Transcript PPT - Larissa Mooney, M.D. - UCLA Integrated Substance Abuse

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
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Introduction to addictive disorders (SUDs)
Epidemiology
 Neurobiology
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Health effects of alcohol and opioid use
disorders
Pharmacological treatments within drug classes:
Alcohol
 Opioids
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Introduction
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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)
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12-Month and Lifetime Prevalence
Rates - NESARC
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Alcohol dependence
12 Mo: 4.3%
 Lifetime: 12% (30% for AUDs)
 Annual mortality: ~100,000
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Other (non-nicotine) drug dependence
12 Mo: 0.6%
 Lifetime: 2.7%
 Annual mortality: 17,000
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Hasin et al., 2007; Compton et al., 2007
Addiction Risk Factors
Neurobiology of Addiction
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Reward system: dopamine pathway
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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
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Treatment of withdrawal (“detox”)
Treatment of psychiatric symptoms or co-occurring
disorders
Reduction of cravings and urges
Substitution therapy
Alcohol-Related Impacts
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3rd leading cause of preventable death
15-30% of primary care and hospitalized
40% trauma patients with BAL = 0.1
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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
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Hypertension
Cardiomyopathy (enlarged heart)
Coronary heart disease (CHD), CHF
Arrhythmias
Low/moderate use: protective
Hepatic Consequences of Alcohol
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Fatty liver
Alcoholic hepatitis
Cirrhosis
Women: earlier onset of illness
Other Medical Consequences
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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
endogenous
opioids
make you
euphoric and
feel no pain
+GABA
the main
inhibitory
neurotransmitter:
slows you down
-glutamate
the main
excitatory
neurotransmitter:
speeds you up
Medications for Alcohol Dependence
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FDA-Approved:
Disulfiram (Antabuse)
 PO naltrexone (Revia)
 IM naltrexone (Vivitrol)
 Acamprosate (Campral)
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Non-FDA-approved:
Topiramate (Topamax)
 Ondansetron (Zofran)
 Quetiapine (Seroquel)
 Baclofen
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Disulfiram (Antabuse)
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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
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Disulfiram (Antabuse)
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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)
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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
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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.
Reduction in Relapse Volpicelli et al. Study*
* statistically
significant
54%
60%
Percentage
of
Participants
Who
Relapsed
During the
Study
50%
40%
23%
30%
20%
10%
0%
naltrexone group
placebo group
IM Naltrexone (Vivitrol)
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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)
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FDA Approved 2004
Dose: 666mg PO tid
Renal excretion
Structural analog of GABA
Mechanism: NMDA receptor
modulation
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Restores GABA-glutamate
balance
Blocks “negative”
reinforcement
Acamprosate (Campral)
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Start post-detox (ideal)
Side effects: diarrhea,
abdominal discomfort
Results: increased time to
relapse, increased total
abstinence, reduced drinking
days
Research on Acamprosate
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Results: In all three studies, participants treated with
acamprosate were able to maintain complete abstinence more
frequently than those treated with placebo
Complete Abstinence
40%
38%
35%
28%
30%
Percentage of
Participants 25%
Who
20%
Consumed No
Alcohol During 15%
the Entire
Study
16%
13%
13%
9%
acamprosate
placebo
10%
5%
0%
13-Week
48-Week
Study (Pelc)* Study (Sass)*
52-Week
Study
(Paille)*
* statistically
significant
Research on Acamprosate
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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.
Reduction in Drinking Days
85%
90%
80%
70%
74%
67%
67%
60%
Percentage of 50%
Days Abstinent 40%
38%
acamprosate
29%
placebo
30%
20%
10%
0%
13-Week
48-Week
Study (Pelc)* Study (Sass)*
52-Week
Study
(Paille)*
* statistically
significant
Research on Acamprosate
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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.
Regained Complete Abstinence
after First Relapse
18%
18%
16%
Percentage of
Participants
Who Regained
Complete
Abstinence for
the Reminder
of the Study
after First
Relapse
14%
12%
10%
11%
11%
8%
8%
7%
acamprosate
placebo
6%
3%
4%
2%
0%
13-Week
Study (Pelc)*
48-Week
Study
(Sass)*
52-Week
Study
(Paille)*
* statistically
significant
Public Health & Risk Behavior
Problems
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Tuberculosis
 IDUs high risk
STDs
 Gonorrhea, chlamydia, syphilis, herpes
HIV/AIDS
HBV
HCV
Opioid Dependence: NeedleRelated Problems
Abcess
 Cellulitis
 Subacute bacterial endocarditis
 Necrotizing fasciitis
 Botulism
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Treating Opioid Dependence:
Aims
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Detoxification:
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Relapse prevention:
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Opioid-based (methadone, buprenorphine)
Non-opioid based (clonidine, supportive meds)
“Rapid detox”
Agonist maintenance (methadone)
Partial agonist maintenance (buprenorphine)
Antagonist maintenance (naltrexone, Vivitrol)
Lifestyle and behavior change
Opioid Detoxification
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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
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- Other supportive meds
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anti-diarrheals, anti-emetics, ibuprofen, muscle relaxants,
BDZs
Opioid Substitution Goals
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CH3
CH2 CH N
CH3 CH2
CH3
O
Reduce symptoms & signs of withdrawal
Reduce or eliminate craving
Block effects of illicit opioids
Restore normal physiology
Promote psychosocial rehabilitation and non-drug
lifestyle
N
HO
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HO
O
O
CH3
Methadone:
Clinical Properties
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CH3
CH2 CH N
CH3 CH2
O
CH3
CH3
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
Buprenorphine for Opioid
Dependence
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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
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Sublingual administration
Subutex (Buprenorphine)
-2mg, 8mg
Suboxone (4:1 Bup:naloxone)
-2mg/0.5 mg , 8mg/2mg
Dose: 2mg-32mg/day
IM Naltrexone (Vivitrol)
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FDA approved 2010
Dose: 380 mg IM q 4 weeks
Enhanced compliance
Must be opioid-free for 7-10 days
Mechanism: opioid antagonist
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Blocks effects of opioids for 4 weeks
Challenges for Dually Diagnosed
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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
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Buckley 2006, J Clin Psychiatry; SAMHSA 2007
Traditional Treatment Models
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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
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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
Thank you!
Larissa Mooney, M.D.
UCLA Integrated Substance Abuse Programs
[email protected]