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Acamprosate (Campral) was developed by German and French pharmaceutical companies and has been used in France since 1989. It is now being sold in the U.S. under the name of Campral. Looking at the research, I would suggest its use in combination with disulfiram (Antabuse). I think it is worth doing, but probably only for patients dedicated to abstinence and who have already achieved some abstinence. These medications are most effect when a family member participates by coming to appointments and by encouraging to remain compliant. Benefits appear modest but cost effective. Indeed, no treatment of alcoholism, counseling, residential rehabilitation, or medication, has more than a modest benefit in controlled studies. The FDA reviewed three European studies and one from the U.S. In the European studies, 62% remained abstinent for one year, while in the U.S. study only 46%. Most of the U.S. patients were addicted to other drugs as well and only one-third went through detox before being given acamprosate. Thus, the U.S. patients had features that would tend to decrease the chances of success. Acamprosate is currently available on line from an English pharmacy for $60 for a 28-day supply plus $15.50 shipping with a doctor's prescription which I am happy to provide if I am monitoring the care. In the U.S., it is now available for $124/month or $1500/year (Walgreens). The standard dose is six 333 mg tablets per day. The cost, while not cheap, is much less expensive than many other prescription medications still under patent. Naltrexone is $233 per month, and Antabuse $69 per month. A synthetic taurine derivative with a structural resemblance to gamma amino-butyric acid (GABA), acamprosate decreases glutamatergic transmission and modulates neuronal hyperexcitability during withdrawal from alcohol. The drug has been shown to reduce voluntary intake of alcohol in alcohol-dependent animals. It's half-life is 20-33 hours. Combining acamprosate with disulfiram (Antabuse) was found in one study to be better than either alone, which were about equal in effectiveness. In another study, disulfiram by itself appeared more effective than acamprosate. Acamprosate has been found to be about equally effective to naltrexone (ReVia), which costs twice as much. Abstinent Goal Patients Helped: In a large 601-patient 6-month DB PC study, the percentage of abstinent days did not differ significantly across groups in a priori analysis: 54% for placebo, 56% for 2 g acamprosate, 61% for 3 g acamprosate. Post-hoc analysis controlling for baseline variables and treatment exposure found acamprosate was associated with a significantly higher percentage of abstinent days than placebo (52.3% for placebo, 58.2% for 2 g, 62.7% for 3 g; P=0.01), with an even greater effect in the subgroup of 241 patients having a baseline goal of abstinence (58.1% for placebo, 70.0% for 2 g, 72.5% for 3 g; P=0.02). Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: the role of patient motivation. Mason BJ, et al. The Scripps Research Institute. . J Psychiatric Res 2006 Aug;40(5):383-93. Ed: If you subtract out those with baseline abstinence, acamprosate does not appear to have been a significant benefit for the others. Authors don't mention this, probably due to industry funding corrupting their reporting. Disulfiram Did Better: In an 8 month random assignment study of 100 alcoholic men with family members who would encourage medication compliance and accompany them for follow-up with weekly group psychotherapy also available, relapse (the consumption of >5 drinks/40 g of alcohol) occurred at a mean of 123 days with disulfiram compared to 71 days with acamprosate (P = 0.0001). 88% on DSF remained abstinent vs. 46% with ACP (P = 0.0002). However, patients allocated to ACP had lower craving than those on DSF (P = 0.002). An open randomized study comparing disulfiram and acamprosate in the treatment of alcohol dependence. de Sousa A, et al. Mumbai, India. . Alcohol Alcohol 2005 Nov-Dec;40(6):545-8. Naltrexone Added to Acamprosate Slightly Better: In a 12-week study of 236 matched patients, abstinence rates were 51% for cognitive therapy alone, 66% for CBT plus acamprosate, and 68% for CBT plus acamprosate and naltrexone. For those that did not complete the programme abstinent, the average number of days abstinent (CAD) were 45.07, 49.95, and 53.58 days, respectively. The average numbers of days to first breach (DFB) was 26.79, 26.7, and 37.32 days. Combined acamprosate and naltrexone, with cognitive behavioural therapy is superior to either medication alone for alcohol abstinence: a single centres' experience with pharmacotherapy. Feeney GF, et al. Brisbane, Australia. . Alcohol Alcohol 2006 May-Jun;41(3):321-7. Acamprosate Helped in Brazilian DB: Yet another study has documented that acamprosate reduces drinking better than placebo in patients with alcohol dependence. 75 men were studied on meds for 12 weeks then on neither med nor placebo for 12 weeks. Dosage was 666 mg t.i.d. The acamprosate group drank significantly less (P=.017) with few medication side-effects. Univ Sao Paolo. Efficacy of acamprosate in the treatment of alcohol-dependent outpatients. Baltieri DA, de Andrade AG. Rev Bras Psiquiatr. 2003 Sep;25(3):156-9 (Ed: I have personally worked on research with Dr. de Andrade in Sao Paolo. He is an excellent physician). Acamprosate Helped Teenagers in Small Austrian DB: 26 patients ages 16-19 with alcohol dependence. Half were treated with a lower dose of acamprosate (666 mg b.i.d.) for 90 days and half placebo. Seven (1 vs 6) relapsed, 5 (3 vs 2) refused to continue treatment, 3 (1 vs 2) had concurrent illness, and 2 (1 vs 1) had adverse side-effects. At the end of treatment, 7 acamprosate treated and 2 placebo-treated patients had been continuously abstinent (p = 0.0076). Mean cumulative abstinence duration was significantly greater in the acamprosate group than in the placebo group (79.8 [SD 37.5] vs 32.8 [19.0] days; p = 0.012). Acamprosate and its efficacy in treating alcohol dependent adolescents. Niederhofer H, Staffen W. Eur Child Adolesc Psychiatry. 2003 Jun;12(3):144-8. Acamprosate Didn't Help Korean Alcoholics: A DB PC 8 week study of 142 patients with severe alcohol dependence had no benefit from acamprosate (37% acamprosate vs. 32% placebo continuous abstinence). The authors speculate the severity of illness and the fact that most patients were drinking up to one or two days before starting medication and had poor family support may have contributed to a lack of benefit. Acamprosate in Korean alcohol-dependent patients: a multi-center, randomized, double-blind, placebo-controlled study. Namkoong K, Lee BO, Lee PG, Choi MJ, Lee E. Alcohol Alcohol. 2003 Mar-Apr;38(2):135-41 Acamprosate & Naltrexone Combo Best in German DB: In a 12 week DB PC study of 160 patients, the naltrexone group showed a tendency for a better outcome regarding time to first drink and time to relapse. The combination was best. Univ. Hamburg. Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Kiefer F, Jahn H, et al. Arch Gen Psychiatry. 2003 Jan;60(1):92-9; Coadministration of acamprosate with naltrexone significantly increased the rate and extent of absorption of acamprosate, as indicated by an average 33% increase in acamprosate maximum plasma concentration, 33% reduction in time to maximum plasma concentration, and 25% increase in area under the plasma concentration-time curve. U. Miami. A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Mason BJ, Goodman AM, et al. Neuropsychopharmacology. 2002 Oct;27(4):596-606; (Ed: The pharmacokinetics suggests that the acamprosate dosage might be able to be decreased without a significant loss of benefit.) Cost-Effective in Germany: 540 recently detoxed alcoholics were treated with acamprosate and 274 without medication. One year abstinence was 34% with acamprosate and 21% without. Direct costs were about 20% less with the acamprosate. Cost-effectiveness of adjuvant treatment with acamprosate in maintaining abstinence in alcohol dependent patients. Rychlik R, Siedentop H, Pfeil T, Daniel D. Eur Addict Res. 2003 Apr;9(2):59-64
Psychosocial Counseling No Added Benefit: 248 with alcohol dependence or abuse randomly assigned in 28 week study. Everyone took acamprosate; one-third got acamprosate plus minimal intervention aimed at motivational enhancement (3-weekly sessions of 20 min); and one-third acamprosate plus brief cognitive behavioral therapy (7-weekly sessions of 60 min). Acamprosate was monitored by a physician on six occasions lasting 10 min. Of 241 patients with intention to treat (ITT), 114 (47.3%) remained in treatment for the full 28 weeks; 169 of the ITT population (70.1%) were seen for follow-up. No statistically significant differences were found between treatment groups for any of the drinking outcomes either at the end of the 28 weeks of treatment or at 6-month follow-up after acamprosate stopped. There were no statistically significant differences in medication compliance, drop-out rates, or psychological distress. Does psychosocial treatment enhance the efficacy of acamprosate in patients with alcohol problems? De Wildt WA, Schippers GM, Van Den Brink W, Potgieter AS, Deckers F, Bets D. Alcohol Alcohol. 2002 Jul-Aug;37(4):375-82 Single Blind Study Reports Naltrexone Appeared Better than Acamprosate: Randomized to 1 year of naltrexone (50 mg/day) or acamprosate (1665-1998 mg/day) for 157 recently detoxified alcohol-dependent men with moderate dependence. All were patients whom a member of the family would accompany regularly to appointments. Alcohol consumption, craving and adverse events were recorded weekly for the first 3 months, and then bi-weekly, by the treating psychiatrist who was not blinded. At 3-monthly intervals, investigators who were blinded to the treatment documented patients' alcohol consumption based on patients' accounts, information given by the psychiatrists when necessary, and reports from patients' families. There was no difference between treatments in mean time to first drink (naltrexone 44 days, acamprosate 39 days) but the time to first relapse (five or more drinks in a day) was 63 days (naltrexone) versus 42 days (acamprosate) (P = 0.02). At 1 year, 41% receiving naltrexone and 17% receiving acamprosate had not relapsed (P = 0.0009). Cumulative days of abstinence were significantly greater, and the number of drinks consumed at one time and severity of craving were significantly less in the naltrexone group compared to the acamprosate group, as was the percentage of heavy drinking days (P = 0.038). More acamprosate patients were started on disulfiram during the study. Spain. Naltrexone versus acamprosate: one year follow-up of alcohol dependence treatment. Rubio G, Jimenez-Arriero MA, Ponce G, Palomo T. Alcohol Alcohol. 2001 Sep-Oct;36(5):419-25 Acamprosate Helped Spanish a Little in DB: 298 alcohol dependent patients in DB PC study of acamprosate 666 mg. t.i.d. Acamprosate was started during the withdrawal and caused no problems. In 180 study, acamprosate patients had 19 more days of abstinence although drop-out rates were equal. Continuous abstinence 35% acamprosate vs. 29%. Acamprosate during and after acute alcohol withdrawal: a double-blind placebo-controlled study in Spain. Gual A, Lehert P. Alcohol Alcohol. 2001 Sep-Oct;36(5):413-8 Acamprosate Helps Abstinence: 118 pt DB 360 days 2 g/day vs. placebo with disulfiram available to all. 73% vs. 44% 30 day abstinence and benefit still present at 270 days. Alcohol Clin Exp Res 1998 May;22(3):573-9 Acamprosate Helps Abstinence in Italian DB: 234 alcohol dependent patients in Italian PC DB for 6 months with 41% vs. 21% abstinence. Benefit lost after stopping meds. Addiction 1997 Nov;92(11):1537-46 Acamprosate Helped in Belgian Study: In a 90-day DB PC Belgium study, the abstinence rates were 41% with acamprosate vs. 15% with placebo. There were reportedly few side-effect. Efficacy and safety of acamprosate in the treatment of detoxified alcohol-dependent patients. A 90-day placebo-controlled dose-finding study. Pelc I, et al. Br J Psychiatry 1997 Jul;171:73-7 Acamprosate Helped in 2-year German Study: In a 2-year DB PC German study of 272 patients, there was a significantly higher continuous abstinence rate within the first 60 days (67% vs 50%) and also at 48 weeks (43% vs 21%, log rank P = .005). Patients on acamprosate had a significantly longer mean abstinence duration of 224 vs 163 days, or 62% vs 45% days abstinent (P < .001); however, there was no difference in psychiatric symptoms. Of the patients who were receiving acamprosate, 41% had dropped out, vs. 60% on placebo. Abstinence at 2 years was 39% with acamprosate vs. 17% with placebo even though patients had been off medications for 1 year (p<.003). Headaches and diarrhea main side-effects and not severe. Relapse prevention by acamprosate. Results from a placebo-controlled study on alcohol dependence. Sass H, et al. Aachen, Germany. Arch Gen Psychiatry 1996 Aug;53(8):673-80 Acamprosate Helped in One Study, Not Another: DB 455 pt 360 day Austrian study. 18% vs. 7% total abstinence and 30% more abstinent days. Lancet 1996 May 25;347(9013):1438-42. One Belgium study of severe hospitalized alcoholics found no benefit at 3 months in DB. J Pharm Belg 1996 Mar-Apr;51(2):65-8 First Acamprosate DB Study Reported in 1985: French study is first mentioned on PubMed and found useful. Lancet 1985 May 4;1(8436):1014-6 Acamprosate May Impair Free Recall: 2 gm/d in 7 day DB of healthy. Interacts with N-methyl-D-aspartate receptors, a subtype of glutamate receptors. No effect on mood, short-term memory.psychomotor, attention, or concentration. J Stud Alcohol 1999 Mar;60(2):172-5 Thomas E. Radecki, M.D., J.D. modern-psychiatry.com
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