Alcohol Research and Health: Preventing and Treating Alcoholism and Alcohol-Related Disorders

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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

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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

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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


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


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


E1E1 E3E3E4E4

G2G2 G4G4

E2E2

Alcohol Dependence(Moderate)


G2G2 G4G4G2G2 G4G4

E2E2



Alcohol Dependence

(Mild)

Alcohol Dependence

(Mild)

G3G3

E2E2 E5E5

Alcohol Dependence

(Severe)

Alcohol Dependence


E1E1 E3E3E4E4

Alcohol Dependence

(Severe)

Alcohol Dependence


E1E1 E3E3E4E4

G2G2 G4G4

E2E2



G2G2 G4G4G2G2 G4G4

E2E2



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

Alcohol Research and Health: Preventing and Treating Alcoholism and Alcohol-Related Disorders

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Transcript of Alcohol Research and Health: Preventing and Treating Alcoholism and Alcohol-Related Disorders