Prevalence of Alcohol Use Disorders

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Prevalence of Alcohol Use Disorders
NIAAA National Epidemiologic Survey onAlcohol
and Related Conditions (NESARC)
Any Alcohol Use Disorder 17.6 million (8.5)
Alcohol Dependence 7.9 million (3.8)
Alcohol Abuse 9.7 million (4.7)
NIAAA National Institute on Alcohol Abuse and
Alcoholism Grant BF, et al. Arch Gen Psychiatry.
200461807-816.
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Epidemiology of Use and Abstention
Percent
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Epidemiology of Heavy Use
Heavy Use Women gt 1 drink / day
Men gt 2 drinks / day
Percent
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12-mo. Prevalence of DSM-IV AUD Diagnoses
Men
Women
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Medications Approved in the US for Treatment of
Alcohol Dependence

• Disulfiram (Antabuse) 1949
• Naltrexone (ReVia) 1994
• Acamprosate (Campral) 2004
• Long-Acting Naltrexone (Vivitrol) 2006

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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

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Opioids

• Acute alcohol increases plasma b-Endorphin levels

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Opioids

• Opioid antagonists reduce alcohol drinking

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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

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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 (N35) Placebo (N35)
0.2
0.1
0.0
1
0
2
3
4
5
6
7
8
9
10
11
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Number of Weeks Receiving Medication
Volpicelli et al., Arch Gen Psychiatry, 1992
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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
p lt 0.025
30
20
10
0
Weeks
Placebo (n 28)
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COMBINE (Anton et al., 2006)
ASAM, 2007
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VA cooperative study
From Krystal et al 2001
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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!

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

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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

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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).

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Laboratory models to study alcohol-naltrexone
interactions

• Human laboratory-based paradigms have been used
  to evaluate naltrexones 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, OMalley et al 2002
• Importantly, effects observed in laboratory
  studies similar to those seen in clinical trials

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Alcohol Self-Administration Model (OMalley,
Krishnan-Sarin et al., 2002)
Day 0
Day 6
Day 7
Choice Block 1 500 pm
Choice Block 2 600 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)
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Naltrexone and FH of alcoholism
From Krishnan-Sarin et al., 2007