1. Prevalence of Alcohol Use Disorders
1st Round Reprint Version
Prevalence of Alcohol Use Disorders
NIAAA – National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)
Any Alcohol Use Disorder
17.6 million (8.5%)
Purpose:
To provide current data on the prevalence of alcohol use disorders in the United States
Key Points:
The 12-month ( ) prevalences of alcohol use disorders were determined by DSM-IV criteria of abuse and dependence through NIAAA diagnostic interviews (Alcohol Use Disorder and Associated Disabilities Interview Schedule [AUDADIS-IV]) of 43,093 respondents
Currently, approximately 17.6 million adults (8.5%) in the United States meet the medical criteria for a diagnosis of an alcohol use disorder
In the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), conducted by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) among adults in , it was estimated that
9.7 million persons (4.7%) were alcohol abusers
7.9 million persons (3.8%) were alcohol dependent
Source: Grant BF, Stinson FS, Dawson DA, et al. Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders:results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2004; 61:
Alcohol Abuse
9.7 million (4.7%)
Alcohol Dependence
7.9 million (3.8%)
NIAAA= National Institute on Alcohol Abuse and Alcoholism
Grant BF, et al. Arch Gen Psychiatry. 2004;61:

2. Epidemiology of Use and Abstention
Percent
This is a graph of past-year alcohol use and abstention as assessed by the first wave of NESARC. A age related decrease in alcohol use can be seen, with a particularly large drop late in life (after age 64).

3. Epidemiology of Heavy Use
Women: > 1 drink / day Men: > 2 drinks / day
Percent
This is a graph of past year heavy drinking as assessed by the first wave of NESARC. Heavy drinking was defined as greater than one drink per day for women and greater than two drinks per day for men. Again, a strong, age-related decrease in heavy drinking is apparent.

4. 12-mo. Prevalence of DSM-IV AUD Diagnoses
This is a graph of past year AUDs as assessed by the first wave of NESARC. The dark portion of the bars represents alcohol dependence and the light portion of the bars represents alcohol abuse. Once again, there is a strong age-related decline in alcohol pathology. Especially notable is that fact that, for both men and women, alcohol dependence is twice as prevalent among year olds as among any other age group.
Men
Women

5. Medications Approved in the US for Treatment of Alcohol Dependence
Disulfiram (Antabuse): 1949
Naltrexone (ReVia): 1994
Acamprosate (Campral): 2004
Long-Acting Naltrexone (Vivitrol): 2006

6. Naltrexone Non-specific opioid receptor antagonist
Dose dependent binding to m, d and k opioid receptors
FDA approved as adjunctive pharmacotherapy for the treatment of alcoholism

8. Opioids
Acute alcohol increases plasma b-Endorphin levels

9. Opioids
Opioid antagonists reduce alcohol drinking

10. Clinical trials Naltrexone has been shown to
Increase percentage of days abstinent from alcohol
Reduce number of drinks/drinking day
Increase time to relapse
Decrease craving for alcohol

11. Naltrexone (Revia) in the Treatment of Alcohol Dependence
1st Round Reprint Version
Naltrexone (Revia) in the Treatment of Alcohol Dependence
1.0
0.9
0.8
0.7
0.6
Cumulative Proportion with No Relapse
0.5
0.4
0.3
Naltrexone (N=35)
Placebo (N=35)
0.2
0.1
0.0
SLIDE 41: Cumulative Relapse Rate
Relapse rates presented as a survival analysis indicate a
substantial difference between the placebo and naltrexone
treated groups 56 1 2 3 4 5 6 7 8 9 10 11 12
Number of Weeks Receiving Medication
Volpicelli et al., Arch Gen Psychiatry, 1992

12. Effect of Long-Acting Naltrexone on Maintenance of Abstinence
1st Round Reprint Version
Effect of Long-Acting Naltrexone on Maintenance of Abstinence
Subjects with 4-day lead-in abstinence
100 90 80 70 60
Percent without Relapse 50 40 30
p < 0.025 20 10 1 2 3 5 4 6 7 8 10 9 11 12 13 15 14 16 17 18 20 19 21 22 23 25 24 26 27 28 30 29 31
Weeks
Placebo (n = 28)
Vivitrex (n = 28)

13. COMBINE (Anton et al., 2006)
ASAM, 2007

14. VA cooperative study
From Krystal et al 2001

15. Cochrane review (Srisurapanont and Jarusuraisin 2002)
NTX treatment can decrease the chance of alcohol relapse for 36% as compared to placebo treatment. In addition, the treatment is likely to reduce the chance of returning to drinking for 13%.
Short-term treatment of NTX for alcoholism gives a meaningful benefit in preventing a relapse.
Small to Modest efficacy!

16. Identifying predictors of robust treatment response to naltrexone could improve clinical practice

17. Potential predictors of naltrexone response
Family history of alcoholism
Monterosso et al., 2001; Rubio et al., 2005
OPRM1 m opioid receptor gene polymorphisms
Oslin et al., 2003
Age of onset of alcohol abuse
Rubio et al., 2005
Antisocial traits and heavier drinkers
Rohsenow et al., 2007
Higher level of alcohol craving
Volpicelli et al., 1995
Consistent drinking patterns
Gueorguieva et al 2007

18. Laboratory models
Human clinical laboratory paradigms can be used to model a variety of behaviors in controlled conditions.
Careful experimental manipulations to understand the mechanisms underlying a behavior.
Can be used to evaluate medication signals following a shorter treatment period

19. Laboratory models-Alcohol
In the field of alcohol research, controlled human laboratory studies have been used to study
different populations of drinkers
(e.g., social drinkers, dependent drinkers, women, high-risk individuals),
different types of cues
(e.g., stress, social drinking, solitary drinking, peer influences),
different types and schedules of alcohol
(e.g., beer, wine, hard liquor, IV alcohol; fixed doses, scheduled administration, ad-lib drinking).

20. Laboratory models to study alcohol-naltrexone interactions
Human laboratory-based paradigms have been used to evaluate naltrexone’s effects in
Social drinkers
e.g. Swift et al 1994, King et al 1997
Non-treatment seeking alcohol dependent drinkers
e.g. Anton et al 2004; Drobes et al 2004, Krishnan-Sarin et al 2007, O’Malley et al 2002
Importantly, effects observed in laboratory studies similar to those seen in clinical trials

21. Alcohol Self-Administration Model (O’Malley, Krishnan-Sarin et al
Day 0
Day 6
Day 7
Choice Block #1
5:00 pm
Choice Block #2
6:00 pm
7 pm
4 pm
Outpatient
Treatment
Alcohol Reactivity
craving
Ad-Lib Period
4 drinks per choice period (.015 g/dl)
$12 tab per choice period
Naltrexone
pretreatment
MET Intervention Discharge
Priming Drink
(.03 g/dl)

23. Naltrexone and FH of alcoholism
From Krishnan-Sarin et al., 2007