Alcohol Use, Abuse, and Dependence

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Alcohol Use, Abuse, and Dependence

• National Institute on Alcohol Abuse and
  Alcoholism
• National Institutes of Health

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National Institute on Alcohol Abuse and
Alcoholism Mission
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Alcohol Use
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Drinking Patterns Rates and RisksModerate
Drinking
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Drinking Patterns Rates and RisksHigh-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
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Drinking Patterns Rates and RisksBinge 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
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U.S. Adult Drinking Patterns and Risks2001-2002
Odds Ratios
Alcohol screening limitsnumber of drinks In a typical WEEK14 (men), 7 (women)On any DAY 4 (men), 3 (women) Alcohol screening limitsnumber of drinks In a typical WEEK14 (men), 7 (women)On any DAY 4 (men), 3 (women) The Odds of Having An Alcohol Use Disorder are Increased by a Factor of. . . 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
Exceeds both weekly daily limits once a week or more 10 31.1 219.4
NIAAA National Survey on Alcohol and Related
Conditions, (2001-2002)
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Harmful Drinking Pattern Across the Lifespan
Number 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
Adapted from Corrao et al. (2004), Preventive
Medicine, 38613619
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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
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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
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Alcohol Abuse
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Definition and Diagnostic Criteria for Alcohol
Abuse/Harmful Use of Alcohol
DSM-IV Alcohol Abuse ICD-10 Harmful Use

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)
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Do Alcohol Use Disorders Fall Along a Continuum
of Severity?

• Data from NIAAAs 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)
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Alcohol Dependence(Alcoholism)
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Elements of Alcohol Dependence DSM-IV and
ICD-10(3 of 7 during one year required for
diagnosis)
1. Tolerance 2. Withdrawal relief/avoidance Pharmacological
3. Impaired control Maladaptive
larger/longer unsuccessful attempts to quit/control Maladaptive
Maladaptive
4. Compulsive Use Maladaptive
craving (ICD-10) only) Maladaptive
neglect activities time spent use despite negative consequences Severity of Addiction
elements of addiction
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Prevalence of Past-year DSM-IV Alcohol
Dependence by Age United States, 2001-2002
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 dependence are complex
  behavioral traits influenced by many factors
• genetic and biological responses
• environmental influences
• stages of development, from childhood to early
  adulthood

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Alcoholism A Common Complex Disease
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Developmental Trajectory of AUDInitiation and
Continuation of Drinking
Initiation of Drinking
Progression
Alcoholic Drinking
Extent of Influence
Environmental (familial and non familial)
Personality/Temperament (Endophenotype)
Pharmacological effects of ethanol (Intermediate
Phenotypes)
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Gene-Environment Interactions in Alcohol
Dependence
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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
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Metabolism of Ethanol and Acetaldehyde in
Hepatocyte
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Age at Onset DSM-IV Age of First Use of Alcohol,
Nicotine, and Cannabis
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Treatment of Alcohol Use Disorders
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Treatment of, and Recovery from, Alcohol
Dependence
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Heterogeneity of Treatment Populations Severity
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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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Behavioral Therapies
Treatment Intervention Primary Target Population(s) Primary Target Population(s) 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 ?
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FDA Approved Medications for Treating Alcohol
Dependence
Medication Medication Target Target Year Approved Year Approved

Disulfiram Disulfiram Aldehyde Dehydrogenase 1949 1949 1949
Research from animal models over the past 25 years has provided promising targets for pharmacotherapy Research from animal models over the past 25 years has provided promising targets for pharmacotherapy Research from animal models over the past 25 years has provided promising targets for pharmacotherapy Research from animal models over the past 25 years has provided promising targets for pharmacotherapy

Naltrexone Naltrexone Mu Opioid Receptor 1994 1994 1994
Acamprosate Acamprosate Glutamate and GABA-Related 2004 2004 2004
Naltrexone Depot Naltrexone Depot Mu Opioid Receptor 2006 2006 2006

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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
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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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NIAAA Clinicians Guide Helping Patients Who
Drink Too Much