Medication Assisted Treatment for Alcohol
and Opioid Dependence
Larissa Mooney, M.D.Assistant Professor of Psychiatry
UCLA Integrated Substance Abuse Programs
April 25, 2012
Objectives Introduction to addictive disorders
(SUDs) Epidemiology Neurobiology
Health effects of alcohol and opioid use disorders
Pharmacological treatments within drug classes: Alcohol Opioids
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)
12-Month and Lifetime Prevalence
Rates - 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
Addiction Risk Factors
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
Reward pathway -- mesolimbic dopamine system
Pharmacotherapy in Substance Use Disorders
Treatment of withdrawal (“detox”) Treatment of psychiatric symptoms or
co-occurring disorders Reduction of cravings and urges Substitution therapy
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
Cardiovascular Consequences of Alcohol
Hypertension Cardiomyopathy (enlarged heart) Coronary heart disease (CHD), CHF Arrhythmias Low/moderate use: protective
Hepatic Consequences of Alcohol
Fatty liver Alcoholic hepatitis Cirrhosis Women: earlier onset of illness
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
Alcohol Effects: Neurotransmitters
dopamine
makes you
happy
-glutamate the main excitatory
neurotransmitter: speeds
you up
+GABA the main inhibitory
neurotransmitter:slows you down
endogenous
opioids make you euphoric and feel no pain
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
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
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
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
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.
23%
54%
0%
10%
20%
30%
40%
50%
60%
Percentage of
Participants Who
Relapsed During the
Study
naltrexone group placebo group
Reduction in Relapse - Volpicelli et al. Study*
* statistically significant
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
Acamprosate (Campral) 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) Start post-detox
(ideal) Side effects:
diarrhea, abdominal discomfort
Results: increased time to relapse, increased total abstinence, reduced drinking days
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
38%
13%
28%
13%16%
9%
0%
5%
10%
15%
20%
25%
30%
35%
40%
Percentage of Participants
Who Consumed No Alcohol During
the Entire
13-WeekStudy (Pelc)*
48-WeekStudy (Sass)*
52-WeekStudy
(Paille)*
Complete Abstinence
acamprosateplacebo
* statistically significant
Study
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.
67%
29%
74%
38%
85%
67%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
Percentage of Days Abstinent
13-WeekStudy (Pelc)*
48-WeekStudy (Sass)*
52-WeekStudy
(Paille)*
Reduction in Drinking Days
acamprosateplacebo
* statistically significant
Research on Acamprosate
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.
11%
8%
18%
7%
11%
3%
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
Percentage of Participants
Who Regained Complete
Abstinence for the Reminder of the Study after First
13-WeekStudy (Pelc)*
48-WeekStudy
(Sass)*
52-WeekStudy
(Paille)*
Regained Complete Abstinence after First Relapse
acamprosateplacebo
* statistically significant
Relapse
Research on Acamprosate
Public Health & Risk Behavior Problems
Tuberculosis IDUs high risk
STDs Gonorrhea, chlamydia, syphilis,
herpes HIV/AIDS HBV HCV
Opioid Dependence: Needle-Related Problems
Abcess Cellulitis Subacute bacterial
endocarditis Necrotizing fasciitis Botulism
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
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
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
OOH O
N
OH
CH3 CH2 CH2 CH N
CH3CH3
CH3
O
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
CH3 CH2 CH2 CH N
CH3CH3
CH3
O
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
Buprenorphine Formulations
Sublingual administration Subutex (Buprenorphine)
-2mg, 8mg Suboxone (4:1 Bup:naloxone)
-2mg/0.5 mg , 8mg/2mg Dose: 2mg-32mg/day
IM Naltrexone (Vivitrol) FDA approved 2010 Dose: 380 mg IM q 4 weeks Enhanced compliance Must be opioid-free for 7-10 days Mechanism: opioid antagonist
Blocks effects of opioids for 4 weeks
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
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
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
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