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Prevalence of Alcohol Use Disorders

Prevalence of Alcohol Use Disorders. NIAAA – National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Any Alcohol Use Disorder 17.6 million (8.5%). Alcohol Abuse 9.7 million (4.7%). Alcohol Dependence 7.9 million (3.8%).

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Prevalence of Alcohol Use Disorders

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  1. Prevalence of Alcohol Use Disorders NIAAA – National Epidemiologic Survey onAlcohol and Related Conditions (NESARC) Any Alcohol Use Disorder 17.6 million (8.5%) 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;61:807-816.

  2. Epidemiology of Use and Abstention Percent

  3. Epidemiology of Heavy Use Heavy Use Women: > 1 drink / day Men: > 2 drinks / day Percent

  4. 12-mo. Prevalence of DSM-IV AUD Diagnoses 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

  7. Opioids • Acute alcohol increases plasma b-Endorphin levels

  8. Opioids • Opioid antagonists reduce alcohol drinking

  9. 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

  10. 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 0 1 2 3 4 5 6 7 8 9 10 11 12 Number of Weeks Receiving Medication Volpicelli et al., Arch Gen Psychiatry, 1992

  11. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 Vivitrex (n = 28) 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 < 0.025 30 20 10 0 Weeks Placebo (n = 28)

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

  13. VA cooperative study From Krystal et al 2001

  14. 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!

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

  16. 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

  17. 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

  18. 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).

  19. 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

  20. Alcohol Self-Administration Model(O’Malley, Krishnan-Sarin et al., 2002) 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)

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

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