Acknowledgements: NIDA grants: R01DA 13636, ,

Transcription

1 Myths an nd Facts about Medication Assisted Treatment Robert P. Schwartz, M.D. Fi Friends Research Institute t Acknowledgements: NIDA grants: R01DA 13636, ,

2 FDA-approved Medicatio ns: Nicotine Dependence Bupropion (Wellbutrin, Zyban) Nicotine Therapy (Gum, Patch, Lozenge, Inhaler) Varenicline (Chantix)

3 12-Month Smoking Abstinence Rates (Jorenby e t al., 1999)

4 Randomized Comparative Effectiveness Trial (Piper et al, 2009) Placebo Patch Lozenge Patch + Lozenge SR Bupropion SR Bupropion + Lozenge

5 FDA-approved Medicatio ons: Alcohol Dependence Disulfuram (Antabuse) Oral naltrexone (Revia) Injectable extended release naltrexone (Vivitrol) Acamprosate (Campral) Alcohol withdrawal: benzodiazepines (e.g., valium, librium)

6 FDA-approved Medications: Cocaine & Methamph etamine Dependence None Several medications have shown promising results Several compounds are under development

7 FDA-approved Medicatio ons: Opioid Dependence Methadone Buprenorphine (Subutex) Buprenorphine/Naloxone (Suboxone) Oral Naltrexone (Revia)

8 FDA-approved Medications: Opioid Dependence Opioid Agonists 1) Full agonist: Methadone (oral) 2) Partial agonist: Buprenorphinee (sublingual) Opioid Antagonist 3) Naltrexone (oral)

9 What is the Difference Between an Opioid Agonist & Antagonist? 100 Opioid Effect Methadone Buprenorphine Naltrexone Dose of Opioid

10 Opioid Agonists

11 Methadone and Buprenorphine Activate the opioid receptors Buprenorphine s opioid effect plateaus at higher doses, which explains its superior safety profile Reduce heroin craving Alleviate withdrawal Block heroin s euphoric effe ects by occupying the receptor

12 Effects of Buprenorphine Dose on µ-opioid Receptor Availability MRI Bup 0 mg inding otential Bmax/Kd) Bup 2 mg 4 - Bup 16 mg 0 - Bup 32 mg

13 Buprenorphine Blocks Dilaudid s Effects Change In Opioid Effects Buprenorphinee Dosage (mgs.)

14 What is the Difference Between Heroin Addiction and Opioid Agonist Treatment? Route Onset Euphoria Dose Cost Duration Legal Heroin Addiction Injected Immediate Yes Unknown High 4 hours No Agonist Treatment Oral or Sublingual Slow No Known Low 24 hours Yes Lifestyle Chaotic Normal

15 Where Can Patients Get Methadone & Buprenorphine Treatment? Opioid Treatment Programs (OTPs) - Methadone or buprenorphinee - Counseling & drug testing - Clinic administered dosing - Take home doses contingent on performance Outpatient Counseling Programs - Buprenorphine only - Counseling & drug testing - Clinic administered dosing in itially and then by prescriptions

16 Physician Office-B Based Treatment - Buprenorphine with physician monitoring - Referral to counseling & drug testing - Doses self-administered through prescriptions - Widely used internationally - In US often limited to insured patients

17 How Long Should Patients Stay on Buprenorphine or Methadone Treatment? t? Shorter-term: Detoxification Longer-term: Maintenance Length of treatment should be individually determined by the patient and physician

18 How Effective is Detoxification with Opioid Agonists? Reducing withdrawal symptoms Helps some patients remain drug-free after detoxification Most patients relapse quickly after medication is discontinued 29% success at completion of 2 week detox (Ling et al., 2005) Low success rate for both inpatient & outpatient detox Relapse is associated with increased risk of overdose death and recidivism

19 How Effective is Opioid Agonis st Maintenance Treatment? Many studies show its effectiveness in reducing: - Heroin use - Criminal activity - HIV risk behavior

20 What are the Characteristics of Effective Maintenance Treatm ment? Higher doses (individualized to patients needs) Longer time in treatment Psychosocial services of appropriate intensity it & duration

21 Higher Methadone Dose is Associated with Less Frequent Heroin Use (Ball & Ross 1991) Days of Use < Methadone Dose (mgs)

22 Longer Time in Methadone Treatment Associated with Fe ewer Days of Crime (Ball & Ross 1991) Activity Days Criminal # Pre-Tx 1 year 4 months 2 years 3 years s

23 Interim Methadone Reduces Positive Heroin Drug Tests Compa ared to Waiting List % positive Interim Wait List Baseline 4-Month 10-Month

24 Mean Number of Pos st-enrollment Arrests Months* 12 Months 24 Months * p <.02 IM Control

25 Severity Rating Scale of Arrest Charges Non-Severe 1: Baudy House-Prostitution, Possession of Marijuana 2: Pimping, Trespassing, Failure to Obey, Disorderly Conduct 3: Theft Less than $500, Malicious destruction of property p more than $500, Forgery, Uttering 4: Theft greater than $500, Carrying a handgun, Drug sales Severe 5: Burglary, Second degree assault, Battery 6: Robbery with a deadly weapon, Assault first degree 7: Attempted first degree murder, Rape

26 Most Arrests of Heroin Add dicted Individuals (In or Out of Treatment ) Are for Non-Severe Charges Charge Severity Interim Waiting List Not arrested 84% 79% Non-severe (1-4) 13% 20% Severe (5 7) 3% 1%

27 Discharge from Methadone Treatment is Associated with Increased Drug Injection (Ball & Ross 1991) % inject ting In Treatment 1 month 4 months 9 months 12 months

28 Methadone Treatment Reduces Likelihood of HIV Infection (Metzger et al., 1993) 35% e Positiv % HIV 30% 25% 20% 15% 10% 5% 0% Treatment In Out Base 6 mo 12 m 18 m seline months months months

29 Myths & Beliefs about Methadone Treatment I don t believe in methadone It s just substituting one drug for another You have to stay on it for lif fe Methadone withdrawal is worse than heroin withdrawal It eats your bones and rots your teeth I won t let probationers com mplete probation until they re off methadone

30 Buprenorphine/naloxone vs. Buprenorphine Alone Combination of buprenorphine with naloxone (Suboxone): - Sublingual buprenorphine is well absorbed - Naloxone decreases Suboxone s abuse potential - injection precipitates withdrawal Buprenorphine Alone (Subutex): Rare indications for use

31 Buprenorphin ne Treatment Buprenorphine more effective than placebo Buprenorphine as effective as moderate doses of methadone

32 Buprenorphine & High Dose Methadone Increase Time in Treatment Pe ercent of Pa atients LAAM Buprenorphine High Dose Methadone Low Dose Methadone From: Johnson et al., 2000

33 30 Self-Reported Opiate Use 25 Mean Fre equency LAAM Buprenorphine High Dose Methadone Low Dose Methadone Study Week From: Johnson et al., 2000

34 Opioid Positive Urine Specimens ive Pe ercent Posit LAAM 20 Buprenorphine High Dose Methadone Low Dose Methadone From: Johnson et al., 2000

35 No Myths About Buprenorphine (Yet) (Schwartz et al., 2008) Out-of-treatment heroin addicts hold a more favorable view of buprenorphine than of methadone. Some believe its easier to get methadone off buprenorphine p than Buprenorphine may attract people to treatment who otherwise would not enter

36 Agonist Treatment In Criminal Justice System These medications can be used in probation, parole and drug courts Although not uniformly available Highly effective at reducing drug use and criminal behavior Unfortunately agonist treatments often are not continued upon incarceration

37 Treating Heroin Addicted Inmates Most heroin-addicted inmates in the US do not receive opioid agonist treatment while incarcerated (Rich et al., 2995) Although it is widely used internationally Australia, Canada, Europe, Iran and elsewhere (Dolan 2001) Re-addiction upon release is common Re-addiction may be accompanied by: Increased criminal activity Re-incarceration Overdose death

38 Arrestees respon nse to withdrawal: Cold turkey in Jail * Sought non-opioids id from medical staff Self-injury to obtain stronger r medications Faked symptoms to obtain medications Obtained drugs or meds from cell-mates * Mitchell et al., (2009)

39 I mean, I went through the detox from the methadone and it was horrible. I was so sick. The only thing they gave me at jail was Clonidines and somet thing else... for my stomach, because I kept vomiting so much. And I never want to go on that (methadone) again becau use that, I was, I literally wanted to die because of how much pain I was in.

40 Agonist Treatment in Jails Uses of Agonist Treatment Detoxification from heroin (if desired/indicated) Initiate opioid agonist trea upon release) tment (which can be continued Continue agonist treatment for arrested patients

41 Community Tre eatment Status Entered Community Trea tment Completed 1-year 100% 80% M = 23 days 60% 40% 20% M = 91 days M = 166 days 0% CO C+T C+M Kinlock et al., 2009

42 Drug Testing 1-Y Year Post Release Opioid positive* Cocaine positive** 100% n = 32 n = 39 80% 60% 40% 20% 0% CO C+T n = 44 C+ M

43 Pris sons Uses of Agonist Medications Initiate treatment for in-prison heroin users Initiate treatment for in-prison abstainers who are nonvent relapse upon tolerant but want to prev release

44 Opioid Agonist Tre eatment: Summary Methadone and buprenorphinee are FDA-approved Block the euphoric effects of heroin Both can be provided in OTPs Buprenorphine can be providedd in physician offices & clinics Reduce heroin use, HIV risk and criminal behavior Longer treatment duration and with better outcomes higher dose are associated Can be provided to probatione rs, parolees, Drug Courts, and inmates

45 II. Opioid id Antagonists

46 Opioid Antagonist Treatment Oral Naltrexone Highly effective pharmacologically Hampered by poor patient adhere ence Useful for highly motivated patients Depot IM formulation (Vivitrol ) FDA-approved only for alcohol dependence Under study for opioid dependence Opioid blockade last about 30 days

47 Randomized Trial with Federal Probationers: % Drug Tests Positive at 6 month follow-up (Cornish et al., 1997) Drug Oral Nltx Control (N=34) (N=17) Opioid 8% 30% Cocaine 33% 49% Alcohol 2% 4%

48 Re-Incarceration at 6 months (Cornish e t al., 1997) 100 subject ts Percent % 56% 0 Naltrexone Control

49 Depot Naltrexone Study (O Brien & Colleagues) 400 adult probationers and parolees at five sites - Excludes individuals wanting opioid agonist treatment Counseling available to all Random assignment: Naltrexone v. No medication Medication for six months participants 12 & 18-month hfollow-up: drug use & arrest

50 Summary Opioid antagonists are effective when taken but have poor adherence Depot naltrexone (if approved by the FDA for opioid dependence) may become an alternative for select patients who do not want opioid agonists Opioid agonists and antagonists are underutilized in both community and criminal justice settings