Alcohol Use, Abuse, and Dependence



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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
  • http://www.niaaa.nih.gov/AboutNIAAA/DirectorsCorner/default.htm
  • Ting-Kai Li, M.D.
  • Director
  • National Institute on Alcohol Abuse
  • and Alcoholism

National Institute on Alcohol Abuse and Alcoholism Mission

Alcohol Use

Alcohol: Our Most Primitive Intoxicant

  • Egypt (el-Guebaly N, el-Guebaly A, 1981, Int 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 of rice, honey and fruit (neolithic village of Jiahu in Henan province)
    • 2000 BC- unique cereal beverages (Shang and Western Zhou Dynasties)

Ancient Warnings About Alcohol and Harmful Use Through the Ages

  • 1600-1050 BC - Downfall of Egyptian and Chinese Empires and Dynasties attributed to excessive alcohol use
  • 460-320 BC- Grecian Scholars issued advisories on drunkenness and moderate drinking
    • Plato – No 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
  • 11th Century 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

Total Per Capita Consumption in Gallons of Ethanol by State - United States, 2003

Cumulative Distribution of Alcohol Consumption in the United States

  • NIAAA National Epidemiological Survey on Alcohol and Related Conditions (NESARC) (2001-2002).
  • Drinking Patterns: Rates and Risks Moderate Drinking
  • Most people abstain or drink moderately placing them at low risk for alcohol use disorders. In general, Moderate Drinking is up to 2 drinks/day for men; up to 1 drink/day for 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
  • .

Drinking Patterns: Rates and Risks High-Risk Drinking

  • Nearly 3 in 10 U.S. adults engage in these high-risk drinking patterns1
  • Men: more than 14 drinks in a typical week
    • more than 4 drinks on any day
    • Women: more than 7 drinks in a typical week
    • more than 3 drinks on any day
  • 1 Source: NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003

Drinking Patterns: Rates and Risks Binge Drinking

  • The National Advisory Council on Alcohol Abuse and Alcoholism has recommended the following definition of Binge Drinking
    • A “binge” is a pattern of drinking alcohol that brings blood alcohol concentration (BAC) to 0.08 gm% or above. For the typical adult, this pattern corresponds to consuming 5 or more drinks (male) or 4 or more drinks (female) in about 2 hours. Binge drinking is clearly dangerous for the drinker and for society

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 WEEK—14 (men), 7 (women) On any DAY— 4 (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 daily screening 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 week
  • 14 %
  • 17.0
  • 33.0
  • Exceeds only the daily limit once a week or more
  • 2 %
  • 31.1
  • 82.0
  • 10 %
  • 31.1
  • 219.4

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

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

Relative Risk of an Alcohol-Related Health Condition as a Function of Daily Alcohol Intake

  • Adapted from Corrao et al. (2004), Preventive Medicine, 38:613–619

Odds of Co-Occurrence of Current (12-month) DSM-IV Alcohol Dependence and Selected Psychiatric Conditions

  • 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.

Burden of Disease Attributable to Alcohol Among the 10 Leading Risk Factors for Disease In Developed Countries

  • The World Health Report 2002: http://www.who.int/whr/2002/en/whr2002_annex14_16.pdf
  • National Institute on Alcohol Abuse and Alcoholism

Alcohol Abuse

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

  • DSM-IV Alcohol Abuse
  • A. A maladaptive pattern of alcohol use leading to clinically significant impairment or distress, as manifested by one or more of the following occurring within a 12-month period:
  • A. A pattern of alcohol use that is causing physical and/or mental damage to health.
  • recurrent drinking resulting in a failure to fulfill major role obligations
  • recurrent drinking in physically hazardous situations*
  • recurrent alcohol-related legal problems
  • continued use despite having persistent or recurrent alcohol-related social or interpersonal problems
  • B. The symptoms have never met the criteria for alcohol dependence
  • B. No concurrent diagnosis of the alcohol dependence syndrome
  • *Ninety percent of those diagnosed as having Alcohol Abuse endorse this criterion. Others are 20% or less (Dawson, DA. Unpublished NESARC Analysis, 2006)

Do Alcohol Use Disorders Fall Along a Continuum of Severity?

  • Data from NIAAA’s two general population sample epidemiological studies* 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), but fall along a continuum of severity
    • Current criteria for alcohol abuse are not associated only with a milder form of alcohol use disorder; most tap into the more severe end of an alcohol use continuum
    • Current criteria for abuse and dependence contain redundancies
  • * NESARC and the 1991-1992 NIAAA National Longitudinal Alcohol Epidemiological Survey (NLAES)

Alcohol Dependence (Alcoholism)

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

  • * elements of addiction
  • 1. Tolerance
  • 2. Withdrawal: relief/avoidance
  • Pharmacological
  • 3. Impaired control*
  • Maladaptive
  • larger/longer
  • unsuccessful attempts to quit/control
  • 4. Compulsive Use*
  • craving (ICD-10) only)
  • Severity of Addiction

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)
  • Prevalence of DSM-IV Alcohol Dependence in 2001-2002 was 3.8%

Etiology of Alcohol Use Disorders

  • Alcohol use, abuse, and dependence are complex behavioral traits influenced by many factors:
    • genetic and biological responses
    • environmental influences
    • stages of development, from childhood to early adulthood
  • Alcoholism: A Common Complex Disease

Developmental Trajectory of AUD Initiation and Continuation of Drinking

  • Extent of Influence
  • Initiation of Drinking
  • Progression
  • Alcoholic Drinking
  • Environmental (familial and non familial)
  • Personality/Temperament (Endophenotype)
  • Pharmacological effects of ethanol (Intermediate Phenotypes)

Gene-Environment Interactions in Alcohol Dependence

Between Individual Variations in Responses to Alcohol (Why drink; Drink more; Drink despite)

  • Pharmacokinetics: absorption, distribution, and metabolism of alcohol
  • 3-4 fold
  • Pharmacodynamics: subjective and objective responses to alcohol
  • 2-3 fold
  • About one-half of these differences is genetic

Metabolism of Ethanol and Acetaldehyde in Hepatocyte

  • Age at Onset: DSM-IV Age of First Use of Alcohol, Nicotine, and Cannabis
  • Source: NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003

Prevalence of Lifetime Alcohol Dependence by Age of First Alcohol Use and Family History of Alcoholism

  • Parental History Positive
  • Total
  • Parental History Negative

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)
  • Ethanol
  • ( ml/day) g/kg/day
  • 2
  • 5
  • 10
  • 15
  • 20
  • 25
  • 40
  • 30
  • *p=<0.05
  • Murphy JM, Gatto GJ, McBride WJ, Lumeng L, Li TK ((1989). Alcohol. 6(2):127-31.

Treatment of Alcohol Use Disorders

Treatment of, and Recovery from, Alcohol Dependence

Heterogeneity of Treatment Populations: Severity

Clinical Trials in the Last Fifteen Years Have Shown:

  • 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

Behavioral Therapies

  • Treatment Intervention
  • Primary Target Population(s)
  • High-risk drinkers
  • Alcohol abusers
  • Alcohol- dependent
  • Brief intervention
  • Motivational enhancement therapy
  • Cognitive behavioral therapy
  • Couples (marital) and family therapies
  • Community reinforcement
  • Selected References: Moyer et al. (2002) Addiction, 97: 279-292; Miller et al. (2002) Addiction, 97: 265-277; O’Farrell et al. (2000) J. Sub.Abuse Treat., 18: 51-54

FDA Approved Medications for Treating Alcohol Dependence

  • 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

Medications for Treating Alcohol Dependence – Under Investigation

  • Medication
  • Target
  • Topiramate
  • GABA/Glutamate
  • Valproate
  • GABA/Glutamate
  • Ondansetron
  • 5-HT3 Receptor
  • Nalmefene
  • Mu Opioid Receptor
  • Baclofen
  • GABAB Receptor
  • Antalarmin
  • CRF1 Receptor
  • Rimonabant
  • CB1 Receptor

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
  • venlafaxine (Effexor)
  • AD/schizophrenia
  • clozapine (Clozaril)
  • AD/tobacco dependence
  • bupropion (Zyban)
  • AD/cocaine dependence
  • topiramate (Topamax)

NIAAA Clinician’s Guide Helping Patients Who Drink Too Much

Conclusion: Alcohol Research Strengths and Opportunities

  • Alcohol pharmacogenetics
    • human and animal models
  • Animal models
    • genes, pathways and networks, and GxE interactions
  • Epidemiology
    • longitudinal general population and high-risk studies
  • Treatment
    • behavioral
    • pharmacological


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