Medication and Behavioral Treatment of Substance Use Disorders

Transcription

1 Medication and Behavioral Treatment of Substance Use Disorders Brian Fuehrlein, MD, PhD Director, Psychiatric Emergency Room, VA Connecticut and Assistant Professor of Psychiatry, Yale University 1

2 Brian Fuehrlein, Disclosures I have no financial relationships to disclose. The contents of this activity may include discussion of off label or investigative drug uses. The faculty is aware that is their responsibility to disclose this information. 2

3 Planning Committee, Disclosures AAAP aims to provide educational information that is balanced, independent, objective and free of bias and based on evidence. In order to resolve any identified Conflicts of Interest, disclosure information from all planners, faculty and anyone in the position to control content is provided during the planning process to ensure resolution of any identified conflicts. This disclosure information is listed below: The following developers and planning committee members have reported that they have no commercial relationships relevant to the content of this module to disclose: PCSS-MAT lead contributors Frances Levin, MD and Adam Bisaga, MD; AAAP CME/CPD Committee Members Dean Krahn, MD, Kevin Sevarino, MD, PhD, Tim Fong, MD, Tom Kosten, MD, Joji Suzuki, MD; and AAAP Staff Kathryn Cates-Wessel, Miriam Giles, Carol Johnson and Justina Pereira. All faculty have been advised that any recommendations involving clinical medicine must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported, or used in the presentation must conform to the generally accepted standards of experimental design, data collection, and analysis. The content of this CME activity has been reviewed and the committee determined the presentation is balanced, independent, and free of any commercial bias. Speakers will inform the learners if their presentation will include discussion of unlabeled/investigational use of commercial products. 3

4 Target Audience The overarching goal of PCSS-MAT is to make available the most effective medication-assisted treatments to serve patients in a variety of settings, including primary care, psychiatric care, and pain management settings. 4

5 Educational Objectives At the conclusion of this activity participants should be able to: Identify the primary medications in the treatment of alcohol use disorder Define the primary medications in the treatment of opioid use disorder Describe the primary options for psychosocial treatment and support 5

6 Review Substance use disorder is a chronic relapsing and remitting illness A multimodal approach of medications and psychosocial treatment and support is considered the most effective for opioid and alcohol use disorder Withdrawal management is not treatment 6

7 Case Presentation #1 Bob is a 50-year-old male with chronic alcohol use disorder. Recently completed court-ordered detox then 30-day residential treatment Relapsed upon discharge from treatment due to cravings Ambivalent about sobriety Lives alone Diagnosed with cirrhosis and coronary artery disease Has been prescribed low dose opioids for chronic back pain 7

8 Case Presentation #2 Steve is a 27-year-old man diagnosed with alcohol use disorder Recently completed a 90-day treatment program and remains sober, but struggles with cravings 2-3 times per week Generally prefers not taking medications but is willing to try Committed to recovery, attends daily AA meetings No medical problems Lives with a supportive family 8

9 Case Presentation #3 Denise is a 40-year-old woman with alcohol use use disorder Recently arrested for 3 rd DUI Currently in court-ordered intensive outpatient program Denies cravings Highly motivated by legal pressures Inquired about a medication that will prevent her from drinking Lives with husband who is willing to do whatever it takes to help her No medical problems 9

10 Alcohol Use Disorder 10

11 Disulfiram (Antabuse) Approved in 1957 for alcohol use disorder Aversive therapy, does not reduce cravings Inhibits aldehyde dehydrogenase 11

12 Disulfiram (Antabuse) Increasing levels of acetaldehyde causes an aversive reaction Leads to tachycardia, flushing, nausea, vomiting, hypotension Within hours of first dose and days to weeks after last dose Must fully educate patients about these risks Most effective with motivated patients Most effective with supervised administration 12

13 Disulfiram (Antabuse) Starting and maintenance dose mg daily Metabolized through liver and LFTs should be checked and monitored Patients should be alcohol free for >12 hours Occasional aversive reactions from hidden alcohol sources are possible Must educate patient about the possibility of a severe reaction with alcohol consumption Severe myocardial disease, coronary occlusion and severe liver disease are contraindications while psychosis is a relative contraindication 13

14 Naltrexone Orally available mu opioid receptor antagonist, not to be confused with naloxone Alcohol causes endogenous opioid release and reinforcing effects Naltrexone reduces cravings and the positive reinforcing effects of alcohol Naltrexone reduces amount consumed when drinking 14

15 Naltrexone Orally once daily starting and maintenance dose is 25-50mg Patients must be opioid free for >7 days for standard opioids and days for long acting opioids like methadone Obtain baseline liver function tests including AST, ALT, and total bilirubin prior to instituting naltrexone (oral or injectable) therapy. Only initiate therapy if liver function tests (LFTS) are lower than 5x the upper limit of normal (ULN). Obtain follow-up AST and ALT levels approximately 8-12 weeks after initiation of naltrexone with quarterly monitoring thereafter Side effects are generally mild and include nausea, headache, dizziness, fatigue and insomnia Hepatotoxicity is a black box warning though is rare 15

16 Extended Release Naltrexone (Vivitrol TM ) Once-a-month and injectable into gluteal muscle Injection site reactions are a possible side effect Consider a trial of oral naltrexone Avoids first-pass metabolism hence total dose is lower (380mg) Patients should not be prescribed opioids and this should be confirmed with a urine drug screen or naloxone challenge Patients had longer time of sobriety and fewer drinking days per month Particularly effective following at least 4 days of abstinence, though may also be used in those actively drinking 16

17 Acamprosate (Campral TM ) NMDA receptor modulator and GABA/glutamate stabilization May also stabilize the hypothalamic pituitary axis These actions offer neuroprotection and reduce the post-acute withdrawal symptoms of anxiety and irritability, which may contribute to a relapse 17

18 Acamprosate (Campral TM ) Reduces the risk of return to drinking Increases the duration of abstinence Likely as effective as naltrexone Well tolerated and not metabolized through the liver Gastro-intestinal side effects are most common Therapeutic dose is 666mg TID (6 pills per day) Adherence is the primary problem 18

19 Topiramate (Topamax R ) Off-label use for alcohol use disorder to reduce post-acute withdrawal symptoms and craving Facilitates GABA and antagonized glutamate and may decrease dopamine activity in the reward pathway and reduce withdrawal symptoms Has shown efficacy in doses mg daily and is better tolerated if titrated slowly Compared to placebo, reduced drinks per day, number of heavy drinking days and days of abstinence Primary side effect is cognitive slowing 19

20 Gabapentin (Neurontin R ) Indicated for seizure disorder, restless leg syndrome and postherpetic pain Off-label use for alcohol use disorder (among other things) GABA receptor agonist Very mild side effect profile and very well tolerated Dosed up to 1200 mg TID Results are promising 20

21 Medication Assisted Treatment for Opioid Use Disorder 21

22 Methadone What does methadone have to do with this? 22

23 Methadone 23

24 Methadone Pharmacology Full mu opioid receptor agonist Half life hours Increased risk of respiratory depression and overdose when mixed with alcohol and/or benzodiazepines Very effective at doses >80-140mg once daily 24

25 Methadone Mechanism of Action Being a full agonist with a long half-life, methadone suppresses signs and symptoms of opioid withdrawal by reaching a steady-state level with once daily dosing It eliminates opioid cravings May also serve to block the reinforcing effects of illicit opioids CASAColumbia. (2012). Addiction medicine: Closing the gap between science and practice. 25

26 Methadone Delivery For treatment of OUD, methadone must be administered in a federally regulated opioid treatment program Patients are seen daily for administered dosing with gradually increasing take home privileges on symptom improvement Once per week visits is the least restrictive 26

27 Methadone Side Effects Respiratory depression, particularly with benzos or alcohol Prolonged QTc at doses >100mg, if seen daily Weight gain Constipation Decreased testosterone Dry mouth Urinary retention 27

28 Buprenorphine DATA 2000 permitted scheduled III-V medications to treat opioid use disorder in an office-based setting Buprenorphine is schedule III Synthetic opioid that functions as a partial agonist at the mu opioid receptor Partial agonist effect serves to reduce cravings and eliminate withdrawal Unlike full agonists, partial agonists create a ceiling effect at higher doses thus no increased respiratory depression or euphoria at higher doses 28

29 Buprenorphine Pharmacology Compared to methadone, buprenorphine has a reduced overdose potential and improved safety profile Partial agonist may precipitate withdrawal if taken by someone who is taking daily doses of a full agonist need to be in mild withdrawal before taking first dose Buprenorphine has a high affinity to the mu receptor and results in blocking other opioids This may result in precipitated withdrawal This blocks other full agonist misuse Formulated with naloxone (4:1 ratio) to reduce misuse and diversion naloxone is not bioavailable unless injected Available in tablets, films, and long-acting implant Buprenorphine is as effective as methadone except for treatment retention 29

30 Extended-Release Naltrexone Opioid antagonist Provides complete blockade of the mu opioid receptors (though may be overridden in emergency situations for acute pain control) Counterintuitively, may actually reduce cravings for opioids (different mechanism than methadone/buprenorphine) Studies are underway to determine efficacy compared to buprenorphine and methadone Daily oral naltrexone is generally not recommended for OUD given problems with medication adherence 30

31 Pharmacotherapy for Opioid Use Disorder % Mu Receptor Intrinsic Activity Full Agonist: Methadone Partial Agonist: Buprenorphine Antagonist: Naltrexone 0 no drug low dose high dose Drug Dose 31

32 Behavioral Treatment and Psychosocial Supports for SUDs 32

33 Evidence-Based Therapy Evidence-based therapy should be used in conjunction with medications when possible. For substances without an approved medication, evidence-based therapy can be one of the primary means of sobriety. Evidence-based therapies include CBT 1, CRAFT 2 and CM 3 33

34 Cognitive Behavioral Therapy In maladaptive behavioral patterns, learning plays a critical role Teach patients to identify and correct problematic behaviors by applying learned skills Anticipating problems and enhancing self control by developing coping strategies Exploring consequences, self monitoring for cravings early and identifying risky situations 34

35 CRAFT Community Reinforcement and Family Training Increase family compliance with an intervention to increase the rate of treatment for the patient Motivation building, functional analysis, communication skill training, life enrichment and other skills Targets the family of those with substance use disorders Has been shown to improve engagement in treatment 35

36 Contingency Management Highly effective in increasing treatment retention and promoting abstinence Provides tangible rewards to reinforce positive behaviors, such as abstinence Voucher based reinforcement involves vouchers that are exchanged for goods and services Vouchers increase in value with more negative urine drug screens Prize incentives provide chances to win cash prizes Each negative urine is a chance to win 36

37 Psychosocial Recovery Supports Psychosocial recovery supports, while not evidencebased therapies, are potentially very important and very helpful. When medications and other evidence-based therapies are not available, psychosocial supports may be all that is available The primary psychosocial supports include Alcoholics Anonymous, SMART Recovery and supportive psychotherapy 37

38 Alcoholics Anonymous Founded in 1935 Primary purpose is to stay sober and help other alcoholics achieve sobriety The only requirement for AA membership is a desire to stop drinking No cost, no side effects, readily available and may greatly benefit the patient Nearly all patients with a substance use disorder will be familiar with AA, their providers should be too AA is the primary psychosocial support available Tonigan, S., et al. Participation and involvement in Alcoholics Anonymous,

39 Alcoholics Anonymous The recovery program Meetings (90 in 90) Sponsorship Step work Commitments 39

40 Alcoholics Anonymous Meetings 90 meetings in 90 days is the minimum recommended starting point Meetings are widely available, often have themes and many attend daily meetings indefinitely Sponsorship A sponsor is one person to turn to without embarrassment when doubts, questions or problems linked to alcoholism arise 40

41 Alcoholics Anonymous Step work Step 1: We admitted we were powerless over alcohol and our lives had become unmanageable There are twelve steps that should be worked through as part of the recovery program Commitments Commitment can be small, i.e., will make coffee at a particular meeting, or large, i.e., becoming a sponsor This shows responsibility to something or someone other than self 41

42 SMART Recovery Self Management And Recovery Training Alternative or supplement to AA Non confrontational motivational, behavioral and cognitive methods Meetings are integral to the program SMART recovery relies less on religion and spirituality Four point program Building motivation Coping with urges Problem solving Lifestyle balance Horvath, T. and Yeterian, J. SMART Recovery: Self-Empowering, Science-Based Addiction Recovery Support. Journal of Groups in Addiction Recovery, 7: ,

43 Supportive Recovery Psychotherapy The primary goal is to strengthen the ability to cope with stressors Close, empathetic listening Reinforcing and strengthening resilience Building and maintaining self-esteem Encourage sharing of feelings and thoughts 43

44 Summary Medications are an integral part of substance use disorder treatment Only a handful of medications are currently approved, with others under investigation Psychosocial supports may be used in conjunction with medications and may be particularly important when medications or behavioral treatments are not available 44

45 References Fuehrlein and Gold. Medication assisted recovery in alcohol and opioid dependence. Directions in Psychiatry. 33(2):15-29, 2013 Horvath, T. and Yeterian, J. SMART Recovery: Self-Empowering, Science-Based Addiction Recovery Support. Journal of Groups in Addiction Recovery, 7: , 2012 Meyers, R. and Smith, J. Clinical Guide to Alcohol Treatment: The Community Reinforcement Approach. Guildford Press, 1995 Newman, C. Cognitive Therapy of Substance Abuse. The Guildford Press, 1993 Tonigan, S., et al. Participation and involvement in Alcoholics Anonymous, 2003 Prendergast, M., et al. Contingency management for treatment of substance use disorders: a meta-analysis. Addiction, 101(11): ,

46 PCSS-MAT Mentoring Program PCSS-MAT Mentor Program is designed to offer general information to clinicians about evidence-based clinical practices in prescribing medications for opioid addiction. PCSS-MAT Mentors are a national network of providers with expertise in addictions, pain, evidence-based treatment including medicationassisted treatment. 3-tiered approach allows every mentor/mentee relationship to be unique and catered to the specific needs of the mentee. No cost. For more information visit: pcssmat.org/mentoring 46

47 PCSS Discussion Forum Have a clinical question? 47

48 PCSS-MAT is a collaborative effort led by the American Academy of Addiction Psychiatry (AAAP) in partnership with the: Addiction Technology Transfer Center (ATTC); American Academy of Family Physicians (AAFP); American Academy of Pain Medicine (AAPM); American Academy of Pediatrics (AAP); American College of Emergency Physicians (ACEP); American College of Physicians (ACP); American Dental Association (ADA); American Medical Association (AMA); American Osteopathic Academy of Addiction Medicine (AOAAM); American Psychiatric Association (APA); American Psychiatric Nurses Association (APNA); American Society of Addiction Medicine (ASAM); American Society for Pain Management Nursing (ASPMN); Association for Medical Education and Research in Substance Abuse (AMERSA); International Nurses Society on Addictions (IntNSA); National Association of Community Health Centers (NACHC); and the National Association of Drug Court Professionals (NADCP). For more information: Funding for this initiative was made possible (in part) by grant no. 1U79TI from SAMHSA. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government. 48

49 PCSS-MAT: Training, Mentoring, Resources 49