Medication Assisted Treatment for Alcohol and Opioid Dependence

1. Medication Assisted Treatment for Alcohol and Opioid Dependence Larissa Mooney, M.D. Assistant Professor of Psychiatry UCLA Integrated Substance Abuse Programs April 25, 2012

2. Objectives • Introduction to addictive disorders (SUDs) • Epidemiology • Neurobiology • Health effects of alcohol and opioid use disorders • Pharmacological treatments within drug classes: • Alcohol • Opioids

3. Introduction • Addiction is a chronic, relapsing brain disease characterized by compulsive use despite harmful consequences • Pharmacotherapy as part of multimodal treatment plan • Treatment approaches: • Medications (Bio) • Therapy, lifestyle changes (Psycho-Social)

4. 12-Month and Lifetime PrevalenceRates - NESARC • Alcohol dependence • 12 Mo: 4.3% • Lifetime: 12% (30% for AUDs) • Annual mortality: ~100,000 • Other (non-nicotine) drug dependence • 12 Mo: 0.6% • Lifetime: 2.7% • Annual mortality: 17,000 Hasin et al., 2007; Compton et al., 2007

5. Addiction Risk Factors

6. Neurobiology of Addiction • Reward system: dopamine pathway • Natural vs. drug rewards • Dopamine release: pleasure and reinforcement • Dopamine projections to brain reward centers and prefrontal cortex (PFC) • Process of addiction causes dysfunctional learning and memory and maladaptive behavioral patterns • Impaired decision-making, loss of control • Altered neurobiology: relapse risk even after extended periods of abstinence

7. Reward pathway -- mesolimbic dopamine system

8. Pharmacotherapy in Substance Use Disorders • Treatment of withdrawal (“detox”) • Treatment of psychiatric symptoms or co-occurring disorders • Reduction of cravings and urges • Substitution therapy

10. Alcohol-Related Impacts • 3rd leading cause of preventable death • 15-30% of primary care and hospitalized • 40% trauma patients with BAL = 0.1 • Trauma is leading cause of death < age 40 • 40% of MVA deaths • 2,000,000 injuries • Life span of AUD cut by 15 years • 15% will develop ETOH cirrhosis

11. Cardiovascular Consequences of Alcohol Hypertension Cardiomyopathy (enlarged heart) Coronary heart disease (CHD), CHF Arrhythmias Low/moderate use: protective

12. Hepatic Consequences of Alcohol Fatty liver Alcoholic hepatitis Cirrhosis Women: earlier onset of illness

13. Other Medical Consequences Pancreatitis Anemia Neuropathy Osteoperosis Wernicke-Korsakoff (thiamine deficiency) Fetal Alcohol Syndrome (spectrum disorder) Cancers: breast, head and neck, stomach, esophageal, colon, liver

14. Alcohol Effects: Neurotransmitters +GABA the main inhibitory neurotransmitter:slows you down -glutamate the main excitatory neurotransmitter: speeds you up endogenous opioids make you euphoric and feel no pain dopamine makes you happy

15. Medications for Alcohol Dependence • FDA-Approved: • Disulfiram (Antabuse) • PO naltrexone (Revia) • IM naltrexone (Vivitrol) • Acamprosate (Campral) • Non-FDA-approved: • Topiramate (Topamax) • Ondansetron (Zofran) • Quetiapine (Seroquel) • Baclofen

16. Disulfiram (Antabuse) • FDA approved 1951 • Dosing: 250mg-500mg qd • Mechanism: inhibits aldehyde dehydrogenase, causing buildup of acetaldehyde with alcohol ingestion: • Flushing, nausea, vomiting, dizziness, dyspnea, diaphoresis, headache, palpitations • In severe cases: arrhythmias, seizures, coma, cardiovascular collapse

17. Disulfiram (Antabuse) • Reactions may occur 1-2 weeks after last dose • Caution: “hidden” alcohol in perfumes, mouthwash, cough medicines, desserts, sauces, salad dressings • Side effects: fatigue, headache, hepatitis, psychosis (dopamine), neuritis, rash, aftertaste • Most likely to benefit: highly motivated and directly observed patients

18. Naltrexone (Revia) • FDA approved 1994 • Dosing: 50 mg PO qd (start at 25 mg qd) • Mechanism: μ-opioid antagonist • Decreases positive reinforcing effects • Decreases cue- and alcohol-induced cravings • Side effects: nausea, dysphoria, increased LFTs • Results: fewer drinking days, less alcohol consumed, decreased craving

19. Research on Naltrexone Results: Two studies submitted for FDA approval. In both studies, participants treated with naltrexone had a greater reduction in relapse during the entire study than those treated with placebo. * statistically significant

20. IM Naltrexone (Vivitrol) • FDA approved 2006 • Dose: 380 mg IM q 4 weeks • Enhanced compliance • Stop drinking 7 days prior (ideal) • Mechanism: opioid antagonist • Results: Decreased heavy drinking days, decreased frequency of drinking

21. FDA Approved 2004 Dose: 666mg PO tid Renal excretion Structural analog of GABA Mechanism: NMDA receptor modulation Restores GABA-glutamate balance Blocks “negative” reinforcement Acamprosate (Campral)

22. Start post-detox (ideal) Side effects: diarrhea, abdominal discomfort Results: increased time to relapse, increased total abstinence, reduced drinking days Acamprosate (Campral)

23. Research on Acamprosate Results: In all three studies, participants treated with acamprosate were able to maintain complete abstinence more frequently than those treated with placebo Study * statistically significant

24. Results: In all three studies, participants treated with acamprosate had a greater reduction in the number of drinking days during the entire study than those treated with placebo. Research on Acamprosate * statistically significant

25. Results: In all three studies, participants treated with acamprosate were able to regain complete abstinence after one relapse more frequently than those treated with placebo. Research on Acamprosate Relapse * statistically significant

28. Public Health & Risk Behavior Problems • Tuberculosis • IDUs high risk • STDs • Gonorrhea, chlamydia, syphilis, herpes • HIV/AIDS • HBV • HCV

29. Opioid Dependence: Needle-Related Problems • Abcess • Cellulitis • Subacute bacterial endocarditis • Necrotizing fasciitis • Botulism

30. Treating Opioid Dependence: Aims • Detoxification: • Opioid-based (methadone, buprenorphine) • Non-opioid based (clonidine, supportive meds) • “Rapid detox” • Relapse prevention: • Agonist maintenance (methadone) • Partial agonist maintenance (buprenorphine) • Antagonist maintenance (naltrexone, Vivitrol) • Lifestyle and behavior change

31. Opioid Detoxification • Medications used to alleviate withdrawal symptoms: - Opioid agnonists (methadone, buprenorphine) - Clonidine (alpha-2 agonist) • Dose: 0.1 mg PO tid (increase as tolerated) • Caution: hypotension - Other supportive meds • anti-diarrheals, anti-emetics, ibuprofen, muscle relaxants, BDZs

32. Opioid Substitution Goals • Reduce symptoms & signs of withdrawal • Reduce or eliminate craving • Block effects of illicit opioids • Restore normal physiology • Promote psychosocial rehabilitation and non-drug lifestyle

33. Methadone: Clinical Properties • Orally active synthetic μ agonist • Action: CNS depressant/ Analgesic • Long half-life, slow elimination • Effects last 24 hours; once-daily dosing maintains constant blood level • Prevents withdrawal, reduces craving and use • Facilitates rehabilitation • Clinic dispensing limits availability

34. Buprenorphine for Opioid Dependence • FDA approved 2002, age 16+ • Mandatory certification from DEA (100 pt. limit) • Mechanism: partial mu agonist • Office-based, expands availability • Analgesic properties • Ceiling effect • Lower abuse potential • Safer in overdose

35. Buprenorphine Formulations • Sublingual administration • Subutex (Buprenorphine) -2mg, 8mg • Suboxone (4:1 Bup:naloxone) -2mg/0.5 mg , 8mg/2mg • Dose: 2mg-32mg/day

36. IM Naltrexone (Vivitrol) • FDA approved 2010 • Dose: 380 mg IM q 4 weeks • Enhanced compliance • Must be opioid-free for 7-10 days • Mechanism: opioidantagonist • Blocks effects of opioids for 4 weeks

37. Challenges for Dually Diagnosed • Patients with CODs are more likely to have: • Increased severity of mental illness • Medication noncompliance • Worse treatment prognosis (more severe course, etc.) • Lower income and resources • Worse physical health • Increased risk of incarceration Buckley 2006, J Clin Psychiatry; SAMHSA 2007

38. Traditional Treatment Models • Mental health and substance use disorders treated separately • “I can’t treat your depression until you take care of your alcohol problem” • Sequential treatment of SUD/psychiatric d/o • Parallel treatment • More recent evidence: supports integrated treatment

39. In Conclusion • Addiction is a serious, chronic and relapsing disorder, but treatments are available • Medications should be considered as part of a comprehensive treatment plan, addressing both disordered physiology and disrupted lives • Medications should be considered for treatment of: psychiatric sx’s, addictive d/o’s, and co-occurring d/o’s

40. Thank you! Larissa Mooney, M.D. UCLA Integrated Substance Abuse Programs lmooney@mednet.ucla.edu