alcohol usage

8/11/2019 Alcohol Usage

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NationalInstituteonAlcoholAbuseandAlcoholism

1

Alcohol Use, Abuse, and

Dependence

Ting-Kai Li, M.D.

Director

National Institute on Alcohol Abuse and

Alcoholism

National Institutes of Health

U.S. Department of Health and Human

Services


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http://www.niaaa.nih.gov/AboutNIAAA/DirectorsCorner/default.htm

Ting-Kai Li, M.D.Director

National Institute on Alcohol Abuse

and Alcoholism
http://www.niaaa.nih.gov/AboutNIAAA/DirectorsCorner/default.htmhttp://www.niaaa.nih.gov/AboutNIAAA/DirectorsCorner/default.htm


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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 andbehavior 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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Alcohol Use


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NationalInstituteonAl

coholAbuseandAlcoholism

Alcohol: Our Most Primitive Intoxicant

Egypt (el-Guebaly N, el-Guebaly A, 1981, I nt J Addict.,16:1207-21)

barley beer is probably the oldest drink in the world with its origin in

Egypt prior to 4200 BC

China(McGovern et al., 2004, PNAS,101:17593-17598)

7000 BC - the production of a prehistoric mixed fermented beverage ofrice, honey and fruit (neolithic village of Jiahu in Henan province)

2000 BC- unique cereal beverages (Shang and Western ZhouDynasties)


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NationalInstituteonAl

coholAbuseandAlcoholism

Ancient Warnings About Alcohol and Harmful Use

Through the Ages

1600-1050 BC- Downfall of Egyptian and ChineseEmpires and

Dynasties attributed to excessive alcohol use

460-320 BC-Grecian Scholars issued advisories on drunkenness and

moderate drinking

PlatoNo use under age 18, between 18-30 use in moderation, no

restrictions for use by those older than 40

Aristotle and Hippocrates were both critical of drunkenness

11thCentury AD - Simeon Seth, a physician in the Byzantine Court,

wrote that drinking wine to excess caused inflammation of the liver, a

condition he treated with pomegranate syrup


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Total Per Capita Consumption in Gallons of Ethanol

by State - United States, 2003

DC

1.99 or below (10)

2.00-2.24 (15)

2.25-2.49 (16)

2.50 or over (10)

DC

1.99 or below (10)

2.00-2.24 (15)

2.25-2.49 (16)

2.50 or over (10)


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Cumulative Distribution of Alcohol Consumption

in the United States

65%of thepopulation aredrinkers*

Malesreported

drinking 74%andfemales26%of allalcohol consumed

73%of the alcohol

is consumed by10%of thepopulation

* Individuals who reported drinking at least one drink in past 12-months

0

20

40

60

80

100

0 10 20 30 40 50 60 70 80 90 100

Percentile Group (High to Low)

PercentofC

onsumption

NIAAA National Epidemiological Survey on Alcohol and Related Conditions (NESARC) (2001-2002).


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Drinking Patterns: Rates and RisksModerate Drinking

Most people abstain or drink moderately

placing them at low risk for alcohol use

disorders. In general, Moderate Drinkingis upto 2drinks/dayfor men;up to 1drink/dayfor

women(USDA/HHS Dietary Guidelines, 2005)

One drink: one 12 - ounce can or bottle of

beer or wine cooler , one 5 - ounce glass of

wine , or 1.5 ounces of 80 - proof distilled

spirits .


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Nearly 3in10U.S. adultsengageinthese high-risk

drinking patterns1

Men: more than 14 drinksin a typical week

more than4 drinkson any day

Women: more than 7 drinksin a typical weekmore than 3 drinkson any day

1

Source: NIAAA National Epidemiologic Survey on Alcohol and Related Conditions,2003

Drinking Patterns: Rates and RisksHigh-Risk Drinking


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NationalInstituteonAlcoholAbuseandAlcohol

ism

Drinking Patterns: Rates and RisksBinge Drinking

The National Advisory Council on Alcohol Abuse and

Alcoholismhas recommended the following definition

of Binge Dr inking

A binge is a pattern of drinking alcohol that br ings

blood alcohol concentr ation (BAC) to 0.08 gm% or

above. For the typical adult, this pattern corresponds

to consuming 5or moredrinks (male) or 4 or more

drinks (female) in about2 hours. Binge drinking is

clearl y dangerous for the drinker and for society


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NationalInstituteonAlcoholAbuseandAlcohol

ism

U.S. Adult Drinking Patterns and Risks

2001-2002: Odds Ratios

NIAAA National Survey on Alcohol and Related Conditions, (2001-2002)

Alcohol screening limits

number of drinks:In a typical WEEK14(men), 7(women)On any DAY4(men), 3(women)

The Odds of Having An

Alcohol Use Disorder are

Increased by a Factor of. . .

Drinking Pattern

Percent of

U.S. adults

aged 18 or older

Abuse

without

dependence

Dependence

with or without

abuse

Never exceeds the weekly or dailyscreening limits

72 % Reference group(1.0)

Reference

group

(1.0)

Exceeds only the weekly limit 2 % 7.8 12.4

Exceeds only the daily limit less than

once a week14 % 17.0 33.0

Exceeds only the daily limit once a weekor more

2 % 31.1 82.0

Exceeds both weekly & daily limits once

a week or more10 % 31.1 219.4


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0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

12 13 14 15 16 17 18 19 20 21 22-23 24-25 26-29 30-34 35-49 50-64 65+

Age

Males

Females

Days

U.S. Substance Abuse and Mental Health Services Administration, 2003 National Survey on Drug Use

and Health NSDUH)

Harmful Drinking Pattern Across the LifespanNumber of Days in Past 30 Drank 5 or More Drinks

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Relative Risk of an Alcohol-Related Health

Condition as a Function of Daily Alcohol Intake

0

5

10

15

20

25

30

Oral cavity

and pharynx

Esophagus Breast Essential

hypertension

Coronary

heart disease

Ischemic

stroke

Hemorrhagic

stroke

Liver cirrhosis Chronic

pancreatitis

Condition

Relati

veRisk 50 g/day 100 g/day

Adapted from Corrao et al. (2004), Preventi ve Medicine, 38:613619

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Disorder Odds

Anxiety Disorders 2.6x

Mood Disorders (especially Major Depression) 4.1x

Personality Disorders 4.0x

Antisocial Personality Disorder 7.1x

Drug Dependence 36.9x

Nicotine Dependence 6.4x

NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2004.

Odds of Co-Occurrence of Current (12-month)

DSM-IV Alcohol Dependence and Selected Psychiatric

Conditions

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Burden of Disease Attributable to Alcohol Among the 10

Leading Risk Factors for Disease In Developed Countries

0% 2% 4% 6% 8% 10% 12% 14%

Iron deficiency

Unsafe sex

Illicit drugs

Physical inactivity

Low fruit and vegetable intake

Overweight

Cholesterol

Alcohol

Blood pressure

Tobacco

% Total Number of Health Years Lost to Death/Disability

The World Health Report 2002: http://www.who.int/whr/2002/en/whr2002_annex14_16.pdf

NationalI

nstituteonAlcohol

AbuseandAlcoho

lism

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Alcohol Abuse

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DSM-IV Alcohol Abuse ICD-10 Harmful Use

A. A maladaptive pattern of alcohol use leading toclinically significant impairment or distress, asmanifested by one or moreof the following occurringwithin a 12-month period:

A. A pattern of alcohol use that iscausing physical and/or mentaldamage to health.

recurrent drinking resulting in a failure to fulfillmajor role obligations

recurrent drinking in physically hazardoussituations*

recurrent alcohol-related legal problems

continued use despite having persistent or

recurrent alcohol-related social or interpersonalproblems

B. The symptoms have never met thecriteria for alcoholdependence B. No concurrent diagnosis of thealcohol dependence syndrome

Definition and Diagnostic Criteria for Alcohol Abuse/Harmful Use of Alcohol

*Ninety percent of those diagnosed as having Alcohol Abuse endorse this criterion.

Others are 20% or less (Dawson, DA. Unpublished NESARC Analysis, 2006)

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Do Alcohol Use Disorders Fall Along a Continuum

of Severity?

Data from NIAAAstwo general population sampleepidemiologicalstudies* and others (e.g., Langenbucher et al., 2004; Krueger et al.,2004; Kahler and Strong, 2006; Saha et al., 2006; Proudfoot et al.,2006) agree that:

Alcohol Use Disorders are not bi-axial (abuse and dependence), butfall along a continuum of severity

Current criteria for alcohol abuse are not associated only with amilder form of alcohol use disorder; most tap into the more severeend of an alcohol use continuum

Current criteria for abuse and dependence contain redundancies

* NESARCand the 1991-1992 NIAAA National Longitudinal Alcohol Epidemiological

Survey (NLAES)

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Alcohol Dependence

(Alcoholism)

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Elements of Alcohol Dependence: DSM-IV and ICD-10(3of 7during one year required for diagnosis)

* elements of addiction

1. Tolerance

2. Withdrawal:

relief/avoidance

Pharmacological

3. Impaired control*

Maladaptive

larger/longer

unsuccessful attempts toquit/control

4. Compulsive Use*

craving (ICD-10) only)

neglect activities

time spent

use despite negative

consequences

Severity of Addiction

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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 onDrug 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 ageOne-YearPrevalence

Prevalence of

DSM-IV Alcohol

Dependence in

2001-2002 was

3.8%

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Etiology of Alcohol Use Disorders

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Alcohol use, abuse, and dependencearecomplex behavioral traits influenced by many

factors:

geneticandbiologicalresponses

environmentalinfluences

stages of development, from childhood to early

adulthood

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Alcoholism: A Common Complex

Disease


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NationalInstituteonA

lcoholAbuseandAlcoholism

Pharmacokinetics: absorption, distribution, andmetabolism of alcohol

3-4 fold

Pharmacodynamics: subjective and objectiveresponses to alcohol

2-3 fold

About one-half of these differences

is genetic

Between Individual Variations in Responses to

Alcohol

(Why drink; Drink more; Drink despite)

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Metabolism of Ethanol and Acetaldehyde in

Hepatocyte

TCATCA

ATP

CO2

H2O

NAD+

NADH

NAD+

NADH

NAD+

NADH

NAD+

NADH

electrontransportelectrontransport

Energy Yield: 7 Kcals/g

CH3CH2OH(mM)

ADHADH

CH3CHO(M)

NAD+ NADHNAD+ NADH

ALDH1ALDH1

CH3CHOALDH2ALDH2

CH3COOH(mM)

CH3COOH

CH3

COOH(mM)

CYTOSOL

NADHShuttle

NAD+ NADH

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Age at Onset: DSM-IV Age of First Use of Alcohol,

Nicotine, and Cannabis

0%

5%

10%

15%

20%

25%

30%

35%

5 10 15 20 25 30 35 40 45 50

Age

Age of First Alcohol Use

Age at first Nicotine Use

Age of First Cannabis Use

Perc

entageineacha

gegroupwho

beginusinga

lcohol

0%

5%

10%

15%

20%

25%

30%

35%

5 10 15 20 25 30 35 40 45 50

Age

Age of First Alcohol Use

Age at first Nicotine Use

Age of First Cannabis Use

Perc

entageineacha

gegroupwho

beginusinga

lcohol

Source: NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003

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2001-2002

0

10

20

30

40

50

60

=21

Age at First Use of Alcohol

%Prevalence

Source: 2001-2002 National Epidemiologic Survey on Alcohol nad Related

Conditions; Laboratory of Epidemiology and Biometry; DICBR, NIAAA,

Bethesda, MD.

1991-1992

0

10

20

30

40

50

60

13 14 15 16 17 18 19 20 21

Age at First Use of Alcohol

%P

revale

nc

Source: Grant and Dawson. (1988). J. Substance Abuse, 10(2):163-73

Prevalence of Lifetime Alcohol Dependence by Age of

First Alcohol Use and Family History of Alcoholism

Parental History Positive

Total

Parental History Negative

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Dail Cons mption b P and NP Rats Responding on a T o


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lcoholAbuseandAlcoho

lism

Daily Consumption by P and NP Rats Responding on a Two-

Bar Operant Task for Water and Different Concentrations of

Ethanol

% ethanol

Water

(ml/day)

E

thanol

(ml/day)

g/kg/day

2 5 10 15 20 25 4030

*p=


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lism

Treatment of Alcohol Use Disorders

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lism Many recover, or remit,

without professionalinterventions

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

PYPopulation

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%


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lism

Heterogeneity of Treatment Populations: Severity

* >4 drinks/day, 14 drinks/week (men)

>3 drinks/day, 7 drinks/week (women)

Disease

management

None Harmful useDependence

(Early)Dependence

(Chronic)At-risk*

Prevention Facilitated self-changeBrief counseling

Behavioral and MedicationTherapy

* >4 drinks/day, 14 drinks/week (men)

>3 drinks/day, 7 drinks/week (women)

Disease

management

Disease

management

None Harmful useDependence

(Early)Dependence

(Chronic)At-risk*

Prevention Facilitated self-changeBrief counseling

Behavioral and MedicationTherapy

Screening

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lism

Clinical Trials in the Last Fifteen Years Have

Shown:

Different kinds of behavioral therapies work equally

well (e.g., motivational enhancement, cognitivebehavioral, 12-steps)

Naltrexone with Disease Management works and

potentially can be used in primary care settings


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lism

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 ApprovedMedications for Treating AlcoholDependence

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Medication Target

Topiramate GABA/Glutamate

Valproate GABA/Glutamate

Ondansetron 5-HT3Receptor

Nalmefene Mu Opioid Receptor

Baclofen GABABReceptor

Antalarmin CRF1 Receptor

Rimonabant CB1 Receptor

Medications for Treating Alcohol Dependence

Under Investigation

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lism

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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NIAAA Clinicians Guide


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NIAAA Clinicians GuideHelping Patients Who Drink Too Much

Based on the AUDIT-C:

1. How often do you have a drinkcontaining alcohol?

2. How many drinks containing alcohol doyou have on a typical day when you are

drinking?

3. How often do you have 6 or more drinkson an occasion?

Thethird question aloneis:

sensitive for heavy drinking (79%)and alcohol abuse/ dependence

(81%)

specific(83%)for heavy drinking, abuse and dependence1

1Bush et al, Arch Intern Med. 1998;158:1789-1795

Information and training materials for the NIAAA Clinicians guide are available at:

http://pubs.niaaa.nih.gov/publications/practitioner/CliniciansGuide2005/Guide_Slideshow.htm

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C l i Al h l R h S h d


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Conclusion: Alcohol Research Strengths and

Opportunities

Alcohol pharmacogenetics

human and animal models

Animal models

genes, pathways and networks, and GxEinteractions

Epidemiology

longitudinal general population and high-risk

studies

Treatment

behavioral

alcohol usage

Documents