Alcohol Abuse: DSM IV * (Harmful Drinking) 1. Failure to fulfill obligations at work, school, or home. 2. Recurrent use in hazardous situations. 3. Legal problems related to alcohol. 4. Continued use despite alcohol-related social problems. ------------ *American Psychiatric Association, 1994
Alcohol Dependence: DSM IV * 1. Withdrawal symptoms. 2. Use of larger amounts than intended (“tolerance”). 3. Unsuccessful attempts to control use. 4. Great deal of time spent or recovering from use. 5. Important social or occupational activities reduced. 6. Use despite alcohol-related physical or psychological problems. ------------ *American Psychiatric Association, 1994
A continuum of cognitive deficits from mild to severe
Impairments of visuo-spatial functioning
Perseveration is failed problem-solving strategies
Memory Sensory Input Sensory Memory Short-Term Memory Long-Term Memory Rehearsal Retrieval Transfer (encoding) Transfer (encoding) Alcohol primarily interferes with the transfer of Information from short-term to long-term storage Atkinson and Shiffrin (1968)
Medications: Alcohol Reward Reduction Reduction of protracted withdrawal? Dopamine inhibition Glutamate stabilization Topiramate (Topanax) May be effective in an older subset of alcoholic population Serotonin-3-receptor Antagonist Ondansetron Reduction of protracted withdrawal? Glutamate stabilization Acamprosate (Campral) Opioid antagonists Naltrexone (ReVia, Vivitrol) Nalmefene May also have efficacy for reducing cocaine use ALDH blockers Disulfiram (Antabuse) Calcium Carbimide
FDA-Approved Pharmacotherapies for Alcohol Dependence Drug Class Mini-Profile Disulfiram (antabuse ®) * Inhibits aldehyde dehydrogenase * When taken with alcohol, ↑ (acetaldehyde) leads to nausea, dizziness, headache, flushing * Decreases desire to drink * Poor tolerability profile * Black box warning, safety issues
ADH (Alcohol Dehydrogenase) ALDH (Aldehyde Dehydrogenase) Site of Action of Antabuse: Blockade of ALDH produces Increase in nauseating Acetaldehyde which is Normally cleared rapidly
FDA-Approved Pharmacotherapies for Alcohol Dependence Drug Class Mini-Profile Naltrexone (ReVia ®) * Opioid antagonist * Binds to opioid receptors, thus blocking alcohol reward pathways * Black box warning, safety issues FDA = US Food and Drug Administration. Antabuse is a registered trademark of Odyssey Pharmaceuticals, Inc. ReVia is a registered trademark of the DuPont Merck Pharmaceutical Company Source: O’Connor PG, et al, N Engl J Med. 1998;338:592-602.
Naltrexone Studies TSF Twelve Step Facilitation Krystal et al, 2001 + + Guardia et al, 2002 + + Morris et al, 2001 + + Compliant patients only Chick et al, 2000 Report Studies + + + Cognitive-behavioral Anton et al, 1999 + + Relapse prevention Treatment completions Volpicelli et al, 1997 + + Supportive/Coping Skills O’Malley et al, 1992 + + + Intensive multimodality Volpicelli et al. 1992 Older Studies Craving Reduction Drinking Reduction Slowed Response Additional Therapy NTX Study
Had a greater reduction in the number of heavy drinking days than those treated with placebo
Patients receiving VIVITROL 380 mg who were abstinent for a week prior to treatment initiation*
Were more likely to maintain complete abstinence throughout the 6-month study
Had a greater reduction in the number of any drinking days
Had a greater reduction in their number of heavy drinking days
VIVITROL full Prescribing Information. Alkermes, Inc. *All patients treated with psychosocial support
VIVITROL Prolonged Abstinence Patients abstinent for 7 days prior to treatment initiation Data on file. Alkermes, Inc.
VIVITROL Significantly Reduced Drinking Days Patients abstinent for 7 days prior to treatment initiation Data on file. Alkermes, Inc.
VIVITROL Significantly Reduced Heavy Drinking Days Patients abstinent for 7 days prior to treatment initiation Data on file. Alkermes, Inc.
Most Common Adverse Events * Nausea was generally mild in intensity, lasted 2 to 3 days, and was less common with subsequent injections. Discontinuation rate due to nausea was 2% ** Discontinuation rate due to injection site reactions was 3% VIVITROL full Prescribing Information. Alkermes, Inc. 12 20 Fatigue 50 65 Injection site reaction** 4 13 Dizziness 18 6 11 12 Vomiting 21 Headache 29 Nausea* Placebo (%) VIVITROL (%)