1 National Institute on Alcohol Abuse and Alcoholism 1 Alcohol Use, Abuse, and Dependence National Institute on Alcohol Abuse and Alcoholism National Institutes of Health

2 National Institute on Alcohol Abuse and Alcoholism National Institute on Alcohol Abuse and Alcoholism Mission

3 National Institute on Alcohol Abuse and Alcoholism Alcohol Use

4 National Institute on Alcohol Abuse and Alcoholism 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: one12-ounce can or bottle of beer orwine cooler, one5-ounce glass of wine, or1.5 ounces of 80-proof distilled spirits.

5 National Institute on Alcohol Abuse and Alcoholism Nearly 3 in 10 U.S. adults engage in these high-risk drinking patterns 1 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 High-Risk Drinking

6 National Institute on Alcohol Abuse and Alcoholism 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

7 National Institute on Alcohol Abuse and Alcoholism U.S. Adult Drinking Patterns and Risks : Odds Ratios NIAAA National Survey on Alcohol and Related Conditions, ( ) 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 limit2 % Exceeds only the daily limit less than once a week 14 % Exceeds only the daily limit once a week or more 2 % Exceeds both weekly & daily limits once a week or more 10 %

8 National Institute on Alcohol Abuse and Alcoholism U.S. Substance Abuse and Mental Health Services Administration, 2003 National Survey on Drug Use and Health (NSDUH) Harmful Drinking Pattern Across the Lifespan Number of Days in Past 30 Drank 5 or More Drinks

9 National Institute on Alcohol Abuse and Alcoholism 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

10 National Institute on Alcohol Abuse and Alcoholism DisorderOdds Anxiety Disorders2.6x Mood Disorders (especially Major Depression)4.1x Personality Disorders 4.0x Antisocial Personality Disorder7.1x Drug Dependence 36.9x Nicotine Dependence6.4x NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, Odds of Co-Occurrence of Current (12-month) DSM-IV Alcohol Dependence and Selected Psychiatric Conditions

11 National Institute on Alcohol Abuse and Alcoholism Burden of Disease Attributable to Alcohol Among the 10 Leading Risk Factors for Disease In Developed Countries The World Health Report 2002: N ational I nstitute on A lcohol A buse and A lcoholism

12 National Institute on Alcohol Abuse and Alcoholism Alcohol Abuse

13 National Institute on Alcohol Abuse and Alcoholism DSM-IV Alcohol AbuseICD-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 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)

14 National Institute on Alcohol Abuse and Alcoholism 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 NIAAA National Longitudinal Alcohol Epidemiological Survey (NLAES)

15 National Institute on Alcohol Abuse and Alcoholism Alcohol Dependence (Alcoholism)

16 National Institute on Alcohol Abuse and 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)  neglect activities  time spent  use despite negative consequences Severity of Addiction

17 National Institute on Alcohol Abuse and Alcoholism Prevalence of Past-year DSM-IV Alcohol Dependence by Age United States, yrs. - NIAAA NESARC ( Grant et al. (2004) Drug and Alcohol Dependence, 74: ) 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 was 3.8%

18 National Institute on Alcohol Abuse and Alcoholism Etiology of Alcohol Use Disorders

19 National Institute on Alcohol Abuse and Alcoholism 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

20 National Institute on Alcohol Abuse and Alcoholism Alcoholism: A Common Complex Disease

21 National Institute on Alcohol Abuse and Alcoholism Extent of Influence Initiation of Drinking ProgressionAlcoholic Drinking Environmental (familial and non familial) Personality/Temperament (Endophenotype) Pharmacological effects of ethanol (Intermediate Phenotypes) Developmental Trajectory of AUD Initiation and Continuation of Drinking

22 National Institute on Alcohol Abuse and Alcoholism Gene-Environment Interactions in Alcohol Dependence

23 National Institute on Alcohol Abuse and Alcoholism !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 Between Individual Variations in Responses to Alcohol (Why drink; Drink more; Drink despite)

24 National Institute on Alcohol Abuse and Alcoholism Metabolism of Ethanol and Acetaldehyde in Hepatocyte

25 National Institute on Alcohol Abuse and Alcoholism 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

26 National Institute on Alcohol Abuse and Alcoholism Treatment of Alcohol Use Disorders

27 National Institute on Alcohol Abuse and Alcoholism Treatment of, and Recovery from, Alcohol Dependence

28 National Institute on Alcohol Abuse and Alcoholism Heterogeneity of Treatment Populations: Severity

29 National Institute on Alcohol Abuse and Alcoholism 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

30 National Institute on Alcohol Abuse and Alcoholism 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  Behavioral Therapies Selected References: Moyer et al. (2002) Addiction, 97: ; Miller et al. (2002) Addiction, 97: ; O’Farrell et al. (2000) J. Sub.Abuse Treat., 18: 51-54

31 National Institute on Alcohol Abuse and Alcoholism MedicationTargetYear Approved DisulfiramAldehyde Dehydrogenase 1949 Research from animal models over the past 25 years has provided promising targets for pharmacotherapy NaltrexoneMu Opioid Receptor1994 AcamprosateGlutamate and GABA- Related 2004 Naltrexone DepotMu Opioid Receptor2006 FDA Approved Medications for Treating Alcohol Dependence

32 National Institute on Alcohol Abuse and Alcoholism MedicationTarget TopiramateGABA/Glutamate ValproateGABA/Glutamate Ondansetron5-HT 3 Receptor NalmefeneMu Opioid Receptor BaclofenGABA B Receptor AntalarminCRF1 Receptor RimonabantCB1 Receptor Medications for Treating Alcohol Dependence – Under Investigation

33 National Institute on Alcohol Abuse and Alcoholism Examples of NIAAA-Supported Clinical Pharmacotherapy Trials for AUDs and Co-morbid Psychiatric Conditions Co-morbiditiesMedication(s) AD/Depressionnaltrexone; sertraline AD/Bipolarvalproate; naltrexone AUD/anxiety disordersvenlafaxine (Effexor) AD/schizophreniaclozapine (Clozaril) AD/tobacco dependencebupropion (Zyban) AD/cocaine dependencetopiramate (Topamax)

34 National Institute on Alcohol Abuse and Alcoholism NIAAA Clinician’s Guide Helping Patients Who Drink Too Much