Abstract
Rationale
Twelve weeks of naltrexone significantly improves drinking outcomes in alcoholics; however, the clinical benefits of naltrexone decline shortly after treatment is discontinued.
Objective
The present study investigated whether extended treatment with naltrexone significantly improved drinking outcomes.
Methods
One hundred forty-six alcohol-dependent patients received broad spectrum treatment or motivational enhancement therapy and either 12 or 24 weeks of naltrexone. The primary dependent variables were percent days abstinent and percent heavy drinking days.
Results
Using an intention-to-treat analysis, there were no significant differences in percent days abstinence or percent heavy drinking days at the end of phase 2 between patients who received 24 weeks of treatment with naltrexone (\( \overline{x} = 63.23 \)) or patients who received 12 weeks of treatment with naltrexone followed by 12 weeks of treatment with placebo (\( \overline{x} = 65.82 \)). Similarly, the average percent heavy drinking days was not significantly different at the end of phase 2 between the group that received 24 weeks of naltrexone (\( \overline{x} = 21.9 \)) and the group that received 12 weeks of naltrexone followed by 12 weeks of placebo (\( \overline{x} = 22.14 \)). Medication compliance was low in the second phase of the study. Drinking outcomes declined with declining compliance whether patients were taking naltrexone or placebo.
Conclusions
The results of this study suggest that administering naltrexone beyond an initial 12 weeks of treatment may not be beneficial to all patients and should be administered along with close medical monitoring to insure compliance.
Similar content being viewed by others
References
Anton RF, Moak DH, Waid LR, Latham PK, Malcolm RJ, Dias JK (1999) Naltrexone and cognitive behavioral therapy for the treatment of out-patient alcoholics: results of a placebo-controlled trial. Am J Psychiatry 11:1758–1764
Anton RF, Moak DH, Latham PK, Waid LR, Malcolm RJ, Dias JK, Roberts JS (2001) Posttreatment results of combining naltrexone with cognitive-behavior therapy for the treatment of alcoholism. J Clin Psychopharmacol 21:72–77
Anton RF, Moak DH, Latham P, Waid LR, Myrick H, Voronin K, Thevos A, Wang W, Woolson R (2005) Naltrexone combined with either cognitive behavioral or motivational enhancement therapy for alcohol dependence. J Clin Psychopharmacol 25:349–357
Balldin J, Berglund M, Borg S, Mansson M, Bendtsen J, Gustafsson L, Halldin, Nilsson G, Willander A (2003) A 6-month controlled naltrexone study: combined effect with cognitive behavioral therapy in outpatient treatment of alcohol dependence. Alcohol Clin Exp Res 27:1142–1149
Biener L, Abrams DB (1991) The contemplation ladder: validation of a measure of readiness to consider smoking cessation. Health Psychol 10:360–365
Bohn MJ, Kranzler HR, Beazoglou D, Staehler BA (1994) Naltrexone and brief counseling to reduce heavy drinking. Am J Addictions 3:91–99
Chick J, Anton R, Checinski K, Croop R, Drummond DC, Farmer R, Labriola D, Marshall J, Moncrieff J, Morgan MY, Peters T, Ritson B (2000) A multicenter, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. Alcohol Alcohol 35:587–593
COMBINE research group (2006) Combined pharmacotherapies and behavioral interventions for alcohol dependence. The combine study: a randomized controlled trial. JAMA 295:2003–2017
Cramer JA, Mattson RH, Prevey ML, Scheyer RD, Quellette VL (1989) How often is medication taken as prescribed? A novel assessment technique. JAMA 261:3273–3277
Cramer J, Rosenheck R, Kirk G, Krol W, Krystal J (2003) Medication compliance feedback and monitoring in a clinical trial: predictors and outcomes. Value Health 6:566–573
Davidson D, Saha C, Scifres S, Fyffe J, O’Connor S, Selzer C (2004) Naltrexone and brief counseling to reduce heavy drinking in hazardous drinkers. Addict Behav 29:1253–1258
Davidson D, Gulliver S-B, Longabaugh R, Wirtz PW, Swift R (2007) Building better CBT: Is broad spectrum treatment more effective than motivational enhancement therapy for alcohol dependent patients treated with naltrexone. J Stud Alcohol Drugs 68(2):238–247
Feinn R, Kranzler HR (2005) Does effect size in naltrexone trials for alcohol dependence differ for single-site vs. multi-center studies? Alcohol Clin Exp Res 29:983–988
Garbutt JC, Kranzler HR, O’Malley SS, Gastfriend DR, Petinati HM, Silverman BL, Loewy JW, Ehrich EW (2005) Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence. JAMA 293:1617–1625
Gastpar M, Udo B, Boning J, Mann K, Schmidt LG, Soyka M, Wetterling T, Kielstein V, Labriola D, Croop R (2002) Lack of efficacy of naltrexone in the prevention of alcohol relapse: results from a German multicenter study. J Clin Psychopharmacol 22:592–598
Guardia J, Caso C, Arias F, Gual A, Sanahuja J, Ramirez M, Mengual I, Gonzalvo B, Seguara L, Trujols J, Casa M (2002) A double-blind placebo-controlled study of naltrexone in the treatment of alcohol-dependence disorder: Results from a multicenter clinical trial. Alcohol Clin Exp Res 26:1381–1387
Gulliver SB, Longabaugh R, Davidson D, Swift R (2005) The development of a broad spectrum treatment for patients with alcohol dependence in early recovery. adapting CBT for recalcitrant populations. Cogn Behav Pract 12:53–63
Heinala P, Alho H, Kuoppasalmi K, Sinclair D, Kiianmaa K, Lonngvist J (2001) Targeted use of naltrexone without prior detoxification in the treatment of alcohol dependence: a factorial double-blind, placebo-controlled trial. J Clin Psychopharmacol 21:287–292
Kranzler HR, Modesto-Lowe V, Van Kirk J (2000) Naltrexone vs. nefazodone for treatment of alcohol dependence. A placebo-controlled trial. Neuropsychopharmacology 22:493–503
Kranzler HR, Wesson DR, Billot L for the DrugAbuse Sciences Naltrexone Depot Study Group (2004) Naltrexone depot for treatment of alcohol dependence; a multicenter, randomized, placebo-controlled clinical trial. Alcoholism: Clinical & Experimental Research. Vol 28(7), 1051–1059
Krystal JH, Cramer JA, Krol WF, Kirk GF, Rosenheck RA (2001) Naltrexone in the treatment of alcohol dependence. New Engl J Med 345:1734–1739
Latt NC, Jurd S, Houseman J, Wutzke SE (2002) Naltrexone is alcohol dependence: a randomized controlled trial of effectiveness in a standard clinical setting. Med J Aust 176:530–534
Longabaugh R, Woolard RE, Nirenberg TD, Minugh AP, Becker B, Clifford PR, Carty K, Licsw, Sparadeo F, Gogineni A (2001) Evaluating the effects of a brief motivational intervention for injured drinkers in the emergency department. J Stud Alcohol Drugs 62:806–811
McGeary JE, Monti PM, Rohsenow DJ, Tidey J, Swift R, Miranda R (2006) Genetic moderators of naltrexone’s effects on alcohol cue reactivity. ACER 30:1288–1296
Miller WR, Zweben A, DiClemente CC, Rychtarik RG (1995) Motivational enhancement therapy manual: a clinical research guide for therapists treating individuals with alcohol abuse and dependence. National Institute on Alcohol Abuse and Alcoholism Project MATCH Monograph Series, vol. 2, NIAAA, Rockville, MD, USA
Monterosso JR, Flannery BA, Poettinati HM, Oslin DW, Rukstalis M, O’Brien CP, Volpicelli JR (2001) Predicting treatment response to naltrexone: The influence of craving and family history. Am J Addict 10:258–268
Monti PM, Rohsenow DJ, Swift RM, Gulliver SB, Colby SM, Mueller TI, Brown RA, Gordon A, Abrams DB, Niaura RS, Asher MK (2001) Naltrexone and cue exposure with coping and communication skills training for alcoholics: Treatment process and 1-year outcomes. Alcohol Clin Exp Res 25:1634–1647
Morris PL, Hopwood M, Whelan G, Gardiner J, Drummond J (2001) Naltrexone for alcohol dependence: a randomized controlled trial. Addiction 96:1565–1573
Namkoong K, Farren CK, O’Connor PG, O’Malley SS (1999) Measurement of compliance with naltrexone in the treatment of alcohol dependence: Research and clinical implications. J Clin Psychiatry 60:446–453
O’Brien CP, Volpicelli LA, Volpicelli JR (1996) Naltrexone in the treatment of alcoholism: a clinical review. Alcohol 13:35–39
Oslin DW, Liberto JG, O’Brien J, Krois S, Norbeck J (1997) Naltrexone as an adjunctive treatment for older patients with alcohol dependence. Am J Geriatr Psychiatry 5:324–332
Oslin DW, Berrettini W, Kranzler HR, Pettinati H, Gelernter J, Volicelli JR, O’Brian CP (2003) A functional polymorphism of the μ-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology 28:1546–1552
O’Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B (1992) Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Arch Gen Psychiatry 46:881–887
O’Malley SS, Jaffe AJ, Chang G, Rode S, Schottenfeld R, Meyer RE, Rounsaville B (1996) Six-month follow-up of naltrexone and psychotherapy for alcohol dependence. Arch Gen Psychiatry 53:217–224
O’Malley SS, Rounsaville BJ, Farren C, Namkoong K, Wu R, Robinson J, O’Connor PG (2003) Initial and maintenance naltrexone treatment for alcohol dependence using primary care vs specialty care. Arch Intern Med 163:1695–1704
Oswald LM, Wand GS (2004) Opioids and alcoholism. Physiol Behav 81:339–358
SAS Institute (1999) SAS/STAT® user’s guide (version 8). SAS Institute, Cary, NC, USA
Sobell LC, Sobell MB (1996) Alcohol timeline follow-back (TLFB) users’ manual. Addiction Research Foundation, Toronto
Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49:876–880
Volpicelli JR, Clay KL, Watson NT, O’Brien CP (1995) Naltrexone in the treatment of alcoholism: Predicting response to naltrexone. J Clin Psychiatry 56:39–44
Volpicelli JR, Rhines KC, Rhines JS, Volpicelli LA, Alterman AI, O’Brien CP (1997) Naltrexone and alcohol dependence. Arch Gen Psychiatry 54:737–742
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Davidson, D., Wirtz, P.W., Gulliver, S.B. et al. Naltrexone’s suppressant effects on drinking are limited to the first 3 months of treatment. Psychopharmacology 194, 1–10 (2007). https://doi.org/10.1007/s00213-007-0807-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-007-0807-y