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Alcohol Research and Health: Preventing and Treating Alcoholism and Alcohol-Related Disorders Ting-Kai Li, M.D. Director, National Institute on Alcohol Abuse and Alcoholism (NIAAA) National Institutes of Health U.S. Department of Health and Human Services September 6, 2006 Washington, D.C. - PowerPoint PPT Presentation
Citation preview
Nat
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Alc
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Alcohol Research and Health: Preventing and Treating Alcoholism and
Alcohol-Related Disorders
Ting-Kai Li, M.D.Director, National Institute on Alcohol Abuse and
Alcoholism (NIAAA)National Institutes of Health
U.S. Department of Health and Human ServicesSeptember 6, 2006Washington, D.C.
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National Institute on Alcohol Abuse and Alcoholism Mission
● increase the understanding of how alcohol use impacts normal and abnormal biological functions and behavior across the lifespan
● improve the diagnosis, prevention, and treatment of alcoholism and other alcohol-related disorders
● enhance quality health care
http://pubs.niaaa.nih.gov/publications/StrategicPlan/NIAAASTRATEGICPLAN.htm
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Extent of Alcohol-Related Health Problems in the United States
18 million Americans (8.5% of the population age 18 and older) suffer from alcohol abuse or dependence
Over 4 million of our young (18% of the population ages 12-17) report drinking monthly with more than half engaging in high-risk drinking patterns
Alcohol consumption was the third leading actual cause of death in 2000 (an estimated 85,000 deaths annually)
Alcohol problems cost U.S. society an estimated $185 billion annually
Actual Causes of Death, United States - 2000
Mokdad AH, Marks JS, Stroup DF, Gerberding JL. JAMA (2004). 29:1238-45; Mokdad AH, Marks JS, Stroup DF, Gerberding JL. (2005). JAMA 19;293:293-4. Mokdad AH, Marks JS, Stroup DF, Gerberding JL. JAMA (2004). 29:1238-45; Mokdad AH, Marks JS, Stroup DF, Gerberding JL. (2005). JAMA 19;293:293-4.
0.7%
0.8%
1.2%
1.8%
2.3%
3.1%
3.5%
15.2%
18.1%
Illicit drug use
Sexual behavior
Firearms
Motor vehicle
Toxic agents
Microbial agents
Alcohol Consumption
Poor Diet and physical inactivity
Tobacco
Actual Causes of Death are the major external (nongenetic) modifiable
factors that contribute to death in the United States
Alcohol Consumption
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Prevalence of Past-year DSM-IV Alcohol Dependence by Age United States, 2001-2002
18 + yrs. - NIAAA NESARC ( Grant, et al., (2004) Drug and Alcohol Dependence, 74:223-234)12-17 yrs - U.S. Substance Abuse and Mental Health Services Administration 2003 National Survey on
Drug Use and Health (NSDUH)
0%
2%
4%
6%
8%
10%
12%
14%
12-17 18-20 21-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69
Age
Most people seek
treatment at this ageO
ne-Y
ear P
reva
lenc
e
Prevalence of DSM-IV Alcohol Dependence in 2001-2002 was
3.8%
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Heterogeneity of Drinking Behavior: Diagnosis
Alcohol use disorders
None At-risk Harmful useDependence
(Early)At-risk Harmful useDependence
(Early)
Never exceedsdaily limits
No current symptoms (problems)
Current symptoms
• Currentsymptoms
• Withdrawal
• Severe• Relapsing• Co-morbidity
Dependence(Chronic)
8.5% of the population
*Daily limits: up to 5 (men)/4 (women)
Exceeds daily limits* with increasing frequency
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Treatment of, and Recovery from, Alcohol Dependence
Many recover, or remit, without professional interventions
Early interventions are successful in reducing chronicity and severity
Treatment success rates are 30%-60% depending on outcome measure (e.g., abstinence, heavy drinking, social functioning)
Interventions include:
Brief intervention Behavioral therapies (e.g., motivational enhancement, cognitive
behavioral, 12-steps) Pharmacological therapies
% P
PY P
opul
atio
n
0%10%20%30%40%50%60%70%80%90%
100%
<5 5 to 9 10 to 19 20+
Interval (Years)
Abstainer
Low-risk drinker
Asymptomatic riskdrinker (subclinicaldependence)
Partial Remission
Still Dependent
% P
PY P
opul
atio
n
0%10%20%30%40%50%60%70%80%90%
100%
<5 5 to 9 10 to 19 20+
Interval (Years)
Abstainer
Low-risk drinker
Asymptomatic riskdrinker (subclinicaldependence)
Partial Remission
Still Dependent0%10%20%30%40%50%60%70%80%90%
100%
<5 5 to 9 10 to 19 20+
Interval (Years)
Abstainer
Low-risk drinker
Asymptomatic riskdrinker (subclinicaldependence)
Partial Remission
Still Dependent
n=4,422Past-year Status by Interval Since Onset of Dependence
Dawson et al., (2005). Addiction. 2005 Mar;100(3):296-8. NIAAA National Epidemiological Survey on Alcohol and Related Conditions, 2001-2002
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Inherent Heterogeneity of Alcohol Dependence
Alcoholism is a common complex disease involving the interplay of genetic and environmental factors
60% genetic, both alcohol specific and non-specific
40% environment, both shared & non-shared
Gene-Environment Interactions in Alcohol Dependence
G1G1 G2G2 G3G3 G4G4 G5G5G1G1 G2G2 G3G3 G4G4 G5G5
E1E1 E2E2 E3E3 E4E4 E5E5
Alcohol Dependence
(Severe)
Alcohol Dependence
(Severe)G1G1 G2G2 G5G5
E1E1 E3E3E4E4
Alcohol Dependence
(Severe)
Alcohol Dependence
(Severe)G1G1 G2G2 G5G5
E1E1 E3E3E4E4
G2G2 G4G4
E2E2
Alcohol Dependence(Moderate)
Alcohol Dependence(Moderate)
G2G2 G4G4G2G2 G4G4
E2E2
Alcohol Dependence(Moderate)
Alcohol Dependence(Moderate)
Alcohol Dependence
(Mild)
Alcohol Dependence
(Mild)
G3G3
E2E2 E5E5
Alcohol Dependence
(Severe)
Alcohol Dependence
(Severe)G1G1 G2G2 G5G5
E1E1 E3E3E4E4
Alcohol Dependence
(Severe)
Alcohol Dependence
(Severe)G1G1 G2G2 G5G5
E1E1 E3E3E4E4
G2G2 G4G4
E2E2
Alcohol Dependence(Moderate)
Alcohol Dependence(Moderate)
G2G2 G4G4G2G2 G4G4
E2E2
Alcohol Dependence(Moderate)
Alcohol Dependence(Moderate)
Alcohol Dependence
(Mild)
Alcohol Dependence
(Mild)
G3G3
E2E2 E5E5
Genes + Environment =different types of alcoholism with different
characteristics and levels of severity
Genes + Environment =different types of alcoholism with different
characteristics and levels of severity
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Heterogeneity of Treatment Populations: Severity
Prevention
Behavioral &Medication Therapies
Diseasemanagement
Facilitated self-changeBrief counseling
None At-risk Harmful useDependence
(Early)Dependence
(Chronic)
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Heterogeneity of Treatment Populations
Co-occurring disorders
drug dependence 37xnicotine dependence 7xantisocial personality disorder 6xmood disorder (especially major
depression) 4x
anxiety disorders 3x
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Helping Patients Who Drink Too Much: A Clinician's Guide
http://www.niaaa.nih.gov
2005 Products Coming Soon● Updated medications
informationincorporating the approval of a long-acting injectable form of naltrexone and results from Project COMBINE
● Medications management support tool kit
for non-specialists prescribing medications for alcohol dependence
● Additional online supportincluding a dedicated web page for the Guide and related resources
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Medication Target Year Approved
Disulfiram Aldehyde Dehydrogenase
1949
Research from animal models over the past 25 years has provided promising targets for pharmacotherapy
Naltrexone Mu Opioid Receptor 1994
Acamprosate Glutamate and GABA-Related
2004
Naltrexone Depot Mu Opioid Receptor 2006
FDA Approved Medications for Treating Alcohol Dependence
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Multiple Neurotransmitter Systems Involved in Multiple Aspects of Alcohol Use Behavior Yield Multiple Promising
Targets
Reward Stress/Anxiety Disinhibitionopioidserotonindopaminecannabinoidglutamate
neuropeptide YCRFnociceptinnorepinephrine
GABA
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Topiramate GABA/Glutamate
Valproate GABA/Glutamate
Ondansetron 5-HT3 Receptor
Nalmefene Mu Opioid Receptor
Baclofen GABAB Receptor
Antalarmin CRF1 Receptor
Rimonabant CB1 Receptor
Medications for Treating Alcohol Dependence – Under Investigation
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Examples of NIAAA-Supported Clinical Pharmacotherapy Trials for AUDs and Co-morbid Psychiatric Conditions
Co-morbidities Medication(s)
AD/Depression naltrexone; sertraline
AD/Bipolar valproate; naltrexone
AUD/anxiety disorders venlafaxine (Effexor)
AD/schizophrenia clozapine (Clozaril)
AD/tobacco dependence bupropion (Zyban)
AD/cocaine dependence topiramate (Topamax)
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Clinical trials in the last fifteen years have shown:
Different kinds of behavioral therapies work equally well (e.g., motivational enhancement, cognitive behavioral, 12-steps)
Naltrexone with Disease Management works and potentially can be used in primary care settings
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Phases of Medications Development Supported by NIAAA And Industry
Preclinical Studies Clinical Studies
Discovery Screening Phase 1 Phase 2 Phase 3 Phase 4
Neuroscience Animal Models
Safety & dosage
Efficacy & side effects
Efficacy verification & safety
● Post-marketing effectiveness & safety
● New indications
Supported by NIAAA
Public-Private Partnership
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Personalized Medicine
Improve Disease Phenotyping risk factor identification scalable criteria and markers for severity of
diseaseImprove Understanding of Relationship of
Alcohol and Co-occurring Brain DisordersPharmacogenomics – genetic variations in
response to medications