Naltrexone (Revia) has been found of some helpful in the treatment of alcohol abuse and dependence.  However, its benefit has often appeared to be slight and probably inferior to disulfiram although both medications may be used additively since they work in very different ways.  Unfortunately, naltrexone is more expensive at $200 per month vs. $20-$25 per month for disulfiram (Antabuse) and $104 per month for acamprosate (Campral).  Acamprosate has been found cost-effective in a couple European reports.  I doubt that the same is true for naltrexone.  While the two studies comparing acamprosate to naltrexone have slightly favored naltrexone, overall, the acamprosate studies appear much more favorable that naltrexone.

Acamprosate-Naltrexone Combination Slightly Better Than Naltrexone, then Acamprosate: A 12-week 160-patient DB PC study found the combination non-signficantly better in time to first drink, time to relapse, and percentage time abstinent. 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

Naltrexone Helped in Primary Care Follow-up But not significantly in Cognitive Behavior Therapy: A random assignment Yale study of 197 alcohol dependent adults with naltrexone 50mg/d  with Primary Care or Cognitive Behavior Therapy found that patients did equally well at 12-week whether in Primary Care follow-up or CBT (84% vs. 86% avoiding persistent heavy drinking). The patients avoiding heavy drinking  were then continued in Primary Care or CBT and began 24 week DB PC studies of naltrexone or placebo.  Placebo patients did more poorly than than naltrexone patients in the Primary Care group (80% vs. 51%) but not significantly worse in the CBT group (83% vs. 70%). Initial and maintenance naltrexone treatment for alcohol dependence using primary care vs. specialty care: a nested sequence of 3 randomized trials. O'Malley SS, Rounsaville BJ, Farren C, Namkoong K, Wu R, Robinson J, O'Connor PG. Arch Intern Med. 2003 Jul 28;163(14):1695-704

Naltrexone Modest Benefit in European DB: 118 alcohol dependent patients in a 6-month DB PC study with half of each group also in cognitive-behavior therapy found a lower level of drinking (p=.04) with naltrexone. CBT only delayed the onset of the first heavy drinking day. A 6-month controlled naltrexone study: combined effect with cognitive behavioral therapy in outpatient treatment of alcohol dependence. Balldin J, Berglund M, Borg S, Mansson M, Bendtsen P, Franck J, Gustafsson L, Halldin J, Nilsson LH, Stolt G, Willander A. Alcohol Clin Exp Res. 2003 Jul;27(7):1142-9

Naltrexone of Modest Benefit in DB: 118 alcohol dependents in a PC DB study for 6 months found those assigned to naltrexone 50mg QD did somewhat better (p=.046).  The addition of 7 sessions of cognitive behavioral counseling also appeared to be of mild benefit and was in part additive to naltrexone.  A 6-month controlled naltrexone study: combined effect with cognitive behavioral therapy in outpatient treatment of alcohol dependence. Balldin J, Berglund M, Borg S, Mansson M, Bendtsen P, Franck J, Gustafsson L, Halldin J, Nilsson LH, Stolt G, Willander A.

Naltrexone No Benefit in German DB: A study of 171 detoxified alcohol dependents found naltrexone 50 mg/d did no better than placebo. Lack of efficacy of naltrexone in the prevention of alcohol relapse: results from a German multicenter study. Gastpar M, Bonnet U, Boning J, Mann K, Schmidt LG, Soyka M, Wetterling T, Kielstein V, Labriola D, Croop R. J Clin Psychopharmacol. 2002 Dec;22(6):592-8

Naltrexone Minor Benefit in Spanish DB: A PC DB 12 week study of 202 alcohol dependents. Naltrexone was well-tolerated and seemed to reduce relapse rate to heavy drinking No differences found in other alcohol consumption variables between naltrexone and placebo. Although the naltrexone group showed a tendency to consume fewer drinks per drinking day and had a longer time to first drink, differences were not statistically significant. A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol-dependence disorder: results from a multicenter clinical trial. Guardia J, Caso C, Arias F, Gual A, Sanahuja J, Ramirez M, Mengual I, Gonzalvo B, Segura L, Trujols J, Casas M. Alcohol Clin Exp Res. 2002 Sep;26(9):1381-7

Naltrexone Added to Anti-Psychotic for Dual Diagnosis Schizophrenics: 31 patients with schizophrenia and alcohol abuse were in a DB PC 12-week.  Those on naltrexone had fewer drinking days, less binge drinking, and less craving. Yale. Naltrexone augmentation of neuroleptic treatment in alcohol abusing patients with schizophrenia. Petrakis IL, O'Malley S, Rounsaville B, Poling J, McHugh-Strong C, Krystal JH. Psychopharmacology (Berl). 2003 Nov 21

Naltrexone of Minor Benefit in Meta-Analysis: 19 controlled trials were found. In comparison to placebo, two of four short-term primary outcomes were significantly in favor of naltrexone. Those were number of patients who return to drinking (61% in naltrexone group vs. 69% in placebo group)[NNT = 14] and percentage or number of drinking days [WMD (95% CI) = -4.52 (-5.29 to -3.75)]. However, the short-term discontinuation rates were high and not different between naltrexone and placebo groups [RR = 0.96]. No medium-term outcomes of naltrexone and placebo groups showed any significant difference after the completion of naltrexone treatment for three to six months. However, those who were regularly treated with naltrexone treatment in both short and medium terms consumed smaller amounts of alcohol than placebo-treated patients. Opioid antagonists for alcohol dependence. Srisurapanont M, Jarusuraisin N. Cochrane Database Syst Rev. 2002;(2):CD001867.  Ed: This review study means that it takes $8400 in medications given to 14 patients in order to prevent one patient from relapsing in the first 3 months of treatment with no clear benefit over a larger period of time.

Nalmefene Some Benefit in DB: 105 detoxified alcohol dependents in PC DB for 12 weeks found greater abstinence with nalmefene (p<.02). Nalmefene is a newer opioid antagonist that is structurally similar to naltrexone but with a number of potential pharmacological advantages for the treatment of alcohol dependence, including no dose-dependent association with toxic effects to the liver, greater oral bioavailability, longer duration of antagonist action, and more competitive binding with opioid receptor subtypes that are thought to reinforce drinking. A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence. Mason BJ, Salvato FR, Williams LD, Ritvo EC, Cutler RB. Arch Gen Psychiatry. 1999 Aug;56(8):719-24

Naltrexone Helped in Australian DB: 101 alcohol dependents in 12 week PC DB study of naltrexone 50 mg/d. Naltrexone did better than placebo (P = 0.042) especially in the first 6 weeks of the trial. The median time to relapse was 90 days for naltrexone, compared with 42 days for placebo. In absolute numbers, 19 of 56 patients (33.9%) taking naltrexone relapsed, compared with 27 of 51 patients (52.9%) taking placebo (P = 0.047). Naltrexone was well tolerated. No psychosocial treatment was provided. Naltrexone in alcohol dependence: a randomised controlled trial of effectiveness in a standard clinical setting. Latt NC, Jurd S, Houseman J, Wutzke SE. Med J Aust. 2002 Jun 3;176(11):530-4

Naltrexone Clear Benefit in One Australian DB: 111 alcohol dependents in 12 week PC DB study of naltrexone 50 mg/d found a lower rate of relapse with naltrexone (p<.001). Naltrexone for alcohol dependence: a randomized controlled trial. Morris PL, Hopwood M, Whelan G, Gardiner J, Drummond E. Addiction. 2001 Nov;96(11):1565-73

Large VA Study Finds No Benefit Naltrexone: A very large 627 patient study with one-third on naltrexone for 12 months, one-third on naltrexone for 3 months then placebo, and one-third on placebo.  There was no benefit after either 3 months or 12 months. Naltrexone in the treatment of alcohol dependence. Krystal JH, Cramer JA, Krol WF, Kirk GF, Rosenheck RA; Veterans Affairs Naltrexone Cooperative Study 425 Group. N Engl J Med. 2001 Dec 13;345(24):1734-9

Thomas E. Radecki, M.D., J.D.

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