Medications shown to be effective in standard use:

Naltrexone: Blocks opioid receptors resulting in reduced craving and reduced reward in response to drinking, contraindicated in patients using opioids. Oral dose: 50 mg daily.

Injectable naltrexone-extended release : Blocks opioid receptors with 30 days duration. Contraindicated in patients using opioids. Deep intramuscular gluteal injection, 380 mg once monthly.

Acamprosate: Alters glutamate and GABA neurotransmitter systems. Contraindicated in severe renal impairment. Oral dose: 666 mg 3 times daily.

Disulfiram: Inhibits up of the aldehyde dehydrogenase resulting in a buildup of acetaldehyde and a reaction of blushing, sweating, nausea and tachycardia if the patient drinks alcohol. Oral dose: 250 mg daily.

Medications shown to be effective in some studies:

Topiramate: Thought to work by stimulating GABA neurotransmission and reducing glutamate transmission. Initial oral dose: 25 mg increasing to target dose of 200 mg per day.

Bromocriptine: A dopamine agonist. Oral dose: up to 5 mg three times daily.

Ondansetron: A serotonin 3 receptor antagonist found to be more effective in early-onset alcoholics than late-onset alcoholics. Oral dose: 4 mcg twice daily.

Varenicline: A nicotinic receptor partial agonist, oral dose up to 2 mg per day.

Memantine: A NMDA receptor antagonist has been shown to reduce alcohol craving.

Corticotrophin receptor antagonists: Have been shown in numerous laboratory studies to reduce alcohol self administration during withdrawal. This class of drugs are not presently available for clinical use.

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Medications for treating alcohol dependence.

Medication managment.

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A dopamine agonist bromocriptine is an effective treatment for alcohol abuse.

Bromocriptine Is an Effective Treatment for Alcohol Abuse

50 alcoholic patients received placebo (n = 24, 4 female, mean age = 40) or bromocriptine (n = 26, 5 female, mean age = 42) for 6 months. Total drug-taking evaluation scale evaluated 4 items: abuse situation, social functioning, social belonging and psychic status – each on a 1 – 9 scale (1 – 3: normal; 4 – 6: symptomatic; and 7 – 9: illness) – total scale range 4 – 36. Craving rated from 0 = none to 5 = very strong. Global evaluation at 6 months. Bromocriptine given 2.5 mg three times daily months 1 – 3, and then 5 mg three times daily months 4 – 6. (Constructed from data in Borg, V. et al. Act Psych Scand, 68: 100, 1983) ©2006 NBEP
The dopamine agonist bromocriptine is more effective in individuals with the risk allele of the dopamine D2 receptor.

Bromocriptine decreases craving in alcoholic subjects with the Taq 1A allele
The serotonin 3 receptor antagonist ondansetron is more effective in early onset alcoholics.

Ondansetron, a Serotonin 3 Receptor Antagonist, is a More Effective Treatment in Early Onset Alcoholics Than Late Onset Alcoholics

20 Alcoholics with onset of dependence before age 25 (early onset) and 20 alcoholics with onset of dependence after age 25 (late onset) received Ondansetron oral solution 4 µg twice daily for 8 weeks. Ondasetron reduced drinks/day and drinks per drinking day for both early and late onset alcoholics but was more effective for early onset alcoholics. * p <.01 within group ** p <.001 within group (Constructed from data in Kranzler, H.R. et al. Alcohol Clin Exp Res, 27: 1150, 2003) ©2010 NBEP
Varenicline reduces alcohol intake.

A Possible Treatment for Alcoholism: Reducing Efficacy of the Nicotine Acetylcholine Receptor Reduces Ethanol Intake

A nicotine acetylcholine receptor partial agonist at the alpha 4 beta 2 receptor (varenicline) which is a functional antagonist in the presence of nicotine and reduces the efficacy of alpha 4 beta 2 nicotinic acetylcholine receptors, selectively decreases ethanol seeking and consumption. The effect is consistent with other findings showing that nicotine increases ethanol-induced dopamine release in the nucleus accumbens. Ethanol seeking was measured using operant self-administration of oral drinking. Low and high continuous intake of ethanol was for 8 weeks before treatment. Repeated treatment was conducted on rats with 8 weeks continuous high ethanol intake. (Constructed from data in Steensland, P. et al. PNAS, 104: 12518, 2007) ©2007 NBEP
Varenicline reduces alcohol craving and drinking in smokers.

Varenicline Reduces Alcohol Induced Subjective Alcohol Craving and Other Alcohol Subjective Effects and Reduces Alcohol Drinking in Heavy Drinkers who Smoke

20 healthy subjects (mean age 35, 80% male) who, on average, drank over 6 drinks per episode and smoked 20 cigarettes per day were randomized to receive varenicline (2 mg/day last 2 days) (n = 10) or placebo (n = 10) for 7 days before a laboratory session where they ingested alcohol (.3 g/kg), and drank up to 4 alcohol drinks (.15 g/kg alcohol per drink). Increased alcohol craving was associated with increased alcohol drinking and subjects on varenicline had increased abstinence during the alcohol drinking period. (abstinence: 8/10 varenicline; 3/10 placebo, p < .03) (Constructed from data in McKee, S. et al Biological Psychiatry, 66: 185 - 90, 2009) ©2011 NBEP
A NMDA receptor antagonist reduces craving.

The N-Methyl-D-Aspartic Acid (NMDA) Receptor Antagonist Reduces Alcohol Craving

38 male alcohol dependent patients (mean age 39) who were sober for a mean of 22 days were studied on 3 separate days while an inpatient. Placebo or memantine were given on separate days by month at time 0 and visual analogue scales were used to measure subjective effects. The alcohol cue was to smell and handle the alcohol drink of their choice for 15 min. Memantine produced mild alcohol-like effects and attenuated cue-induced alcohol craving. (Constructed from data in Krupitsky, E.M. et al. Am J Psych, 164: 519, 2007) ©2007 NBEP
Antagonism of CRF receptors reduces alcohol intake during withdrawal.

Antagonism of Corticotrophin-Releasing Factor-1 Receptors Reduces Ethanol Self-Administration during Ethanol Withdrawal

After rats were trained to orally self-administer ethanol, one group was intermittently exposed to 14 hrs per day of ethanol vapors and 10 hrs of room air for 4 weeks, and controls just had room air. Rats were tested 2 hrs after withdrawal from the vapors. Ethanol vapor produced a blood alcohol level of 173 – 189 mg/dL (over 2 times the legal level for driving of 80 mg/dL). All 3 drugs tested produced a dose response curve (only highest dose used is illustrated) and lever-pressing for water was not affected. (Constructed from data in Funk, C.K. et al. Biol Psych, 61: 78, 2007) ©2007 NBEP