or inject. They don’t stop on their own. These users are now entering AOD system. Treatment demand is and will expand. Many meth users show up in primary care and mental health systems

91. Current Status of Meth Research Brain imaging research is impressive, valuable and quite well developed programs Research on meth and kids in labs needed Research on meth and adolescent treatment needed Treatment research developing slowly –No medications available and moving ahead slowly –Few studies of behavioral treatments