Pharmacotherapy of Addictions

1. Pharmacotherapy of Addictions Timothy Fong MD Addiction Medicine Clinic 310.825.1479 tfong@mednet.ucla.edu

2. Overview 1. Pharmacotherapy of Addictions A. Substance Use Disorders Alcohol Opiates Stimulants Nicotine Marijuana Sedative-Hypnotics

3. Overview (II) 1. Pharmacotherapy of addictions B. Impulse Control Disorders i. Pathological Gambling ii. Compulsive Shopping iii. Compulsive Sexual Behaviors

4. Drug Use Patterns Marijuana – 12 million Cocaine – 2 Million Hallucinogens – 1.3 million Heroin – 800,000 1,200 people died in LA in Emergency Rooms related to drugs in 2000 (officially)

5. Outcomes of Drug Abuse 2 million people die each year in the US -430,000 due to tobacco -100,000 due to alcohol -16,000 for illicit drugs

6. Cost of Drug Abuse Economic costs of Alcohol and Drug Abuse ( NIDA 1992) $245 Billion Dollars - Treatment (30%) - Productivity losses (20%) - Crime (40%) - Deaths (10%)

7. Costs of Drugs 1988 – 1995 $57 Billion dollars spent on drugs (does not include alcohol or nicotine) $20 billion spent on cigarettes / year

8. Goals of Medication Tx in Addictions 1. Abstinence (or Reduction) 2. Treat or prevent withdrawal symptoms 3. Reduces urges/cravings 4. Diminish “the high” / make it less worthwhile 5. Minimize relapses time and intensity 6. Treat comorbid disorders

9. Medication Strategies • Agonist Substitute effects of drug • Antagonist Block the effects of drug • Deterrent Medications (aversive) • Reduce Drug Intake Target cravings, reinforcement

10. Alcohol Dependence • Disulfiram (Antabuse) • Naltrexone (Revia) • Topiramate (Topamax) • Acamprosate (Campral)

11. Antabuse FDA Approved 1951 MOA: Inhibits aldehyde dehydrogenase, increasing acetaldehyde. Evidence: So-so Most likely to benefit: highly motivated patients, directly observed patients,

13. Antabuse Dosing: 250 mg – 500 mg qd Side effects: Nausea, metallic taste,dysphoria, fatigue, hepatitis, psychosis (dopamine) Effects can last 72 hours after last dose

14. Naltrexone (Revia) FDA Approved 1994 MOA: Opiate Antagonist decrease positive, reinforcing effects increase negative aspects decrease craving from first dose (prime) decrease craving from cues

15. Naltrexone Starting: (50 mg or 100 mg) 25 mg and increase by 25 mg week until SE or target dose of 200 mg SE: dysphoria, nausea, increased LFTs Costly Modest effect, at best Depot formulation coming . . .

16. Topiramate MOA: blocks NA channels, augments GABA, inhibits glutamate Early phase of investigation may reduce drinking days reduce cravings improve quality of life measures

17. Topiramate (Topamax) Dosing Strategy: 25 mg and then increase by 25 mg every week (target dose = 200 mg or higher) Side Effects: cognitive dulling, weight loss, fatigue, somnolence

18. Acamprosate (Campral) MOA: Made from taurine ; NMDA receptors in the glutamate system – generally inhibitory Not much action on GABA Dose: 333mg bid – 333mg tid (1,998 mg) Notes: European data – 4500 patients, FDA approved Sept 2004 Relapse Prevention, targets “negative reinforcement” SE: Diarrhea, rash.

20. Opiate Dependence • 800,000 meet criteria for dependence but 180,00 in treatment

21. Opiate Dependence • Methadone • Buprenorphine • LAAM • Naltrexone

22. Methadone

23. Methadone FDA Approved 1973 (detox and maintenance) MOA: Long-acting opiate, full agonist at mu receptor Notes: 179,000 actively in treatment No notable tolerance

24. Methadone Methadone Clinics Starting dose – 20 mg – 40 mg and up to no more WD sxs Maintenance Dose: 80-120 mg Side effects: prolonged QT with increasing dose

25. LAAM Levo-alpha-acetylmethadol “Long-acting methadone” No longer made Prolonged QT

26. Naltrexone (for Opiates) Purported to reduce pleasure from opiates Only 15% stay in treatment Doesn’t seem to reduce cravings in opiate dependents Best for highly motivated patients or pregnancy Overdose risk increased after d/c

27. Buprenorphine (Suboxone, Subutex) FDA Approved 2003 MOA: Partial Agonist; tight binding Ceiling Effects Schedule III Need special DEA number/waiver

28. Buprenorphine Formulations: Sublingual Subutex (Buprenorphine) 2mg, 8mg Suboxone (Bup + Naloxone 4:1) 2mg, 8mg

29. Buprenorphine Starting (Detox) Wait until opiate wd starts then give first dose (30-60 min until effect) starting doses 8mg –16 mg until wd sx are gone maintenance: 16-24 mg qd maximum: 32mg qd

30. Buprenorphine Notes: Office based but needs support Indicated for detox and maintenance Good for about a year 30 patient limit Some effectiveness for depression and cocaine dependence

31. Stimulant Dependence • Cocaine • Amphetamines

34. Classes of medications tried Dopamine agonists (amphetamines) Dopamine partial agonists (aripiprazole) Dopamine Reuptake Inhibitors (amantadine) Dopamine Metabolism Inhibitors (disulfiram) Dopamine Antagonists GABA Beta Blockers Opioids Antidepressants (SSRIs, TCAs) Cortisol Blockers

35. Stimulant Dependence Many strategies tried, none successful,yet consider: Baclofen (20 mg – 60 mg) heavy, binge users Bupropion (300 mg) – reduces craving? Selegiline (200 mg)– available as patch Buprenorphine – comorbid opiate dependence Amantadine 100 mg bid – bad withdrawal sx

36. Stimulant Dependence Abilify ACE-Inhibitors (dopamine) Antabuse (inhibits dopamine hydroxylase) Namenda

37. Novel Approaches Vaccinations Acupuncture Efficacy debatable

38. Nicotine Dependence • Gums (2mg or 4mg) • Lozenge (1mg) • Inhalers (4 mg) 6-12 per day • Nasal Spray (0.5 mg), max 40/day • Patch (7,14,21 mg) (passive) • Bupropion (300 mg) (primary effect) Cigarettes = 0.8 – 3 mg each

40. Nicotine Dependence Nicotine Replacement Therapies Increase quit rates 1.5 – 2x Meds + therapy = 15-30% quit rate Can combine passive and active NRT Duration of therapy – 8-12 weeks Effects of meds wane over time

42. Marijuana Dependence No RCT trials Anecdotes with fluoxetine, nefazadone. bupropion worsened wd sxs CB1 Antagonists CBT, MET and CM have the best evidence

43. Sedative-Hypnotics • http://www.benzo.org.uk • Fastest rising class of drugs of abuse • Practical pointers: • No refills • 2-4 months, max • Involve families • Printouts from pharamcies • Med logs

44. Sedative Hypnotics Principles for detox and maintenance: Substitute longer acting for shorter acting Prolonged taper to minimize withdrawal (months, if needed) Other Medications: Baclofen? Tegretol? Gabapentin? Topamax Depakote?

45. Sedative Hypnotics Notes: Prolonged Withdrawal states – mimic somatization, derealization, intense anxiety Not many studies to guide treatments Some patients remain on BZDs long-term but most should not . . .

46. Impulse Control Disorders • Pathological Gambling • Compulsive Shopping • Compulsive Sexual Behaviors (Sexual Addiction)

47. What is the role of meds in Impulse Control Disorders? • What are the goals of medications? • To treat comorbid disorders like depression or anxiety disorders • Can help with sleep, appetite and concentration • May reduce urges and cravings • Lays the groundwork for psychosocial treatments • NO MAGIC PILLS

48. “The Gambler” MGM 1974 Starring James Caan

49. Medications Strategies forPathological Gamblers Usually start with: SSRIs, (Paxil or Celexa) To reduce impulsive behaviors? Topiramate 25mg – 300 mg To reduce cravings/urges, block the high Naltrexone (50—200 mg)

50. Other Meds Gamblers who are hyperthymic or with cyclical gambling patterns: Mood Stabilizers To treat comorbid disorders / presenting symptoms use: SSRIs, ANL