Co-occurring hepatitis C, substance use, and psychiatric illness: Treatment issues and developing integrated models of care
Hepatitis C virus (HCV) infection is transmitted by injection drug use and associated with psychiatric conditions. Patients with drug use or significant psychiatric illness have typically been excluded from HCV treatment trials noting the 1997 National Institutes of Health Consensus Statement on HCV that indicated active drug use and major depressive illness were contraindications to treatment of HCV infection. However, the 2002 NIH Consensus Statement recognized that these patients could be effectively treated for HCV infection and recommended that treatment be considered on a case-by-case basis. Treating HCV infection in these patients is challenging, with drug use relapse possibly leading to psychosocial instability, poor adherence, and HCV reinfection. Interferon therapy may exacerbate preexisting psychiatric symptoms. Co-occurring human immunodeficiency virus or hepatitis B virus provide additional challenges, and access to ancillary medical and psychiatric services may be limited. Patients with co-occurring HCV infection, substance use, and psychiatric illness can complete interferon treatment with careful monitoring and aggressive intervention. Clinicians must integrate early interventions for psychiatric conditions and drug use into their treatment algorithm. Few programs or treatment models are designed to manage co-occurring substance use, psychiatric illness, and HCV infection and therapy. The National Institute on Drug Abuse convened a panel of experts to address the current status and the long-range needs through a 2-day workshop, Co-occurring Hepatitis C, Substance Abuse, and Psychiatric Illness: Addressing the Issues and Developing Integrated Models of Care. This conference report summarizes current data, medical management issues, and strategies discussed.
KeywordsComorbidities HIV HCV Psychiatric illness Treatment
Hoofnagle JH, Tralka TS. Introduction: The National Institutes of Health Consensus Development conference: management of hepatitis C. Hepatology
. 1997;26(suppl 1):1S.Google Scholar
Seeff LB, Hoofnagle JH Appendix: the National Institutes of Health Consensus Development Conference Management of Hepatitis C 2002. Clin Liver Dis
. 2003;7:261–287.CrossRefPubMedGoogle Scholar
Sherman KE. Implications of peginterferon use in special populations infected with HCV. Semin Liver Dis
. 2003;23(suppl 1):47–52.PubMedGoogle Scholar
Zeuzem S, Heathcote EJ, Shiffman ML, et al. Twelve weeks of follow-up is sufficient for the determination of sustained virologic response in patients treated with interferon alpha for chronic hepatitis C. J Hepatol
. 2003;39:106–111.CrossRefPubMedGoogle Scholar
Community Epidemiology Work Group. Epidemiologic trends in drug abuse. In: Proceedings of the Community Epidemiology Work Group December 2001
ed. Moira O’Brian. Vol. 1. Bethesda, MD: National Institute on Drug Abuse, NIH, DHHS; 2002: 1–68. NIH Publication 02-5109.Google Scholar
Patrick DM, Buxton JA, Bigham M, Mathias RG. Public health and hepatitis C. Can J Public Health
. 2000;91(suppl 1):S18–S23.PubMedGoogle Scholar
McCarthy JJ, Flynn N. Hepatitis C in methadone maintenance patients: prevalence an public policy implications. J Addict Dis
. 2001;20:19–31.CrossRefPubMedGoogle Scholar
Quaglio G, Lugoboni F, Pajusco B et al. Facors associated with hepatitis C virus infection in injection and noninjection drug users in Italy. Clin Infect Dis
. 2003;37:33–40.CrossRefPubMedGoogle Scholar
Hagan H, Des Jarlais DC. HIV and HCV infection among injection drug users. Mount Sinai J Med
. 2000;67:423–428.Google Scholar
Osher FC, Goldberg RW, McNary SW, Essock SM, Butterfield MI, Rosenberg SD, Substance abuse and the transmission of hepatitis C among persons with severe mental illness. Psychiatr Serv
. 2003;54:842–847.CrossRefPubMedGoogle Scholar
Klinkenberg WD, Caslyn RJ, Morse GA, et al. Prevalence of human immunodeficiency virus, hepatitis B, and hepatitis C among homeless persons with co-occurring severe mental illness and substance use disorders. Compr Psychiatry
. 2003;44:293–302.CrossRefPubMedGoogle Scholar
Zdilar D, Franco-Bronson K, Buchler N, Locala JA, Younossi ZM. Hepatitis C, interferon alfa, and depression. Hepatology
. 2000;31:1207–1211.CrossRefPubMedGoogle Scholar
Forton MD, Taylor-Robinson SD, Thomas HC. Cerebral dysfunction in chronic hepatitis C infection. J Viral Hepat
. 2003;10:81–86.CrossRefPubMedGoogle Scholar
Miyaoka H, Otsubo T, Kamijima K, Ishii M, Onuki M, Mitamura K. Depression from interferon therapy in patients with hepatitis C. Am J Psychiatry
. 1999;156:1120–1129.PubMedGoogle Scholar
Pariante CM, Orru MG, Baita A, Farci MG, Carpiniello B. Treatment with interferon-alpha in patients with chronic hepatitis and mood or anxiety disorders. Lancet
. 1999;354:131–132.CrossRefPubMedGoogle Scholar
DiClemente CC, Carbonari JP, Montgomery RP, Hughes SO. The Alcohol Abstinence Self-Efficacy scale. J Stud Alcohol
. 1994;55:141–148.PubMedGoogle Scholar
McLellan AT, Luborsky L, Woody GE, O’Brien CP. An improved diagnostic instrument for substance abuse patients: the Addiction Severity Index. J Nerv Mental Dis
. 1980;168:26–33.Google Scholar
WHO ASSIST Working Group. The WHO Alcohol, Smoking and Substance Involvement Screening Test (ASSIST): development, reliability and feasibility. Addiction
. 2002;97:1183–1194.CrossRefGoogle Scholar
Babor TF, Higgins-Biddle JC, Saunders JB, Monteiro M. AUDIT—the Alcohol Use Disorders Identification Test: guidelines for use in primary health care. World Health Organization, Department of Mental Health and Substance Abuse, 2001. Accessed September 3, 2004. Available at: http://www.who.int/substance_abuse/PDFfiles/auditbro.pdf.Google Scholar
Bradley KA, Bush K, Dobie DJ, et al. Two brief alcohol-screening tests from the Alcohol Use Disorders Identification Test (AUDIT): validation in a female Veterans Affairs patient population. Arch Intern Med
. 2003;163:821–829.CrossRefPubMedGoogle Scholar
Bohn MJ, Babor TF, Kranzler HR. The Alcohol Use Disorders Identification Test (AUDIT): validation of a screening instrument for use in medical settings. J Stud Alcohol
. 1995;56:423–432.PubMedGoogle Scholar
Reinert DF, Allen JP. The alcohol Use Disorders Identification Test (AUDIT): a review of recent research. Alcohol Clin Exp Res
. 2002;26:272–279.CrossRefPubMedGoogle Scholar
Bush K, Kivlahan DR, McDonell MB, Fihn SD, Bradley KA. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Arch Intern Med
. 1998;158:1789–1795.CrossRefPubMedGoogle Scholar
Drake RE, Essock SM, Shaner A, et al. Implementing dual diagnosis services for clients with severe mental illness. Psychiatr Serv
. 2001;52:469–476.CrossRefPubMedGoogle Scholar
Svanborg PM, Asberg M. A comparison between the Beck Depression Inventory (BDI) and the self-rating version of the Montgomery Asberg Depression Rating Scale (MADRS). J Affect Disord
. 2001;64:203–216.CrossRefPubMedGoogle Scholar
Beck AT, Steer RA, Ball R. Comparison of Beck Depression Inventories-IA and II in psychiatric outpatients. J Pers Assess
. 1996;67:588–597.CrossRefPubMedGoogle Scholar
Flemenbaum A, Zimmermann RL. Inter- and intra-rater reliability of the Brief Psychiatric Rating Scale. Psychol Rep
. 1973;32:783–792.PubMedGoogle Scholar
NIAAA. Helping Patients with alcohol problems: a health practitioners guide. January 2003. NIH Publication 03-3769. Accessed September 3, 2004. Available at: http://www.niaaa.nih.gov/publications/Practitioner/HelpingPatients.htm.Google Scholar
Fiellin DA, Reid MC, O’Connor PG: Screening for alcohol problems in primary care. Arch Intern Med
. 2000;160:1977–1989.CrossRefPubMedGoogle Scholar
Brown RL, Rounds LA. Conjoint screening questionnaires for alcohol and other drug abuse: criterion validity in primary care practice. Wisc Med J
. 1995;94:135–140.Google Scholar
Gavin DR, Ross HE, Skinner HA. Diagnostic validity of the drug abuse screening test in the assessment of DSM-III
drug disorders. Br J Addict
. 1980;84:301–307.CrossRefGoogle Scholar
Rumpf H-J, Hapke H, Meyer C, John U. Screening for alcohol use disorders and at-risk drinking in the general population: psychometric performance of three questionnaires. Alcohol Alcohol
. 2002;37:261–268.PubMedGoogle Scholar
Deployment Health Clinical Center. PTSD Checklist—Military Version (PCL-M). Accessed September 3, 2004. Available at: www.pdhealth.mil/guidelines/appendix4.asp.Google Scholar
Brown RL, Leonard T, Saunders LA, Papasouliotis O. A two-item conjoint screen for alcohol and other drug problems. J Am Board Fam Pract
. 2001;14:95–106.PubMedGoogle Scholar
Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry
. 1978;33:429–435.CrossRefGoogle Scholar
Zung WW, Wonnacott TH. Treatment prediction in depression using a self-rating scale. Biol Psychiatry
. 1970;2:321–329.PubMedGoogle Scholar
Beck AT, Ward C, Mendelson M, Mock JE, Erbaugh JK. An inventory for measuring depression. Arch Gen Psychiatry
. 1961;4:561–571.PubMedGoogle Scholar
Dieperink E, Ho SB, Thuras P, Willenbring ML. A prospective study of neuropsychiatric symptoms associated with interferon-alpha-2b and ribavirin therapy for patients with chronic hepatitis C. Psychosomatics
. 2003;44:104–112.CrossRefPubMedGoogle Scholar
Wright IA. Monitoring depression in patients undergoing alpha-interferon and ribavirin therapy for hepatitis C. Gastroenterol Nurs
. 2000;23:275–280.CrossRefPubMedGoogle Scholar
Bean P. Update on new biomarkers for detecting excessive alcohol use. AlcoholMD.com Web site. November 2002. Available at: http://www.alcoholmd.com/pro/courses/biomarkers_of_alcohol_abuse.asp.Google Scholar
Wolff K, Farrell M, Marsden J. A review of biological indicators of illicit drug use: practical considerations and clinical usefulness. Addiction
. 1999;94:1279–1298.CrossRefPubMedGoogle Scholar
Portland VA Medical Center, Mood Disorders Center. Patient Screening Questions (PSQ). Accessed September 3, 2004. Available at: www.portland.me.va.gov/mood-disorders-center.Google Scholar
Martin EM, Pitrak DL, Novak RM, Pursell KJ, Mullane KM. Reaction times are faster in HIV-seropositive patients on antiretroviral therapy: a preliminary report. J Clin Exp Neuropsychol.
Hilsabeck RC, Perry W, Hassanein TI. Neuropsychological impairment in patients with chronic hepatitis C. Hepatology
. 2002;35:440–446.CrossRefPubMedGoogle Scholar
Forton DM, Thomas HC, Murphy CA, et al. Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease. Hepatology
. 2002;35:433–439.CrossRefPubMedGoogle Scholar
Ernst T, Chang L, Jovicich J, Ames N, Arnold S. Abnormal brain activation on functional MRI in cognitively asymptomatic HIV patients. Neurology
. 2002;59:1343–1349.PubMedGoogle Scholar
Martin EM, Novak RM, Fendrich M, et al. Stroop performance in drug users classified by HIV and hepatitis C virus serostatus. J Int Neurophysiol Soc.
Stephenson J. Former addicts face barriers to treatment for HCV. JAMA
. 2001;285: 1003–1005.CrossRefPubMedGoogle Scholar
Davis GL, Rodrigue JR. Treatment of chronic hepatitis C in active drug users. N Engl J Med.
Edlin BR, Seal KH, Lorvick J, et al. Is it justifiable to withhold treatment for hepatitis C from illicit-drug users. N Engl J Med.
Backmund M, Meyer K, Von Zielonka M, Eichenlaub D. Treatment of hepatitis C infection in injection drug users. Hepatology
. 2001;34:188–193.CrossRefPubMedGoogle Scholar
Ho SB, Nguyen H, Tetrick LL, Opitz GA, Basara ML, Dieperink E. Influence of psychiatric diagnoses on interferon-alpha treatment for chronic hepatitis C in a veteran population. Am J Gastroenterol.
Sylvestre DL. Treating hepatitis C in methadone maintenance patients: an interim analysis. Drug Alcohol Depend.
Dalgard O, Bjoro K, Hellum K, et al. Treatment of chronic hepatitis C in injecting drug users: 5 years’ follow-up. Eur Addict Res.
Van Thiel D, Friedlander L, Molloy P, Fagiuoli S, Kania R, Caraceni P. Interferon-alpha can be used successfully in patients with hepatitis C virus-positive chronic hepatitis who have a psychiatric illness. Eur J Gastroenterol Hepatol.
Hauser P, Khosla J, Aurora H, et al. A prospective study of the incidence and open-label treatment of interferon-induced major depressive disorder in patients with hepatitis C. Mol Psychiatry.
San Francisco and Miami Centers of excellence in Hepatitis C Research and Education and the Hepatitis C Technical Advisory Group DoVA. Treatment Recommendations for Patients With Chronic Hepatitis C
. Version 1.0. Washington, DC: Veteran’s Health Administration, Department of Veterans’ Affairs; 2002.Google Scholar
Levenson J, Fallon H. Fluoxetine treatment of depression caused by interferon-alpha. Am J Gastroenterol.
Gleason O, Yates W. Five cases of interferon-alpha-induced depression treated with antidepressant therapy. Psychosomatics
. 1999;40:510–512.PubMedGoogle Scholar
Schramm T, Lawford B, Macdonald G, Cooksley W. Sertraline treatment of interferon-alfa-induced depressive disorder. Med J Aust.
Loftis J, Socherman RE, Whitehead AJ, Hauser P. Interferon-alpha-induced depression: time course and antidepressant response of symptom dimensions for patients with hepatitis C. Psychosom Med.
In press.Google Scholar
Capuron L, Gumnick JF, Musselman DL, et al. Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology
. 2002;26:643–652.CrossRefPubMedGoogle Scholar
Pettinati HM. The use of selective serotonin reuptake inhibitors in treating alcoholic subtypes. J Clin Psychiatry
. 2001;62:26–31.PubMedGoogle Scholar
Naranjo CA, Knoke DM. The role of selective serotonin reuptake inhibitors in reducing alcohol consumption. J Clin Psychiatry
. 2001;62:18–25.PubMedGoogle Scholar
Srisurapanont M, Kittiratanapaiboon P, Jarusuraisin N. Treatment for amphetamine psychosis. Cochrane Database Syst Rev.
McLellan AT, Lewis DC, O’Brien CP, Kleber HD. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA
. 2000;284:1689–1695.CrossRefPubMedGoogle Scholar
Koob GF, Bloom FE. Cellular and molecular mechanisms of drug dependence. Science.
Wise RA, Bozarth MA. Brain substrates for reinforcement and drug self-administration. Prog Neuropsychopharmacol.
Kalivas PW, Stewart J. Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res Brain Res Rev.
Robinson TE, Berridge KC. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev.
Kreek MJ, Koob GF. Drug dependence: stress and dysregulation of brain reward pathways. Drug Alcohol Depend.
Stimmel B, Kreek MJ. Neurobiology of addictive behaviors and its relationship to methadone maintenance. Mt Sinai J Med.
Nestler EJ, Hope BT, Widnell KL. Drug addiction: a model for the molecular basis of neural plasticity. Neuron.
Capuron L, Ravaud A, Neveu PJ, Miller AH, Maes M, Dantzer R. Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry.
Bonaccorso S, Marino V, Puzella A, et al. Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system. J Clin Psychopharmacol.
Taylor MW, Feng GS. Relationship between interferon-gamma, indoleamine 2,3 dioxygenase, and tryptophan catabolism. FASEB J.
Brown RR, Ozaki Y, Datta SP, Borden EC, Sondel PM, Malone DG. Implications of interferon-induced tryptophan catabolism in cancer, auto-immune disease and AIDS. Adv Exp Med Biol.
Boyer P. Do anxiety and depression have a common pathophysiological mechanism. Acta Psychiatr Scand Suppl.
Leonard BE, Song C. Changes in the immune system in rodent models of depression. Int J Neuropsychopharmacol.
Jones TH, Wadler S, Hupart KH. Endocrine-mediated mechanisms of fatigue during treatment with interferon-alpha. Semin Oncol.
1998;25(suppl 1):54–63.PubMedGoogle Scholar
Pollak Y, Yirmiya R. Cytokine-induced changes in mood and behavior: implications for “depression due to a general medical condition,” immunotherapy and antidepressive treatment. Int J Neuropsychopharmacol.
Bonaccorso S, Puzella A, Marino V, et al. Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms. Psychiatry Res.
Foucart S, Abadie C. Interleukin-1 beta and tumor necrosis factor-alpha inhibit the release of 3
H-noradrenaline form mice isolated atria. Naunyn Schmiedebergs Arch Pharmacol.
Dunn AJ. Effects of the IL-1 receptor antagonist on the IL-1 and exotoxin-induced activation of the HPA axis and cerebral biogenic amines in mice. Neuroimmunomodulation
. 2000;7:36–45.CrossRefPubMedGoogle Scholar
Parker KJ, Schatzberg AF, Lyons DM. Neuroendocrine aspects of hypercortisolism in major depression. Horm Behav.
Spaulding A, Lau D, Weinbaum C, et al. Developing a framework for correctional management of hepatitis C. A review of current and future management of the disease in prisons. In press.Google Scholar
Drake RE, Mercer-McFadden C, Mueser KT, McHugo GJ, Bond GR. Review of integrated mental health and substance abuse treatment for patients with dual disorders. Schizophr Bull.
Druss BG, Rohrbaugh RM, Levinson CM, Rosenheck RA. Integrated medical care for patients with serious psychiatric illness: a randomized trial. Arch Gen Psychiatry.
2001; 58:861–868.CrossRefPubMedGoogle Scholar
Phillips SD, Burns BJ, Edgar ER, et al. Moving assertive community treatment into standard practice. Psychiatr Serv.
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