Abstract
Objective
Alcohol abuse in patients with schizophrenia is associated with psychiatric and social complications. While two medications have been approved by the Federal Drug Administration (FDA) for the treatment of alcoholism: disulfiram and naltrexone, no medications have been approved for individuals with alcohol dependence and comorbid schizophrenia. The purpose of this study was to evaluate the efficacy of naltrexone in alcohol-abusing schizophrenic patients.
Method
Thirty-one patients with schizophrenia and comorbid alcohol abuse or dependence were treated for 12 weeks in an outpatient study using naltrexone or placebo in a randomized, double-blind fashion in addition to their neuroleptic medication. Patients also participated in a weekly therapy using cognitive-behavioral drug relapse prevention strategies combined with skills training. Outcomes included drinking measured by the time line follow-back method, craving using the Tiffany Craving Questionnaire, psychotic symptoms using the Positive and Negative Symptoms Scale (PANSS), side effects and a measures of abnormal involuntary movements.
Results
There were no significant differences in treatment exposure or medication compliance between groups. Naltrexone treated patients had significantly fewer drinking days, heavy drinking days (>5 drinks) and reported less craving compared to the placebo treated patients. Naltrexone did not affect symptoms of schizophrenia, such as psychosis. The medication was well tolerated and there were no group differences in side effects.
Conclusions
These data suggest that naltrexone may be an effective medication for individuals with comorbid alcohol dependence and schizophrenia. Given the widespread problems associated with alcohol misuse in this population, and the lack of effective pharmacotherapies, these findings represent an exciting clinical development.
Similar content being viewed by others
References
Batki S, Dimmock J, Cornell M, Wade M, Carey K, Maisto, S (2002) Directly observed naltrexone treatment of alcohol dependence in schizophrenia: preliminary analysis. Alcohol Clin Exp Res 26:83A
Croop RS, Faulkner EB, Labriola DF (1997) The safety profile of naltrexone in the treatment of alcoholism. Results from a multicenter usage study. The Naltrexone Usage Study Group. Arch Gen Psychiatry 54:1130–1135
Davidson D, Swift R, Fitz E (1996) Naltrexone increases the latency to drink alcohol in social drinkers. Alcohol Clin Exp Res 20:732–739
Derogatis LR, Lipman RS, Rickels K, Uhlenhuth EH, Covi L (1974) The Hopkins Symptom Checklist (HSCL): a self-report symptom inventory. Behav Sci 19:1–15
Dixon L (1999) Dual diagnosis of substance abuse in schizophrenia: prevalence and impact on outcomes. Schizophr Res 35:S93–100
Drake RE, Xie H, McHugo GJ, Green AI (2000) The effects of clozapine on alcohol and drug use disorders among patients with schizophrenia. Schizophr Bull 26:441–449
Gerding LB, Labbate LA, Measom MO, Santos AB, Arana GW (1999) Alcohol dependence and hospitalization in schizophrenia. Schizophr Res 38:71–75
Guy W (1976) ECDEU assessment manual for psychopharmacology. Publication 76-338, Washington D.C.
Hansen L, Larsen N (1982) Metabolic interaction between perphenazine and disulfiram. Lancet 2:1472
Hedeker D, Gibbons R, Davis J (1991) Random regression models for multicenter clinical trials data. Psychopharmacol Bull 27:73–77
Kavanagh D, McGrath J, Saunders J, Dore G, Clark D (2002) Substance misuse in patients with schizophrenia: epidemiology and management. Drugs 62:743–755
Kay SR, Fiszbein A, Opler LA (1987) The positive and negative symptom scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276
Koob GF (2000) Neurobiology of addiction. Toward the development of new therapies. Ann N Y Acad Sci 909:170–185
Kranzler H, Van Kirk J (2001) Efficacy of naltrexone and acamprosate for alcoholism treatment: a meta-analysis. Alcohol Clin Exp Res 25:1335–1341
Krystal J, Cramer J, Krol W, Kirk G, Rosenheck R (2001) Naltrexone in the treatment of alcohol dependence. N Engl J Med 345:1734–1739
Marra D, Warot D, Berlin I, Hispard E, Notides C, Tilikete S, Payan C, Lepine J, Dally S, Aubin H (2002) Amisulpride does not prevent relapse in primary alcohol dependence: results of a pilot randomized, placebo-controlled trial. Alcohol Clin Exp Res 26:1545–1552
Maxwell S, Shinderman MS (2000) Use of naltrexone in the treatment of alcohol use disorders in patients with concomitant major mental illness. J Addict Dis 19:61–69
Mueser K, Noordsy DL, Fox L, Wolfe R (2003) Disulfiram treatment for alcoholism in severe mental illness. Am J Addict 12:242–252
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 49:881–887
O’Malley SS, JA, Rode S, Rounsaville BJ (1996) Experience of a “slip” among alcoholics treated with naltexone or placebo. Am J Psychiatry 153:281–283
O’Malley SS, Krishnan-Sarin S, Farren C, Sinha R, Kreek J (2002) Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo-pituitary-adrenocortical axis. Psychopharmacologia 160:19–29
Petrakis I, Trevisan L, D’Souza DC, Gil R, Krasnicki S, Boutros N, Cooney N, Krystal JH (1999) CSF monoamine metabolite and beta-endorphin levels in recently detoxified alcoholics and healthy controls: prediction of alcohol cue-induced craving. Alcohol Clin Exp Res 23:1336–1341
Petrakis IL, Trevisan L, Boutros NN, Limoncelli D, Cooney NL, Krystal JH (2001) Effect of tryptophan depletion on alcohol cue-induced craving in abstinent alcoholic patients. Alcohol Clin Exp Res 25:1151–1155
Petrakis IL, Buonopane A, O’Malley SS, Cermik O, Trevisan L, Boutros NN, Limoncelli D, Krystal JH (2002) The effect of tryptophan depletion on alcohol self-administration in non-treatment seeking alcoholic individuals. Alcohol Clin Exp Res 26:969–975
Pickar D, Vartanian F, Bunney WE, Maier HP, Gastpar MT, Prakash R, Sethi BB, Lideman R, Belyaev BS, Tsutsulkovskaja MVA, Jungkunz G, Medopil N, Verhowven W, Praag H (1982) Short-term nalaxone administration in schizophrenic and manic patients. Arch Gen Psychiatry 39:313–319
Pickar D, Bunney W, Douillet P, Sethi B, Sharma M, Vartanian M, Lideman R, Naber D, Leibl K, Yamashita I, Koyama T, Verhoven W, Vartanian F, Morozov P, Khac T (1989) Repeated naloxone administration in schizophrenia: a phase II World Health Organization study. Biol Psychiatry 25:440–448
Project Match Research Group (1997) Matching alcoholism treatments to client heterogeneity: project MATCH posttreatment drinking outcomes. J Stud Alcohol 58:7–29
Regier DA, Farmer ME, Rae DS, Locke BZ, Keith SJ, Judd LL, Goodwin FK (1990) Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study [see comments]. JAMA 264: 2511–2518
Roberts L, Shaner A, Eckman T (1999) Overcoming addictions: skills training people for people with schizophrenia. W.W. Morton & Company, New York
Salloum IM, Cornelius JR, Thase ME, Daley DC, Kirisci L, Spotts C (1998) Naltrexone utility in depressed alcoholics. Psychopharmacol Bull 34:111–115
Sernyak MJ, Glazer WM, Heninger GR, Charney DS, Woods SW, Petrakis IL, Krystal JH, Price LH (1998) Naltrexone augmentation of neuroleptics in schizophrenia. J Clin Psychopharmacol 18:248–251
Shaw G, Majumdar S, Waller S, MacGarvie J, Dunn G (1987) Tiapride in the long-term management of alcoholics of anxious or depressive temperament. Br J Psychiatry 150:164–168
Sobell LC, Sobell MB (1992) Timeline follow-back: a technique for assessing self-reported alcohol consumption. In: Litten R, Allen J (eds) Measuring alcohol consumption. Humana Press, Clifton, N.J.
Spitzer RL, Williams JB, Gibbon M, First MB (1992) The structured clinical interview for DSM-III-R (SCID). I: History, rationale, and description. Arch Gen Psychiatry 49:624–629
Swift RM, Whelihan W, Kuznetsov O, Buongiorno G, Hsuing H (1994) Naltrexone-induced alterations in human ethanol intoxication. Am J Psychiatry 151:1463–1467
Tiffany ST, Singleton E, Haertzen CA, Henningfield JE (1993) The development of cocaine craving questionnaire. Drug Alcohol Depend 34:19–28
Volpicelli JR, Alterman A, Hayashida M, O’Brien CP (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49:876–880
Volpicelli JR, Watson NT, King AC, Sherman CE, O’Brien CP (1995) Effect of naltrexone on alcohol “high” in alcoholics. Am J Psychiatry 152:613–615
Wiesbeck G, Weijers H, Lesch O, Glasser T, Toennes P, Boening J (2001) Flupenthixol decanoate and relapse prevention in alcoholics: results from a placebo-controlled study. Alcohol 36:329–334
Acknowledgments
Support for this study was provided by NARSAD (PI=Petrakis), the Veterans Affairs MERIT grant (PI=Petrakis), the VA-Yale Alcoholism Research Center (PI=Krystal), and the VISN I Mental Illness Research and Clinical Center (MIRECC) (PI=Rounsaville) and the National Institute on Alcohol Abuse and Alcoholism (K02 AA00171=O’Malley and K02 AA00261=Krystal). The authors would like to thank Rachel Alpert, Diana Limoncelli, Adam Linkov and Ran Wu for their assistance in preparing the manuscript.
Author information
Authors and Affiliations
Consortia
Corresponding author
Additional information
An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-004-1881-z
Preliminary results from this study were presented at the Society of Biological Psychiatry 57th Annual Scientific Convention, Philadelphia, Pa., USA in May 2002. The VA Naltrexone Study Collaboration Group: West Haven: Diana Congdon, Ned Cooney, Roberto Gil, Kathy Keegan, Debra Miles, Alison Oville, Barbara Peluse, Louis Trevisan; Northampton: Lynn Gordon, John Reino, Wayne Costello, Christopher Cryan; Bedford: Nitigna Desai, Marylee Losardo, Doreen Farrell, Barbara E. Rofman. W. Costello is deceased.
Rights and permissions
About this article
Cite this article
Petrakis, I.L., O’Malley, S., Rounsaville, B. et al. Naltrexone augmentation of neuroleptic treatment in alcohol abusing patients with schizophrenia. Psychopharmacology 172, 291–297 (2004). https://doi.org/10.1007/s00213-003-1658-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-003-1658-9