Medication-Assisted Therapies for Addiction

1. Medication-Assisted Therapiesfor Addiction Michael Weaver, MD, FASAM Division of Addiction Psychiatry Virginia Commonwealth University Medical Center

2. Objectives Long-term pharmacotherapy Smoking Alcohol Opioids Methadone Buprenorphine Cases

3. Long-Term Pharmacotherapyfor Substance Dependence Doesn�t cure substance dependence Helps reduce drinking or episodes of use Achieve longer abstinence Works for a proportion of patients Goals Maintain abstinence Increase time to relapse Reduce intensity of binge if relapse occurs

4. Disease Model of Addiction Biologic basis Chronic course Relapses and remissions No cure Like other chronic diseases Treatable Individualize therapy Medications may help improve outcomes

5. Clinical Use of Pharmacotherapy Part of comprehensive plan that addresses psychological, social, & spiritual needs Do not use in place of counseling Works best in combination with psychosocial support

6. Behavioral Treatment Essential component of addiction treatment Multiple modalities available 12-Step Motivational Interviewing Relapse Prevention Contingency Management

7. Decisions, Decisions Whether to add long-term pharmacotherapy No pharmacotherapy for most classes of abused drugs Stimulants Hallucinogens Inhalants Marijuana Factors to consider Cost Availability Side effects Barriers Workplace drug testing Other meds taken Incarceration Motivation

8. Barriers Stimatization Science vs. dogma Evidence-based treatment vs. �drugs for drug addicts� 12-Step groups Becoming more progressive Methadone Anonymous is alternative Counselors Different experiences and biases Payors May be easier to justify med than counseling

9. What is the endpoint? Duration of most long-term pharmacotherapy is not indefinite Months to years Goal is stabilization Flexibility Individualized Allow for relapse

10. Smoking Cessation Pharmacotherapy Replacement nicotine patches nicotine gum nicotine lozenges nicotine nasal spray Antidepressant Zyban Partial agonist Varenicline (Chantix)

11. Nicotine replacement therapy Always combine with a behavioral therapy program Most available OTC, but all are expensive Reduces harmful effects of tobacco smoking Patients should not smoke while using

12. Nicotine Patch Highest success rate of available pharmacotherapies Nicoderm, Nicotrol, Habitrol, Prostep Most come in 3 strengths: 21, 14, & 7mg Start with 21mg patch for 6 wks, taper to 14 mg for 2 wks, finally 7 mg for 2 weeks Use new patch in different spot on upper trunk every 24 hrs

13. Nicotine Gum Nicorette - 2 or 4mg per piece doses Requires correct �chewing technique� -- don�t chew like regular chewing gum Chew 1 piece for 30 minutes every 1 to 2 hrs to prevent nicotine W/D Chew regularly for first month, then taper off over 6 months

14. Nicotine lozenges Commit, generics Suck on & move from side to side until dissolves 4 mg or 2 mg doses Flavor Mint, cherry, etc. �warming tingle� No comparison studies with patch or gum

15. Nicotine Nasal Spray Reduces nicotine craving & mimics pleasurable effects of nicotine 1 spray in each nostril, up to 40 times in 24 hours Use for up to 3 months May cause tearing, sneezing, & burning sensation in nose

16. Bupropion (Zyban) Bupropion 150mg sustained release pills Works on dopamine & norepinephrine receptors in the brain to decrease W/D Start pills 10-14 days before �quit date� Take daily for 3 days, then twice a day Continue pills for 8 - 12 weeks May cause insomnia, anxiety, or seizures Prescription includes behavioral program

17. Varenicline (Chantix) Nicotine partial agonist Start pills 10 days before quit date Increase dose Take for 12-24 weeks Includes behavioral program

18. Pharmacotherapy forAlcohol Dependence Disulfiram (Antabuse) Acamprosate (Campral) Naltrexone (ReVia, Vivitrol)

19. Disulfiram (Antabuse) Blocks acetaldehyde dehydrogenase Reaction to alcohol Flushing, palpitations, chest tightness Nausea, headache, anxiety Avoid slips or relapses Affects liver, even without alcohol Motivation is necessary Monitored dosing

20. Acamprosate (Campral) Alcohol dependence pharmacotherapy No drug interactions Minimal side effects Diarrhea Use caution in patients with suicidality

21. Mechanism of Action Neurochemical mechanisms that cause relapse to alcohol have not been elucidated Acamprosate Generally inhibitory to glutamatergic system in CNS Probably no single definitive molecular MoA Reduces symptoms of protracted abstinence Insomnia Anxiety restlessness

22. Clinical Use of Acamprosate Begin as soon as possible after the acute withdrawal period Does not treat withdrawal symptoms Dose: two 333 mg tablets 3 times daily with or without food Takes 5-7 days to reach effective level Treat for 12 months Effect sustained for at least 12 months more

23. Naltrexone (ReVia) Blocks opioid receptors Reduce craving Tablets or implantable pellets Reduces alcohol slips Used for opioids as well as alcohol

24. Injectable naltrexone (Vivitrol) Intramuscular injection of depot naltrexone given monthly Recently FDA approved for alcohol Administer in physician office, not at home Requires patient motivation

25. Opioid addiction treatments Ultra-rapid opioid detox Abstinence-based Narcotics Anonymous Residential (with or after detox) Antagonist maintenance Naltrexone Opioid maintenance Methadone Buprenorphine Heroin

26. Ultra-Rapid Opioid Detox Induce acute withdrawal with naloxone Patient under deep sedation/anesthesia Shortens course, but still uncomfortable High risk High cost Not recommended

27. Naltrexone implant Oral naltrexone compounded by pharmacy into pellet Inserted subcutaneously (minor surgery) Lasts for 1-3 months, may be replaced Antagonist maintenance Similar to oral/intramuscular naltrexone therapy Requires detoxification from opioids first Not approved by FDA

28. Maintenance pharmacotherapy for Opioids Long-acting medication in controlled setting Counseling Social services Avoid withdrawal & craving Reduce disease & crime Maintenance vs. detoxification

29. Methadone Opioid substitution therapy Harm reduction Individual Society Highly regulated Narcotic treatment programs must be licensed Very effective

30. Mechanism of Action Methadone is a mu opioid agonist No withdrawal symptoms No craving Long-acting Multiple metabolites Metabolized by Cytochrome P450 enzyme system drug interactions

31. Short-term detoxification Methadone given for <180 days Stabilization of withdrawal symptoms and behavior over weeks/months Taper over a few months Option for those who don�t meet criteria for maintenance Risk of overdose after tapering off

32. Methadone maintenance Single daily dose of the long-acting opioid in a controlled setting Use of methadone for >180 days (6 mo.) Counseling and social services Referral for primary medical services

33. Effectiveness Controlled trials and meta-analyses comparing medication and placebo show the superiority of agonist pharmacotherapy Improved treatment retention Reduces and often eliminates use of nonprescribed opioids Decreases criminal activity Reduces spread of HIV Results similar to long-term therapy of most chronic diseases

34. Requirements 18 years old or older Physical dependence At least 1 year of use Continuous Intermittent Withdrawal signs Chronic use Needle tracks on skin Exceptions Younger than 18 if Physical dependence Failed 2 other treatments Parental consent Not physically dependent if just released from Incarceration Hospital Pregnant

35. Blocking dose Majority of opioid receptors are blocked by methadone No withdrawal symptoms or cravings Can�t �feel� heroin effects Different for each patient Usually 60-100mg daily May be higher for some patients

36. What is the right dose? Individually determined Based on tolerance, withdrawal Other medications, physical activity level Induction Start at 30mg and rapidly titrate up to 60mg or more Stabilization Client feedback, slower titration Blind dosing Haven�t had adequate trial of MM if hasn�t been on >60mg for several months

37. Beneficial effects Enhanced recovery Reduced mortality 70% reduction Overdose Trauma Homicide Medical illnesses Improved health Medical Psychiatric Improved psychosocial functioning Employment Criminal activity Family responsibilities

38. Side effects Sedation Constipation Sweating Lower testosterone levels Arrhythmia Hyperalgesia

39. Does methadone get you high? No real euphoria Onset latency Does cause sedation Typical opioid effects Reassuring Confused with �high� Mix with other drugs benzodiazepines

40. Driving on methadone Cognitive impairment Induction Change in dose Combination with other drugs/medications Stable dose Safe to drive Complex tasks Care for others More tickets Less fear of police

41. Dispensing Dose set by physician Feedback from client Dispensed by nurse or pharmacist Liquid or tablets Specific procedure required Observed dosing Reduce diversion Take-out doses

42. Diversion of methadone Methadone is diverted to black market Has street value Dosing procedure at window to reduce diversion High security at MM clinics Most methadone sold on street is from prescriptions for pain management, not from MM clinics Methadone bought on street as bridge Can�t get anything better Trying to self-detox

43. Clinic security Alarm system Storage safe Surveillance Security guards Local police Required by DEA

44. Counseling Required component Formats Groups Individual 12-Step Relapse prevention Coping skills Case management

45. Methadone forever? No federal limit for time on methadone Some states restrict time Virginia: evaluate every 2 years to see if can come off Individual variability Time required to stabilize (use, housing, family, job) Long-term clients (decades) Initial: can�t imagine life without something Stable: able to consider coming off Taper off comfortably over months/years

46. Buprenorphine Alternative to methadone for opioid addiction treatment Long-acting opioid agonist-antagonist Multiple forms available Combined with naloxone (Suboxone): most common Buprenorphine only (Subutex) Used for treatment of acute pain (Buprenex) Detox or maintenance

47. Buprenorphine Binds to opioid receptors in body Only activates receptor around 40%, not 100% like other opioids (heroin, methadone) If already in withdrawal, 40% is pretty good If not in withdrawal, dropping from 100% to 40% receptor activation causes withdrawal Very low risk of overdose Can OD when combined with sedative (benzos)

48. Buprenorphine/naloxone Combination helps reduce abuse Naloxone only active when Suboxone is injected Results in withdrawal for users trying to get high Bup alone has similar effect when injected by those who are opioid dependent and not in withdrawal already

49. Office-based opioid therapy Buprenorphine is less restricted than methadone (Schedule III) Get prescription from pharmacy with refills (up to 6 months) Outpatient physician visits for medication checks as needed Addiction counseling is separate, patient may be referred to another provider for this service

50. Taking buprenorphine Sublingual tablet Dissolve under tongue Takes around 5 min. to dissolve Won�t be active if swallowed Comes in 2mg and 8mg tablets Typical dose is 12-16 mg once daily Can take 3 times a week

51. Methadone or Buprenorphine? Treatment efficacy equivalent Similar opioid side effects Abuse potential Slightly higher for buprenorphine in opioid non-dependent persons Buprenorphine has fewer drug interactions Methadone has no ceiling effect Buprenorphine more convenient (less restricted) Methadone less expensive Higher cost of buprenorphine, counseling separate cost Buprenorphine not age-restricted (can use in teens) Individual decision

52. Dealing with other drug use In general, all drug use is reduced on MM & bup May escalate other drug use when heroin not effective Cocaine Alcohol Sedatives (benzos) Intensify counseling, reaffirm goals for all drug abstinence

53. Monitoring for relapse Patient report Clinical observation Collateral information Family Other counselors Probation officer Urine drug screening

54. Urine drug screening Use as deterrent, not to �catch in the act� Random Minimum of 8 samples/year on maintenance therapy Verify presence of methadone, buprenorphine, etc. Look for Illicit substances Unauthorized prescriptions Opioids Benzodiazepines

55. Summary Long-term pharmacotherapy is available and effective for several addictions Medication + counseling = recovery Smoking cessation Nicotine replacement is available over-the-counter Bupropion and varenicline are available by prescription for smoking cessation Multiple medications are available by prescription for alcohol dependence

56. Summary Methadone/buprenorphine maintenance proven to reduce mortality, crime, & spread of infection Substitution therapy to eliminate withdrawal, cravings, & heroin effects Individualized dose and time on maintenance Effective for more than just opioid addiction

57. Questions?

58. Cases for Group Discussion