The overall safety profile of naltrexone is good; however, care must be taken in prescribing the drug to certain patient populations; e.g., naltrexone shows a dose-dependent hepatotoxicity (package insert) and is therefore contraindicated in patients with significant hepatic impairment, which is frequently encountered in alcohol-dependent populations.
The clinical trials of naltrexone have typically been conducted in patients without significant impairment in hepatic function. Another consequence of the hepatic impact of naltrexone is the possibility of drug-drug interactions.
Kim et al. (2001) potentially clinically significant interaction has been reported between naltrexone and nonsteroidal anti-inflammatory drugs; these researchers found elevated liver function tests in study participants receiving both medications, although the doses of naltrexone used in this study were higher than the typical 50 mg daily dose.
Naltrexone is not appropriate for use with patients taking prescribed or illicit opioid drugs. Antagonism of the effects of these drugs at opiate receptors will generally precipitate an opiate withdrawal syndrome. As a result, naltrexone would be contraindicated for methadone-maintained patients with alcohol dependence or those patients with needs for narcotic analgesics, and a small proportion of patients will not be able to tolerate naltrexone, primarily because of nausea.
Pettinati et al. (2000)* combined medication management and motivational enhancement regimen was used to provide individualized clinical care while monitoring pharmaco-therapy or individualized counseling. The study found that for compliant subjects, much lower relapse rates were experienced in the naltrexone group compared to the control group; however, for noncompliant subjects there was no advantage to naltrexone over placebo.
This 3-month intervention used 50-100 mg of naltrexone daily or an identical placebo. Compliance with the intervention developed by these researchers was significantly higher than with individualized counseling (83% versus 55% for trial completion and 77% versus 60% for medication compliance.
Kranzler et al. (2000)*
This study found no significant difference on outcome measures between control group using placebo and those using naltrexone.
In general, among all groups, treatment compliance predicted slightly less drinking, but there were no significant differences didentified between the two groups.
Monti et al. (2001)*
Naltrexone showed results superior to placebo, while subjects took medication; however, the effects did not persist. Overall, cue exposure training with coping and communication skills training showed better long-term outcomes.
Anton & Randall (2005)*
It has generally been shown, possibly because of blockade of the reinforcement or rewarding effects of alcohol, that naltrexone will most likely inhibit a heavy drinking episode after initial "slip drinking."
Several trials showed that naltrexone also increased the percentage of days abstinent.
Howard & Vaughn (2004)*
More studies that experimentally manipulate the psychosocial treatments delivered in conjunction with opioid antagonists are still required. To date, most studies have compared groups receiving naltrexone to a given placebo, all of whom received standard agency-based psychosocial interventions.
Future research should include longer follow-up periods, ensure that they evaluate treatment effects in patients who are compliant with treatment, and examine the effects of treatment on the extent of drinking in patients who relapse.
Source: Cited in Mason (2005) unless otherwise indicated with (*).
Naltrexone is a long-acting oral opiate antagonist that many researchers and clinicians believe has useful effects in treating alcohol abuse and the symptoms that are associated with withdrawal from alcohol (Bean & Nemitz, 2004). The research showed that naltrexone appears to be well-tolerated and effective in many patients by helping them to stop resumption of episodes of binge drinking. To date, there have been more than a dozen studies concerning the various aspects of using naltrexone as an adjunct to alcohol treatment; however, the research also showed that additional studies will be needed in the future to determine more specific doses, the optimal duration of treatment, and whether subtypes of alcoholics would benefit from using naltrexone (Heather & Stockwell, 2004). Finally, strategies to support medication compliance may need to be emphasized to optimize the therapeutic outcomes associated with naltrexone regimens (Mason, 2005).
Ait-Daoud, N., & Johnson, B.A. (1999). Medications to treat alcoholism. Alcohol Research & Health, 23(2), 99.
Anton, R.F., & Randall, C.L. (2005). Measurement and choice of drinking outcome variables in the COMBINE study. Journal of Studies on Alcohol, 66(4), 104.
Bhagar, H.A., & Schmetzer, a.D. (2006). New antidipsotropics. Annals of the American Psychotherapy Association, 9(4), 29.
Bean, P., & Nemitz, T. (2004). Drug treatment: What works? New York: Routledge.
Carpenter, K.M., Kleber, H.D., Nunes, E.V., Rothenberg, J.L., & Sullivan, M.A. (2006). Behavioral therapy to augment oral naltrexone for opioid dependence: A ceiling on effectiveness? American Journal of Drug and Alcohol Abuse, 32(4), 503.
Chick, J., Anton, R., Checinski, K., Croop, R., Drummond, D.C., Farmer, R., Labiola, D., Marshall, J., Moncrief, J., Morgan, M.Y., Peters, T., & Ritson, B. (2000). A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. Alcohol and Alcoholism, 35, 587-93.
Croop, R.S., Faulkner, E.B., & Labriola, D.F. (1997). The safety profile of naltrexone in the treatment of alcoholism: Results from a multicenter usage study. The Naltrexone Usage Study Group. Archives of General Psychiatry, 54, 1130-35.
Heather, N., & Stockwell, T. (2004). The essential handbook of treatment and prevention of alcohol problems. Hoboken, NJ: Wiley.
Kim, S.W., Grant, J.E., Adson, D.E., & Remmel, R.P. (2001). A preliminary report on possible naltrexone and nonsteroidal analgesic interactions. Journal of Clinical Psychopharmacology, 21, 632-34.
Kranzler, H.R., Modesto-Lowe, V., & Von Kirk, J. (2000). Naltrexone vs. nefazodone for treatment of alcohol dependence: A placebo-controlled trial. Neuropsychopharmacology, 22, 493-503
Krystal, J.H., Cramer, J.A., Krol, W.F., Kirk, G.F., & Rosenheck, R.A. (2001). Veterans Affairs naltrexone cooperative study 425 group: Naltrexone in the treatment of alcohol dependence. New England Journal of Medicine, 345, 1734-39.
Mason, B.J. (2005). Rationale for combining acamprosate and naltrexone for treating alcohol dependence. Journal of Studies on Alcohol, 66(4), 148.
Monti, P.M., Rohsenow, D.J., Swift, R.M., Gulliver, S.B., Colby, S.M., Mueller, T.I., Brown, R.A., Gorolon, a., Abrams, D.B., Niaura, R.S., & Asher, M.K. (2001). Naltrexone and cue exposure with coping and communication skills training for alcoholics: Treatment process and 1-year outcomes. Alcoholism: Clinical and Experimental Research, 25, 1634-47.
Morris, P.L., Hopwood, M., Whelan, G. et al. (2001). Naltrexone for alcohol dependence: A randomized controlled trial. Addiction, 96, 1565-73.
O'Malley, S.S., Jaffe, a.J., Rode, S., & Rounsaville, B. (1996). Experience of a 'slip' among alcoholics treated with naltrexone or placebo. American Journal of Psychiatry, 153, 281- 83.
Oslin, D., Liberto, J.G., O'Brien, J. et al. (1997). Naltrexone as…