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Alcohol abusers are frequently vitamin and mineral deficient. Alcoholic going through withdrawal should be given large doses of thiamine along with normal doses of other vitamins and minerals. However, there has been considerable research trying to find medications which might help people dependent on alcohol to either avoid drinking or at least avoid heavy drinking. In the U.S., the FDA has approved only disulfiram (Antabuse) and naltrexone (Revia) for the medication treatment of alcoholism. Efforts are currently underway to get acamprosate (Campral) approved as well. Acamprosate is already in regular clinical use in Europe. Each has its own page above. I favor using disulfiram and acamprosate with disulfiram used in the context of family therapy. However, my favorite treatment is emetine aversion therapy either by itself with counseling (ideally family counseling) or in combination with one or both meds. The aversion therapy markedly diminishes the urge to drink. Urges have been strongly related to relapse. Although emetine aversion therapy has not been studied in random assignment studies, there are many studies with long-term follow-up. Also, rapid smoking aversion therapy of tobacco smoking has been found to be the most powerful treatment for nicotine addiction. Naltrexone and acamprosate can be safely combined (Alcohol Clin Exp Res. 2003 Jul;27(7):1123-31). Clearly, therapy must be tailored for each patient. Physicians in Addiction Medicine Reluctant to Try Hypothetical New Medicine: A survey of 1388 physicians specializing in addiction medication (65% response rate) gave each doctor four hypothetical scenarios. In each, they were asked to choose between prescribing one of two hypothetical alcoholism medications with given attributes or prescribing no medication. The effectiveness of the hypothetical medication had an fairly significant effect on the decision of whether to use it or not, but price and non-serious side-effects had little influence. However, even with an extremely favorable new medication (i.e., 80% abstinence rate, a 95% no heavy drinking rate, a 10% side effect rate, a 80% compliance rate, and a price of 25 cents), half of the physicians would not prescribe the medication. Researchers conclude that addiction medicine physicians are much less willing to use medication than physicians in other areas of medicine. Medstat.com. Using stated preference modeling to forecast the effect of medication attributes on prescriptions of alcoholism medications. Mark TL, Swait J. Value Health. 2003 Jul-Aug;6(4):474-82. Physicians in Addiction Medicine Prescribing Practices: In the same survey as above, the average percentages of physicians' patients with alcoholism who were prescribed the following medications were: 13% (naltrexone), 9% (disulfiram), 46% (antidepressants) and 11% (benzodiazepines). Almost all physicians had heard of naltrexone and disulfiram, but their self-reported level of knowledge about these medications was lower than for antidepressants. Physicians estimated that naltrexone had a small-to-medium effect size, which is what recent meta-analysis studies have concluded. Physicians' opinions about medications to treat alcoholism. Heavy Drinking Plus Low Folate Causes Chronic Disease: In a 16 year follow-up of 83,929 women 34-59 years old, women drinking more than 2 drinks per day (30g) and who had a low folate intake had 36% more chronic diseases (RR = 1.36). However, those with higher folates had much less chronic disease. Joint association of alcohol and folate intake with risk of major chronic disease in women. Harvard. Jiang R, Hu FB, Giovannucci EL, Rimm EB, Stampfer MJ, Spiegelman D, Rosner BA, Willett WC. Am J Epidemiol. 2003 Oct 15;158(8):760-71 Medication Studies The very large number of medication studies will not be reviewed here. In general, they have been very disappointing. Disulfiram (Antabuse) has been widely used but has a very major problem with patient compliance. Patients get sick if they drink within several days of taking disulfiram. It has been found of definite benefit when patients can be required to take it, e.g. with a court order and supervision, but it is only of minor benefit for the average patient in the typical setting. Combining disulfiram with family counseling has been of value. I myself have done an FDA approved study of a combination capsule of disulfiram with chlordiazepoxide (Librium) which I found of modest value, better than disulfiram alone. Unfortunately, I was unable to convince any pharmaceutical company to continue the research. Almost All Open Trials See Benefits Where There Are None. Pattison reviewed 89 medication published reports by physicians affiliated with various universities. 95% of those that were uncontrolled open trial reports claimed positive benefit from the medication but only 6% of the controlled studies found benefit despite the fact that the controlled studies were looking at exactly the same medications as the uncontrolled open trials. EM Pattison. Ten years of change in alcoholism treatment and delivery systems. Am J Psychiatry. 1977 Mar;134(3):261-6. Baclofen Helped in DB: Baclofen, a GABA B-receptor agonist, reduces self-initiated nicotine, alcohol, cocaine, and opioid use in rats. A small 39-patient DB PC study for just 30 days with alcoholics 12-24 hours after last drink treated as out-patients. There were more abstinent days and some reduced craving and anxiety with baclofen. Baclofen efficacy in reducing alcohol craving and intake: a preliminary double-blind randomized controlled study. Addolorato G, Caputo F, Capristo E, Domenicali M, Bernardi M, Janiri L, Agabio R, Colombo G, Gessa GL, Gasbarrini G. Alcohol Alcohol. 2002 Sep-Oct;37(5):504-8. Ed: This is a small, preliminary study of short duration. I will be very surprised is baclofen ends up being that useful for treating alcohol dependence. Buspirone, Lithium No Help in Alcoholism: In a DB PC 6-month study of 156 alcoholics, there was no significant difference in staying in the program, abstinence, or amount of alcohol consumed. Pharmacological treatments for alcoholism: revisiting lithium and considering buspirone. Fawcett J, Kravitz HM, McGuire M, Easton M, Ross J, Pisani V, Fogg LF, Clark D, Whitney M, Kravitz G, Javaid J, Teas G. Rush-Presbyterian. Alcohol Clin Exp Res. 2000 May;24(5):666-74 Calcium Carbimide(Temposil): Calcium carbimide has been used in other countries in a way similar to disulfiram (Antabuse). It appears to have fewer unwanted side-effects, but is unfortunately much shorter acting that disulfiram requiring a repeat dose every 12 hours. After about 15 hours, reactions to it are mild. Disulfiram, by contrast, has a considerably longer half-life with significant reactions to drinking occurring 2-3 days after the last dose. Both calcium carbimide and disulfiram can cause serious hepatitis. Diagn Histopathol. 1983 Jan-Mar;6(1):29-37 Gamma Hydroxybutyric Acid Helped in Small DB: 82 alcoholic patients were treated in a 3-month DB PC study with gamma-hydroxybutyric acid or placebo. Of 36 on GHB at the finish 11 were abstinent and 15 drinking in a controlled manner. For placebo the numbers were two and six. gamma-Hydroxybutyric acid in the treatment of alcohol dependence: a double-blind study. Gallimberti L, Ferri M, Ferrara SD, Fadda F, Gessa GL. Alcohol Clin Exp Res. 1992 Aug;16(4):673-6 Gamma Hydroxybutyric Acid Not as Good as Naltrexone: In an open but randomized study of 35 patients for 3 months of naltrexone 50 mg/day or gamma-hydroxybutyric acid 50 mg/kg t.i.d., of the gamma-hydroxybutyric who had returned to drinking all had relapsed into alcoholism while none of the naltrexone patients who had returned to drinking were drinking out of control. Univ. Bologna. Disulfiram (Antabuse) Helps in Large DB: 605 alcoholics were in a DB PC study of disulfiram, placebo, or no pill at all. Total 1 year abstinence was 20% for disulfiram vs. 16% otherwise. First drink 60 days with disulfiram vs. 40 days. Drinking days for those drinking were 49 on disulfiram vs. 86 otherwise or 43% less with disulfiram. All patients were in outpatient programs with counselors. R. Fuller, JAMA 86;256:1449 Nalmefene No Help in Alcoholism Treatment: In a 12-week DB PC study using 3 doses of nalmefene (5, 20, or 40 mg) vs. placebo in treating recently abstinent out-patient alcoholics, there was no difference in lab tests or craving, days of heavy drinking between groups, or days to first drink. A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence. A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence. Anton RF, Pettinati H, Zweben A, Kranzler HR, Johnson B, Bohn MJ, McCaul ME, Anthenelli R, Salloum I, Galloway G, Garbutt J, Swift R, Gastfriend D, Kallio A, Karhuvaara S. Medical University of South Carolina. 7/04 Neither Nefazodone (Serzone) Nor Naltrexone (Revia) Helped in DB: 183 alcohol dependents in PC DB study for 12 weeks with all patients receiving weekly psychosocial counseling. No medication benefits were noted. Naltrexone vs. nefazodone for treatment of alcohol dependence. A placebo-controlled trial. Kranzler HR, Modesto-Lowe V, Van Kirk J. Neuropsychopharmacology. 2000 May;22(5):493-503, Univ of Connecticut. Ondansetron (Zofran) Decreases Craving: In a large 256-patient 11-week DB PC study of placebo, 1 mcg, 4 mcg, and 16 mcg/kg b.i.d. of ondansetron, researchers found that ondansetron decreased craving and the number of drinkings. Ondansetron reduces the craving of biologically predisposed alcoholics. Johnson BA, Roache JD, Ait-Daoud N, Zanca NA, Velazquez M. U Texas, San Antonio. Psychopharmacology (Berl). 2002 Apr;160(4):408-13; In the same study, ondansetron (16 microg/kg twice daily) showed greater therapeutic efficacy at alleviating symptoms of overall mood disturbance, fatigue, vigor, confusion/bewilderment, and depression among EOA compared with LOA. EOA-associated improvements in mood disturbance seemed to be independent of drinking behavior. Alcohol Clin Exp Res. 2003 Nov;27(11):1773-9 Ondansetron Decreases Drinking and Increases Abstinence: Ondansetron is a serotonin-3 (5-HT3) receptor antagonist. In a 271-patients DB PC study with doses as above, ondansetron patients with early onset alcoholism had less drinking and fewer drinking days and the 4 mcg group had more abstinence, but those with late onset alcoholism did not do better while on ondansetron. U Texas, San Antonio. Ondansetron for reduction of drinking among biologically predisposed alcoholic patients: A randomized controlled trial. Johnson BA, Roache JD, Javors MA, DiClemente CC, Cloninger CR, Prihoda TJ, Bordnick PS, Ait-Daoud N, Hensler J. JAMA. 2000 Aug 23-30;284(8):963-71. Ed: This is an interesting study, but I would wait for more research before concluding that ondansetron actually helps. Sertraline (Zoloft) Didn't Help in Small DB: 83 recently detoxified alcoholics with Major Depression were given sertraline 50-150 mg/d or placebo in a 24-week DB PC study. Both groups did quite well with the placebo doing non-significantly better for both reduced drinking (relapses 23% vs. 32%) and decreased depression. Sertraline did do better for the severely depressed. Sertraline for the prevention of relapse in detoxicated alcohol dependent patients with a comorbid depressive disorder: a randomized controlled trial. Gual A, Balcells M, Torres M, Madrigal M, Diez T, Serrano L Alcohol Alcohol. 2003 Nov-Dec;38(6):619-25 Topiramate (Topamax) Helped in DB: 150 alcohol dependent in 12 week PC DB study by the Univ. of Texas, San Antonio. Topiramate (Up to 300 mg/d, $200), compared with those on placebo, had 2.88 fewer drinks per day (p=0.0006), 3.10 fewer drinks per drinking day (p=0.0009), 27.6% fewer heavy drinking days (p=0.0003), 26.2% more days abstinent (p=0.0003), and lower gamma-glutamyl transferase liver enzymes (p=0.0046). Topiramate-induced differences in craving were also significantly greater than those of placebo, of similar magnitude to the self-reported drinking changes, and highly correlated with them. Oral topiramate for treatment of alcohol dependence: a randomised controlled trial. Johnson BA, Ait-Daoud N, Bowden CL, DiClemente CC, Roache JD, Lawson K, Javors MA, Ma JZ. Lancet. 2003 May 17;361(9370):1677-85 Topiramate Helped Alcoholics in Short Study: In a 150-patient DB PC 12-week study, topiramate (escalating dose of 25 mg/d to 300 mg/d), compared with placebo, improved the odds of overall well-being (odds ratio [OR] = 2.17; P =.01); reported abstinence and not seeking alcohol (OR = 2.63; P =.001); overall life satisfaction (OR = 2.28; P =.01); and reduced harmful drinking consequences (OR = -0.07, P =.01). Oral topiramate reduces the consequences of drinking and improves the quality of life of alcohol-dependent individuals: a randomized controlled trial. Johnson BA, Ait-Daoud N, Akhtar FZ, Ma JZ. University of Texas, San Antonio. Arch Gen Psychiatry. 2004 Sep;61(9):905-12. Ed: This is the same study as above, just reported in a way to make it sound better than it really was.
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