Medications For Alcohol Use Disorder

Transcription

1 Medications For Alcohol Use Disorder PRESENTED BY: Alann Weissman-Ward, MD, Addiction Medicine fellow June 19, 2018

2 DISCLOSURES Speaker: Alann Weissman-Ward, MD, has nothing to disclose. Planning Committee: The members of the planning committee (Jessica Gregg, Todd Korthuis, Melissa Weimer, John Mahan, Laura Heesacker, Kim Oveson, O Nesha Cochran, and Chris Colasurdo) have nothing to disclose. Dr. Korthuis serves as principal investigator for NIH-funded research that accepts donated extended-release naltrexone (Alkermes) and buprenorphine/naloxone (Indivior).

3 OBJECTIVES Be able to name 4 medications to treat AUD Describe contraindications and efficacy for each treatment Review which patients are appropriate for which treatment

4 PRIMARY REFERENCE SAMHSA TIP 49

5 ALCOHOL USE DISORDER MEDICATIONS 1. Oral Naltrexone 2. ER Naltrexone 3. Acamprosate 4. Disulfiram

6 ORAL NALTREXONE- 50 MG/DAY AVERAGE DOSE Approved for AUD in 1994 Metabolized by liver exclusively Still ~50% opioid blockade by 3 rd day without Marginal adherence, however can be taking prophylactically Mild effect on alcohol use, abstinence, craving

7 ORAL NALTREXONE Mechanism-competitively binds to endogenous opioid receptors and diminished pleasant sensation or high from alcohol and thought to decrease the motivational processes including reward anticipation and reinforcement

8 ORAL NALTREXONE Side effects Nausea May resemble prolonged alcohol withdrawal Rarely caused discontinuation in studies Risks Precipitated opioid withdrawal Hepatotoxicity Opioid Overdose Pregnancy category C

9 ORAL NALTREXONE Consider starting if LFTs < 5x upper limit normal AND no liver failure Urine drug screen negative for opioids 3-7 days since last drink At least 3 days since last opioid Challenge test if dependent on opioids Motivated or monitored patient Example-Patient with a history of binge drinking and wants to drink less at next outing.

10 EXTENDED RELEASE (IM) NALTREXONE AKA VIVITROL Approved 2006 Bypasses first-pass liver metabolism Improved adherence (Bryson, 2011)

11 EXTENDED RELEASE (IM) NALTREXONE Side effects Nausea (hours) Site reactions Depressed mood Risks Precipitated opioid withdrawal Pain management issues Pregnancy category C Injection technique

12 EXTENDED RELEASE (IM) NALTREXONE Consider star ting if Opioid free for 7-10 days days off buprenorphine/methadone Challenge test if dependent Comorbid OUD and AUD Trouble with adherence to daily dosing No anticipated surgery( 30 days following injection)or severe pain Example-Patient with combined opioid and alcohol use disorder motivated to not use either and needs help with intense cravings.

13 Inpatients treated with naltrexone prior to discharge All cause 30 day readmissions decreased from 23% to 8% (p=0.04) All cause ED visits decreased from 19% to 6% (p=0.05) JGIM,

14 ACAMPROSATE 666MG TID ORAL DOSE Approved in 2004-similar in structure to GABA Limited effectiveness in US trials, but effective in European Trials Renal excretion 333mg tid for CrCl 30-50mL/min avoid in CKD stage 4-5, GFR less than 30

15 ACAMPROSATE Unclear mechanism of action-thought to help modulate/normalize ETOH related brain changes Calcium vs NMDA vs glutamate Kufahl, 2014 Unclear which groups to target for research Verheul, 2005

16 ACAMPROSATE Side effects Diarrhea-dose related, transient Self-limited HA, nausea, dizziness Depression No overdose risk No meaningful interactions Pregnancy category C

17 ACAMPROSATE Effects possibly influenced/mediated by AUD severity Large placebo Timing of initiation Length of detoxification Duration of use-the longer you take it the more beneficial

18 ACAMPROSATE Consider starting if Severe liver disease without renal impairment Highly motivated Recently completed detox (5 days) Opioid dependent Other bid-tid medications Example-Patient just completed detox, motivated to not drink and is having continued post acute withdrawal symptoms, insomnia, anxiety.

19 COMBINATION NALTREXONE/ACAMPROSATE Initial study 1 : 160 patients N/A combination > A alone = N alone COMBINE 2 : 1383 patients, randomized to one of 9 interventions Slightly higher doses of N and A than typical N + counseling > placebo A = placebo PREDICT 3 : 426 patients, same format as COMBINE N = placebo; A = placebo 1:Kiefer 2003; 2: Anton, 2006; 3: Mann, 2013

20 DISULFIRAM (ANTABUSE): 250MG ONCE DAILY ORAL DOSE Approved 1951-Max dose 500 mg/day Aversive Poor adherence Can be mixed with methadone Pregnancy category C

21 DISULFIRAM: MECHANISM Blocks ALDH increased serum acetaldehyde sweating, dyspnea, vomiting, chest pain, vertigo, weakness Unpredictable severity Usually dose dependent 30 minute effect duration 2 week tail effect

22 DISULFIRAM Risks Death: rare Hepatotoxicity (1:25000) Dermatitis, acne Optic neuritis, peripheral neuritis Contraindications Severe CAD Active Psychosis Medication interactions Chlordiazepoxide, diazepam, warfarin, TCA, metronidazole

23 DISULFIRAM Consider star ting if Blood/breath alcohol 0.00 Highly motivated Directly obser ved dosing Patient requesting it No severe CAD Example-Patient has had a drink in 2 years, and is very anxious about upcoming event where there is alcohol. Wants something to take as a precautionary measure and is asking for Antabuse to take while at event.

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25 AUD TX U NDER INVESTIGATION Varenicline Gabapentin Topiramate Valproate Nalmafene Baclofen