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Interferon-alpha-induced psychiatric side effects in patients with chronic viral hepatitis: a prospective, observational, controlled study

Published online by Cambridge University Press:  11 October 2011

M. Germana Orrù ,
Antonella Baita ,
Rossella Sitzia ,
Alessandra Costa ,
Elisabetta Muntoni ,
Sabine Landau ,
Luchino Chessa ,
M. Giulia Farci ,
Bernardo Carpiniello  and
Carmine M. Pariante
M. Germana Orrù
Affiliation:
Clinica Psichiatrica, Università degli Studi di Cagliari, Cagliari, Italy
Antonella Baita
Affiliation:
Clinica Psichiatrica, Università degli Studi di Cagliari, Cagliari, Italy
Rossella Sitzia
Affiliation:
Clinica Psichiatrica, Università degli Studi di Cagliari, Cagliari, Italy
Alessandra Costa
Affiliation:
Clinica Psichiatrica, Università degli Studi di Cagliari, Cagliari, Italy
Elisabetta Muntoni
Affiliation:
Clinica Psichiatrica, Università degli Studi di Cagliari, Cagliari, Italy
Sabine Landau
Affiliation:
Istituto di Psichiatria, King's College, London, UK
Luchino Chessa
Affiliation:
Clinica Medica, Università degli Studi di Cagliari, Cagliari, Italy
M. Giulia Farci
Affiliation:
Clinica Medica, Università degli Studi di Cagliari, Cagliari, Italy
Bernardo Carpiniello
Affiliation:
Clinica Psichiatrica, Università degli Studi di Cagliari, Cagliari, Italy
Carmine M. Pariante*
Affiliation:
Istituto di Psichiatria, King's College, London, UK
*
Address for correspondence: Dr. C.M. Pariante, Section of Clinical Neuropharmacology, PO Box 51, Institute of Psychiatry, King's College London, 1 Windsor Walk, London SES 8AF(United Kingdom). Fax: +44-20-7848.0051 E-mail: c.pariante@iop.kcl.ac.uk
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Summary

Aims — Patients with chronic viral hepatitis suffer from a high prevalence of psychiatric problems. Furthermore, the treatment for chronic viral hepatitis, with interferon (IFN) alpha, induces the occurrence of further psychopathological symptoms. The autors examined whether patients with a pre-existing psychiatric diagnosis had more severe IFN alpha-induced psychiatric adverse effects, and whether they were more likely to interrupt the IFN alpha therapy, compared with control patients with no pre-existing psychiatric diagnosis. They also examined the psychopharmacological management of the interferon-alpha-induced psychiatric side effects. Methods — The authors studied prospectively 60 patients with chronic hepatitis B or C in Cagliari, Italy. Patients underwent psychiatric assessment before starting interferon alpha and monthly throughout the therapy. Results — After adjusting for the baseline psychopathology, there was no statistically significant difference in interferon-alpha-induced psychiatric adverse effects between patients with a pre-existing psychiatric diagnosis and controls. There was also no evidence that psychiatric cases were more likely than controls to interrupt the IFN alpha therapy because of psychiatric side effects. Moreover, there was no difference in the psychiatric adverse effects severe enough to require psychopharmacological treatment. Finally, psychopharmaco-logical management successfully treated psychiatric symptoms induced by the IFN alpha. Conclusions — Patients with a pre-existing psychiatric diagnosis do not have a specific vulnerability to interferon-alpha-induced psychiatric adverse effects.

Declaration of Interest: none of the authors have conflict of interests in writing this paper; CM. Pariante is funded by the UK Medical Research Council and by the NARSAD and the Guy's and St Thomas Charity

Keywords

interferon-alphahepatitisdepressionanxiety
Type
Original Papers
Information
Epidemiology and Psychiatric Sciences , Volume 14 , Issue 3 , September 2005 , pp. 145 - 153
Copyright
Copyright © Cambridge University Press 2005

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References

BIBLIOGRAFIA

American Psychiatric Association (1987). Diagnostic and Statistical Manual of Mental Disorders, (3rd ed. revised). American Psychiatric Press: Washington DC.Google Scholar
Beck, A.T., Ward, C.H., Mendelson, M., Mock, J. & Erbaugh, J. (1961). An inventory for measuring depression. Archives of General Psychiatry 5, 561–571.CrossRefGoogle Scholar
Bonkovsky, H.L., Woolley, J.M. & The Consensus Interferon Group (1999). Reduction of health-related quality of life in chronic hepatitis C and improvement with interferon therapy. Hepatologx 29, 264–270.CrossRefGoogle ScholarPubMed
Byrne, G., Lehman, L., Kirshbaum, J., Borden, E., Lee, C. & Brown, R. (1986). Induction of tryptophan degradation in vitro and in vivo: a gamma interferon stimulated activity. Journal of Interferon hserach 6, 389–396.CrossRefGoogle ScholarPubMed
Capuron, L. & Ravaud, A. (1999). Prediction of the depressive effects of interferon-alpha-therapy by the patient's initial affective state. New England Journal of Medicine 340, 1370.CrossRefGoogle Scholar
Capuron, L., Ravaud, A., Neveu, P.J., Miller, A.H., Maes, M. & Dantzer, R. (2002). Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Molecular Psychiatry 7, 468–473.CrossRefGoogle ScholarPubMed
Carpiniello, B., Orru, M.G., Baita, A., Pariante, C.M. & Farci, A.M.G. (1998). Mania induced by withdrawal ot treatment with Interferon Alfa. Archives of General Psychiatry 55, 88–89.CrossRefGoogle Scholar
Cassidy, E.M. & O'Keane, V. (2000). Depression and interferon alpha therapy. British Journal of Psychiatry 176, 494.CrossRefGoogle ScholarPubMed
Dieperink, E., Willenbring, M. & Ho, S.B. (2000). Neuropsychiatric symptoms associated with hepatitis c and interferon-alpha: a review. American Journal of Psychiatry 157, 867–876.CrossRefGoogle ScholarPubMed
Dieperink, E., Ho, S.B., Tetrick, L., Dua, K. & Willenbring, M.L. (2004). Suicidal ideation during interferon-alpha 2b and ribavirin treatment of patients with chronic hepatitis C. General Hospital Psychiatry 26(3), 237.CrossRefGoogle ScholarPubMed
Esteban, R. (1996). Managing patients on inteferon therapy. Digestive Disease and Science 41, 121S–125S.CrossRefGoogle Scholar
Fava, M., Guaraldi, G.P. & Mazzi, F. (1993). SCID: Intervista Clinica Strutturata per il DSM-III-R. Versione italiana. OS: Firenze [Spitzer R.L., Williams J.B., Gibbon M., First M.B. (1992). The Structured Clinical Interview for DSM-III-R (SCID). History, rationale and description. Archives of General Psychiatry 49, 624-629].Google Scholar
Gleason, O.C. & Yiates, W.R. (1999). Five cases of interferon alpha-induced depression treated with antidepressant therapy. Psvchosomatics 40, 510–512.CrossRefGoogle ScholarPubMed
Gleason, O.C., Yates, W.R., Isbell, M.D. & Philipsen, M.A. (2002). An open-label trial of citalopram for major depression in patients with hepatitis C. Journal of Clinical Psychiatry 63(3), 194–198.CrossRefGoogle ScholarPubMed
Goulding, C., O'Connell, P. & Murray, F.E. (2001). Prevalence of fibromyalgia anxiey and depression in chronic hepatitis C virus infection: relationship to RT-PCR status and mode of acquisition. European Journal Gastroenterology and Hepatology 13, 507–511.CrossRefGoogle Scholar
Guy, W. (1976). ECDEU Assessment Manual for Psychopharmacology. US Dept. of Health, Education and Welfare: Bethesda MD.Google Scholar
Hamilton, M. (1960). A rating scale for depression. Neurosurgery and Psychiatry 23, 56–62.CrossRefGoogle ScholarPubMed
Hauser, P. (2004). Neuropsychiatric side effects of HCV therapy and their treatment: focus on IFN-alpha-induced depression. Gastroenterolgy Clinics of North America 33, Suppl. 1, S35–50.Google ScholarPubMed
Hauser, P., Soler, R., Reed, S., Kane, R., Gulati, M., Khosla, J., Kling, M.A., Valentine, A.D. & Meyers, C.A. (2000). Prophilactic treatment of depression induced by interfeon-alpha. Psvchosomatics 41, 439–441.CrossRefGoogle Scholar
Hauser, P., Khosla, J., Aurora, H., Laurin, J., Kling, M.A., Hill, J., Gulati, M., Thornton, A.L., Scultz, R.L., Valentine, A.D., Meyers, C.A. & Howell, C.D. (2002). A prospective study of the incidence and open-label treatment of interferon-induced major depressive disorders in patients with hepatitis. Clinical Molecular Psychiatry 7, 942–947.CrossRefGoogle ScholarPubMed
Hensley, M.L., Peterson, B., Silver, R.T., Larson, R.A., Schiffer, C.A. & Szatrowsky, T.P. (2000). Risk factors for severe neuropsychiatric toxicity in patients receiving interferon alpha-2b and low dose cylarabine for chronic myelogenous leukemia: analysis of cancer and leukmia group B 9013. Journal of Clinical Oncology 18, 1301–1308.CrossRefGoogle Scholar
Ho, S.B., Nguyen, H., Tetrick, L.L., Opitz, G.A., Basara, M.L. & Dieperink, E. (2001). Influence of psychiatric diagnosis on interferon-alpha treatment of chronic hepatitis C in a veteran population. American Journal of Gastroenterologv 96, 157–164.Google Scholar
Kraus, M.R., Schafer, A., Csef, H. & Scheurlen, M. (2002) Paroxetine for the treatment of interferon alpha induced depression in chronic hepatitis C. Alimentary Pharmacology and Therapeutics 16, 1091–1099.CrossRefGoogle ScholarPubMed
Levenson, J.L. & Fallon, H.J. (1993). A treatment of depression caused by interferon-alpha. American Journal of Gaslroenterologx 88, 760–761.Google ScholarPubMed
Loftis, J.M., Socherman, R.E., Howell, C.D., Whitehead, A.J., Hill, J.A., Dominitz, J.A. & Hauser, P. (2004). Association of interferon-alpha-induced depression and improved treatment response in patients with hepatitis C. Neuroscience Letter 365(2), 87–91.CrossRefGoogle ScholarPubMed
Mac Donald, E.M., Mann, A.H. & Thomas, H.C. (1987). Interferons as mediators of psychiatric morbidity. An investigation in a trial of recombinant alpha-interferon in hepatitis-B-carriers. Lancet 2, 1175–1177.Google Scholar
Maddock, C. & Pariante, C.M. (2001). How does stress affect you? An overview of stress, immunity, depression and disease. Epidemiologia e Psichiatria Sociale 10(3), 153–162.CrossRefGoogle Scholar
Maddock, C., Baita, A., Orrii, M.G., Sitzia, R., Costa, A., Muntoni, E., Farci, M.G., Carpiniello, B. & Pariante, C.M. (2004). Psychopharmacological treatment of depression, anxiety, irritability and insomnia in patients receiving interferon alfa: a prospective case series and a discussion of biological mechanisms. Journal of Psychopharmacology 18(1), 41–46.CrossRefGoogle Scholar
Maddock, C., Landau, S., Barry, K., Maulayah, P., Hotopf, M., Cleare, A., Norris, S. & Pariante, C.M. (in press). Psychopathological symptoms during interferon- and ribavirin treatment: effects on virologic response. Molecular Psychiatry.Google Scholar
Malek-Ahmadi, P. & Ghandour, E. (2004). Bupropion for treatment of interferon-induced depression. Annals of Pharmacotherapy 38(7-8), 1202–1205.CrossRefGoogle ScholarPubMed
Menkes, D.B. & Mac Donald, J.A. (2000). Interferons, serotonin and neurotoxicity. Psychological Medicine 30, 259–268.CrossRefGoogle ScholarPubMed
Meyers, C.A. & Valentine, A.D. (1995) Neurological and psychiatric adverse effects of immunological therapy. CNS Drugs 3, 56–68.CrossRefGoogle Scholar
Miller, A.H., Pariante, C.M. & Pearce, B.D. (1999). Effects of cytokines and glucocorticoid receptor expression and function: glucocorticoid resistance and relevance to depression. In Cytokines, Stress and Depression, (ed. Dantzer, R et al.), Kluwer Academic/plenum Plubishers: New YorkGoogle Scholar
Montgomery, S.A. (2002). Dopaminergic deficit and the role of amisulpiride in the treatment of mood disorders. International Clinical Psychopharmacology 17, Suppl 4, S9–15.Google Scholar
Mulder, R., Ang, M., Chapman, B., Ross, A., Stevens, I.F. & Edagar, C. (2000). Interferon treatment is not associated with a worsening of psychiatric symptoms in patients with hepatitis C. Journal of Gastroenterologv and Hepatology 15, 300–303.CrossRefGoogle Scholar
Musselman, D.L., Lawson, D.H., Gumnick, S.F., Manatunga, A.K., Penna, S., Goodkin, R.S., Greiner, K., Nemeroff, C.B. & Miller, A.H. (2001). Paroxetine for the prevention of depression induced by high-dose interferon alpha. New England Journal of Medicine 344, 961–966.CrossRefGoogle Scholar
Myiaoka, H., Otsubo, T.Kamijima, K., Ishii, M., Onuki, M. & Mitamura, K. (1999) Depression from interferon therapy in patients with hepatitis C. American Journal of Psychiatry 156, 1120.CrossRefGoogle Scholar
Nagano, J., Nagasi, S., Sudo, N. & Kubo, C. (2004). Psychosocial stress, personality and the severity of chronic hepatitis C. Psxchosomatics 45(2), 100–106.CrossRefGoogle ScholarPubMed
Nozaki, O., Tkagi, C., Takaoka, K., Takata, T. & Yoshida, M. (1997). Psychiatric manifestations accompanying interferon therapy for patients with chronic hepatitis C: an overview of cases in Japan. Psychiatry and Clinical Neurosciences 51, 175–180.CrossRefGoogle ScholarPubMed
Pariante, C.M., Orru, M.G., Baita, A., Farci, M.G. & Carpiniello, B. (1999a). Treatment with IFN alfa in patients with Chronic Hepatitis and mood or anxiety disorders. Lancet 354, 131–132.CrossRefGoogle ScholarPubMed
Pariante, C.M., Pearce, B.D., Pisell, T.L., Sanchez, C.I., Po, C., Su, C. & Miller, A.H. (1999b). The pro-inflammatory cytokine, interleukin-1 alpha, reduces glucocorticoid receptor translocation and function. Endocrinology 140, 4359–4366.CrossRefGoogle Scholar
Pariante, C.M., Landau, S. & Carpiniello, B. (2002). Interferon alpha-induced neuropsychiatric adverse effect in patients with psychiatric diagnosis: a prospective, controlled study. New England Journal of Medicine 347(2), 148–149.CrossRefGoogle Scholar
Poynard, T., Leroy, V., Cohard, M., Thevenot, T., Mathurin, P., Opolon, P. & Zaesky, J.P. (1996). Meta analysis of interferon randomized trials in the treatment of viral hepatitis C: effects of dose and duration. Hepatology 24, 778–789.CrossRefGoogle ScholarPubMed
Renault, P.F., Hoofnagle, J.H., Park, Y., Mullen, K.D., Peters, M. & Jones, E.A. (1987). Psychiatric complications of long-term interferon alpha therapy. Archives of Internal Medicine 147, 1577–1580.CrossRefGoogle Scholar
Russo, S., Boon, J.C., Korf, J. & Haagsma, E.B. (2003). Mirtazapine for the treatment of interferon-induced psychopathology. General Hospital Psychiatry 25(6), 497.CrossRefGoogle ScholarPubMed
Schramm, T.M., Lawford, B.R., Mac Donald, G.A. & Cooksly, W.G. (2000). Sertraline treatment of ifn-alpha induced depressive disorders. Medical Journal of Australia 173, 359–361.CrossRefGoogle Scholar
Spielberg, C.D., Gorsuch, R.L. & Lushene, R.E. (1968). State-Trait Anxiety Inventory, Eorm X. Consulting Psychologist Press: Palo Alto.Google Scholar
Valentine, A.D., Meyers, C.A., Kling, M.A., Richelson, E. & Hauser, P. (1998). Mood and cognitive side effects of interferon-alpha therapy. Seminars in Oncology 25, Suppl 1, 39–47.Google ScholarPubMed
Van Thiel, D.H., Friedlander, L., Molloy, P.J., Fagiuoli, S., Kania, R.J. & Caraceni, P. (1995). Interferon-alpha can be used successfully in patients with hepatitis C virus-positive chronic hepatitis who have a psychiatric illness. European Journal of Gastroenterology and Hepatology 7, 165–168.Google ScholarPubMed
Wessely, S. & Pariante, C.M. (2002). Fatigue, depression and chronic hepatitis C infection. Psychological Medicine 32, 1–10.CrossRefGoogle ScholarPubMed
Woo, M.H. & Burnakis, T.G. (1997). Interferon alfa in the treatment of chronic viral hepatitis B and C. Annals of Pharmacotherapy 31, 330–337.CrossRefGoogle ScholarPubMed