Alcohol Use Abuse and Dependence by sammyc2007

VIEWS: 92 PAGES: 42

									                                                                                               1




                                                      Alcohol Use, Abuse, and
National Institute on Alcohol Abuse and Alcoholism




                                                           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
                                                                                                                       2




                                                                                        Ting-Kai Li, M.D.
National Institute on Alcohol Abuse and Alcoholism




                                                                                              Director
                                                                                 National Institute on Alcohol Abuse
                                                                                           and Alcoholism




                                                     http://www.niaaa.nih.gov/AboutNIAAA/DirectorsCorner/default.htm
                                                                                                                                      3



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




                                                     ● 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
National Institute on Alcohol Abuse and Alcoholism




                      Alcohol Use
                                                     4
                                                                                                                                     5




                                                            Alcohol: Our Most Primitive Intoxicant
National Institute on Alcohol Abuse and Alcoholism




                                                      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)
                                                                                                                                6



                                                      Ancient Warnings About Alcohol and Harmful Use
                                                                    Through the Ages
National Institute on Alcohol Abuse and Alcoholism




                                                      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
                                                                                                              7

                                                     Total Per Capita Consumption in Gallons of Ethanol
                                                                by State - United States, 2003
National Institute on Alcohol Abuse and Alcoholism




                                                                                                        ■DC




                                                                                 ■ 1.99 or below (10)
                                                                                 ■ 2.00-2.24 (15)
                                                                                 ■ 2.25-2.49 (16)
                                                                                 ■ 2.50 or over (10)
                                                                                                                                                                                8


                                                      Cumulative Distribution of Alcohol Consumption
                                                                   in the United States
National Institute on Alcohol Abuse and Alcoholism




                                                      65% of the
                                                                                                                   100
                                                       population are




                                                                                          Percent of Consumption
                                                       drinkers*                                                    80

                                                      Males reported                                               60
                                                       drinking 74% and
                                                                                                                    40
                                                       females 26% of all
                                                       alcohol consumed                                             20

                                                      73% of the alcohol                                            0
                                                       is consumed by                                                    0   10   20   30   40   50   60   70   80   90   100
                                                                                                                                  Percentile Group (High to Low)
                                                       10% of the
                                                       population
                                                     * Individuals who reported drinking at least one drink in past 12-months


                                                     NIAAA National Epidemiological Survey on Alcohol and Related Conditions (NESARC) (2001-2002).
                                                                                                               9




                                                        Drinking Patterns: Rates and Risks
                                                                    Moderate Drinking
National Institute on Alcohol Abuse and Alcoholism




                                                        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 .
                                                                                                                                          10




                                                                    Drinking Patterns: Rates and Risks
                                                                                      High-Risk Drinking
National Institute on Alcohol Abuse and Alcoholism




                                                        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
                                                                                                                   11




                                                           Drinking Patterns: Rates and Risks
                                                                          Binge Drinking
National Institute on Alcohol Abuse and Alcoholism




                                                     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
                                                                                                                                                       12

                                                                        U.S. Adult Drinking Patterns and Risks
                                                                               2001-2002: Odds Ratios
National Institute on Alcohol Abuse and Alcoholism




                                                      Alcohol screening limits—number of drinks:                     The Odds of Having An
                                                          In a typical WEEK—14 (men), 7 (women)                      Alcohol Use Disorder are
                                                              On any DAY— 4 (men), 3 (women)                        Increased by a Factor of. . .
                                                                                                   Percent of           Abuse         Dependence
                                                                 Drinking Pattern                 U.S. adults          without       with or without
                                                                                                aged 18 or older     dependence           abuse
                                                                                                                                       Reference
                                                     Never exceeds the weekly or daily                             Reference group
                                                                                                     72 %                               group
                                                     screening limits                                                   (1.0)
                                                                                                                                         (1.0)
                                                     Exceeds only the weekly limit                   2%                  7.8              12.4
                                                     Exceeds only the daily limit less than
                                                                                                     14 %               17.0              33.0
                                                     once a week
                                                     Exceeds only the daily limit once a week
                                                                                                     2%                 31.1              82.0
                                                     or more

                                                     Exceeds both weekly & daily limits once
                                                                                                     10 %               31.1             219.4
                                                     a week or more



                                                     NIAAA National Survey on Alcohol and Related Conditions, (2001-2002)
                                                                                                                                                                        13

                                                            Harmful Drinking Pattern Across the Lifespan
                                                            Number of Days in Past 30 Drank 5 or More Drinks
National Institute on Alcohol Abuse and Alcoholism




                                                                   4.5

                                                                    4                                                                               Males
                                                                                                                                                    Females
                                                                   3.5

                                                                    3

                                                                   2.5
                                                            Days




                                                                    2

                                                                   1.5

                                                                    1

                                                                   0.5

                                                                    0
                                                                         12   13   14   15   16   17   18   19   20    21   22-23 24-25 26-29 30-34 35-49 50-64   65+

                                                                                                                 Age

                                                     U.S. Substance Abuse and Mental Health Services Administration, 2003 National Survey on Drug Use
                                                     and Health (NSDUH)
                                                                                                                                                                                                        14


                                                                     Relative Risk of an Alcohol-Related Health
                                                                   Condition as a Function of Daily Alcohol Intake
National Institute on Alcohol Abuse and Alcoholism




                                                                       30




                                                                       25
                                                       Relative Risk




                                                                                                                50 g/day         100 g/day
                                                                       20




                                                                       15




                                                                       10




                                                                       5




                                                                       0
                                                                             Oral cavity   Esophagus   Breast       Essential       Coronary      Ischemic   Hemorrhagic Liver cirrhosis   Chronic
                                                                            and pharynx                           hypertension    heart disease    stroke      stroke                    pancreatitis

                                                                                                                       Condition

                                                     Adapted from Corrao et al. (2004), Preventive Medicine, 38:613–619
                                                                                                                                              15


                                                               Odds of Co-Occurrence of Current (12-month)
                                                             DSM-IV Alcohol Dependence and Selected Psychiatric
                                                                               Conditions
National Institute on Alcohol Abuse and Alcoholism




                                                         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.
                                                                                                                                                                       16


                                                                  Burden of Disease Attributable to Alcohol Among the 10
                                                                  Leading Risk Factors for Disease In Developed Countries
           National Institute on Alcohol Abuse and lcoholism
National Institute on Alcohol Abuse and AAlcoholism




                                                                                          Tobacco

                                                                                  Blood pressure

                                                                                           Alcohol

                                                                                       Cholesterol

                                                                                       Overweight

                                                                   Low fruit and vegetable intake

                                                                                Physical inactivity

                                                                                       Illicit drugs

                                                                                       Unsafe sex

                                                                                   Iron deficiency

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

                                                                                                        % 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
National Institute on Alcohol Abuse and Alcoholism




                       Alcohol Abuse
                                                     17
                                                                                                                                                         18
                                                               Definition and Diagnostic Criteria for Alcohol Abuse/
                                                                              Harmful Use of Alcohol
                                                                  DSM-IV Alcohol Abuse                                   ICD-10 Harmful Use
National Institute on Alcohol Abuse and Alcoholism




                                                     A. A maladaptive pattern of alcohol use leading to            A. A pattern of alcohol use that is
                                                         clinically significant impairment or distress, as             causing physical and/or mental
                                                         manifested by one or more of the following occurring          damage to health.
                                                         within a 12-month period:



                                                           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


                                                          *Ninety percent of those diagnosed as having Alcohol Abuse endorse this criterion.
                                                          Others are 20% or less (Dawson, DA. Unpublished NESARC Analysis, 2006)

                                                     B. The symptoms have never met the criteria for alcohol       B. No concurrent diagnosis of the
                                                         dependence                                                    alcohol dependence syndrome
                                                                                                                                      19



                                                      Do Alcohol Use Disorders Fall Along a Continuum
                                                                        of Severity?
National Institute on Alcohol Abuse and Alcoholism




                                                      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)
National Institute on Alcohol Abuse and Alcoholism




                      (Alcoholism)
                   Alcohol Dependence
                                                     20
                                                                                                                  21

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

                                                     1. Tolerance
National Institute on Alcohol Abuse and Alcoholism




                                                     2. Withdrawal:                         Pharmacological
                                                     relief/avoidance
                                                     3. Impaired control*
                                                        larger/longer
                                                        unsuccessful attempts to
                                                         quit/control                         Maladaptive

                                                     4. Compulsive Use*
                                                        craving (ICD-10) only)
                                                        neglect activities
                                                        time spent
                                                                                          Severity of Addiction
                                                        use despite negative
                                                          consequences

                                                      * elements of addiction
                                                                                                                                                                                     22


                                                                       Prevalence of Past-year DSM-IV Alcohol
                                                                      Dependence by Age United States, 2001-2002
National Institute on Alcohol Abuse and Alcoholism




                                                                               14%

                                                                               12%
                                                         One-Year Prevalence




                                                                               10%

                                                                               8%
                                                                                                                                Most people
                                                                               6%                                                   seek
                                                                                                                                treatment at                   Prevalence of
                                                                                                                                  this age                    DSM-IV Alcohol
                                                                               4%                                                                              Dependence in
                                                                                                                                                               2001-2002 was
                                                                                                                                                                   3.8%
                                                                               2%

                                                                               0%
                                                                                     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

                                                     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)
National Institute on Alcohol Abuse and Alcoholism




                      Etiology of Alcohol Use Disorders
                                                          23
National Institute on Alcohol Abuse and Alcoholism                                                       24




                                                     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
National Institute on Alcohol Abuse and Alcoholism




                                                            Disease
                                                Alcoholism: A Common Complex
                                                                               25
                                                                                                                                26

                                                             Developmental Trajectory of AUD
                                                            Initiation and Continuation of Drinking
National Institute on Alcohol Abuse and Alcoholism




                                                                  Initiation of       Progression            Alcoholic
                                                                   Drinking                                  Drinking




                                                     Extent of
                                                     Influence




                                                                 Environmental (familial and non familial)
                                                                 Personality/Temperament (Endophenotype)
                                                                 Pharmacological effects of ethanol (Intermediate Phenotypes)
                                                                                                                  27


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




                                                                   Genes + Environment =
                                                         different types of alcoholism with different
                                                            characteristics and levels of severity

                                                                   G1
                                                                    1
                                                                        G2
                                                                         2
                                                                                 G3
                                                                                  3
                                                                                             G4
                                                                                              4
                                                                                                  G5
                                                                                                   5



                                                                   E1
                                                                    1
                                                                        E2
                                                                         2
                                                                                 E3
                                                                                  3
                                                                                             E4
                                                                                              4
                                                                                                  E5
                                                                                                   5




                                                          Alcohol              Alcohol              Alcohol
                                                         Dependence          Dependence           Dependence
                                                          (Severe)            (Moderate)             (Mild)
                                                         G1   G2   G5                                   G3
                                                          1    2    5         G2
                                                                               2
                                                                                        G4
                                                                                         4               3

                                                         E1
                                                          1   E3   E4
                                                                    4              E2              E2
                                                                                                    2
                                                                                                             E5
                                                                                                              5
                                                               3                    2
                                                                                                        28


                                                       Between Individual Variations in Responses to
                                                                         Alcohol
                                                         (Why drink; Drink more; Drink despite)
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
                                                                                                                        29

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




                                                                                       CYTOSOL
                                                                    ADH
                                                                    ADH                  ALDH1
                                                                                         ALDH1
                                                     CH3CH2OH              CH3CHO                       CH3COOH
                                                       (mM)                 (μM)                          (mM)
                                                                                       NAD+    NADH
                                                             NAD+    NADH
                                                                                                        CH3COOH
                                                                                                          (mM)
                                                                NADH
                                                                Shuttle
                                                                                         ALDH2
                                                                                         ALDH2
                                                                           CH3CHO                       CH3COOH
                                                                                                      NAD+
                                                                                NAD+
                                                                                        NADH
                                                                                                      NADH
                                                                                                             TCA
                                                                                                             TCA

                                                                                                                  CO2
                                                                                          electron
                                                                                          electron
                                                                                         transport
                                                                                         transport                H2O

                                                      Energy Yield: 7 Kcals/g                          ATP
                                                                                                                                                             30

                                                        Age at Onset: DSM-IV Age of First Use of Alcohol,
                                                                     Nicotine, and Cannabis
National Institute on Alcohol Abuse and Alcoholism




                                                                                            35%
                                                                                                                            Age of First Alcohol Use
                                                         Percentage in each age group who




                                                                                            30%                             Age at first Nicotine Use
                                                                                                                            Age of First Cannabis Use
                                                                begin using alcohol




                                                                                            25%

                                                                                            20%

                                                                                            15%

                                                                                            10%

                                                                                            5%

                                                                                            0%
                                                                                                  5   10   15   20    25   30   35      40     45       50
                                                                                                                     Age
                                                     Source: NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003
                                                                                                                                                                                                         31

                                                      Prevalence of Lifetime Alcohol Dependence by Age of
                                                       First Alcohol Use and Family History of Alcoholism
National Institute on Alcohol Abuse and Alcoholism




                                                                                          1991-1992                                           60                    2001-2002
                                                                      60
                                                                                                                                              50
                                                                      50
                                                                                                                                              40




                                                                                                                               % Prevalence
                                                       % Prevalence




                                                                      40
                                                                                                                                              30
                                                                      30
                                                                                                                                              20
                                                                      20
                                                                                                                                              10
                                                                      10
                                                                                                                                               0
                                                                       0                                                                           <=13   14   15    16     17     18     19   20   >=21
                                                                           13   14   15     16   17    18   19     20   21                                      Age at First Use of Alcohol
                                                                                     Age at First Use of Alcohol
                                                                                                                                Source: 2001-2002 National Epidemiologic Survey on Alcohol nad Related
                                                                                                                                Conditions; Laboratory of Epidemiology and Biometry; DICBR, NIAAA,
                                                     Source: Grant and Dawson. (1988). J. Substance Abuse, 10(2):163-73
                                                                                                                                Bethesda, MD.

                                                                                                            Parental History Positive
                                                                                                            Total
                                                                                                            Parental History Negative
                                                                                                                                                   32
                                                     Daily Consumption by P and NP Rats Responding on a Two-
                                                     Bar Operant Task for Water and Different Concentrations of
                                                                             Ethanol
National Institute on Alcohol Abuse and Alcoholism




                                                               g/kg/day
                                                     Ethanol
                                                               ( ml/day)




                                                                               *p=<0.05
                                                     (ml/day)




                                                                                                               Murphy JM, Gatto GJ, McBride WJ,
                                                      Water




                                                                                                               Lumeng L, Li TK ((1989). Alcohol.
                                                                                                               6(2):127-31.

                                                                           2     5   10   15 20 25   30   40
                                                                                      % ethanol
National Institute on Alcohol Abuse and Alcoholism




                      Treatment of Alcohol Use Disorders
                                                           33
                                                                                                                                                                                            34

                                                         Treatment of, and Recovery from, Alcohol
                                                                        Dependence
                                                      Many recover, or remit,
National Institute on Alcohol Abuse and Alcoholism




                                                                                                              Past-year Status by Interval Since Onset of Dependence
                                                                                                                                                                   n=4,422
                                                       without professional                                   100%
                                                                                                              90%                                                    Abstainer

                                                       interventions                                          80%




                                                                                           % PPY Population
                                                                                                              70%                                                    Low-risk drinker

                                                      Early interventions are                                60%
                                                                                                              50%
                                                       successful in reducing                                 40%
                                                                                                                                                                     Asymptomatic risk
                                                                                                                                                                     drinker (subclinical
                                                                                                                                                                     dependence)
                                                       chronicity and severity                                30%
                                                                                                              20%                                                    Partial Remission



                                                      Treatment success rates are
                                                                                                              10%
                                                                                                               0%                                                    Still Dependent

                                                       30%-60% depending on                                            <5       5 to 9     10 to 19
                                                                                                                                 Interval (Years)
                                                                                                                                                         20+


                                                       outcome measure (e.g.,                            Dawson et al., (2005). Addiction. 2005 Mar;100(3):296-8. NIAAA National
                                                                                                         Epidemiological Survey on Alcohol and Related Conditions, 2001-2002
                                                       abstinence, heavy drinking,
                                                       social functioning)
                                                      Interventions include:
                                                         Brief intervention
                                                         Behavioral therapies (e.g., motivational enhancement, cognitive behavioral, 12-
                                                          steps)
                                                         Pharmacological therapies
                                                                                                                                      35


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




                                                                                        Screening

                                                       Prevention         Facilitated self-change     Behavioral and Medication
                                                                             Brief counseling                 Therapy




                                                                                                                          Disease
                                                                                                                         management



                                                                                                    Dependence       Dependence
                                                        None          At-risk*      Harmful use       (Early)         (Chronic)




                                                       * >4 drinks/day, 14 drinks/week (men)
                                                         >3 drinks/day, 7 drinks/week (women)
National Institute on Alcohol Abuse and Alcoholism                                                              36




                                                     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
                                                                                                                                                    37

                                                                               Behavioral Therapies
                                                     Treatment
                                                                                                 Primary Target Population(s)
National Institute on Alcohol Abuse and Alcoholism




                                                     Intervention
                                                                                         High-risk        Alcohol
                                                                                                                          Alcohol- dependent
                                                                                         drinkers         abusers

                                                     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
                                                                                                                            38


                                                     FDA Approved Medications for Treating Alcohol
                                                                   Dependence
National Institute on Alcohol Abuse and Alcoholism




                                                     Medication              Target                         Year Approved

                                                     Disulfiram              Aldehyde                          1949
                                                                             Dehydrogenase

                                                             Research from animal models over the past 25 years has
                                                                provided promising targets for pharmacotherapy

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

                                                     Naltrexone Depot        Mu Opioid Receptor                2006
                                                                                                       39




                                                       Medications for Treating Alcohol Dependence –
                                                                    Under Investigation
National Institute on Alcohol Abuse and Alcoholism




                                                     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
                                                                                                        40


                                                         Examples of NIAAA-Supported Clinical
                                                     Pharmacotherapy Trials for AUDs and Co-morbid
                                                                 Psychiatric Conditions
National Institute on Alcohol Abuse and Alcoholism




                                                     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)
                                                                                                                                                   41
                                                                                 NIAAA Clinician’s Guide
                                                                         Helping Patients Who Drink Too Much

                                                      Based on the AUDIT-C:
National Institute on Alcohol Abuse and Alcoholism




                                                         1. How often do you have a drink
                                                            containing alcohol?
                                                         2. How many drinks containing alcohol do
                                                            you have on a typical day when you are
                                                            drinking?
                                                         3. How often do you have 6 or more drinks
                                                            on an occasion?
                                                      The third question alone is:
                                                              sensitive for heavy drinking (79%) and alcohol abuse/ dependence
                                                                (81%)
                                                              specific (83%) for heavy drinking, abuse and dependence1
                                                     1
                                                      Bush et al, Arch Intern Med. 1998;158:1789-1795

                                                     Information and training materials for the NIAAA Clinician’s guide are available at:
                                                     http://pubs.niaaa.nih.gov/publications/practitioner/CliniciansGuide2005/Guide_Slideshow.htm
                                                                                                         42

                                                       Conclusion: Alcohol Research Strengths and
                                                                     Opportunities
National Institute on Alcohol Abuse and Alcoholism




                                                      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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