Biphasic Pattern of Depression and Its Predictors during Pegylated Interferon-Based Therapy in Chronic Hepatitis B and C Patients

Abstract

Background

It remains unclear whether depression in chronic hepatitis B (CHB) and chronic hepatitis C (CHC) during pegylated interferon-based therapy is associated with the virus, drug or ethnic background. We aimed to perform a prospective study to evaluate the clinical course of depression and its predictors in consecutive non-cirrhotic CHB and CHC patients of the same ethnicity receiving pegylated interferon-based therapy.

Methods

The occurrence and severity of depression were actively assessed by the Hamilton Depression Rating Scale before therapy and at weeks 2, 4, 6, 8, 10, 12 and every 4 weeks during treatment until the end of therapy. Extensive numbers of variables (repeated measurements, time variables and interactions between all variables) were included in generalized estimating equations to analyse the predictors of depression.

Results

A total of 158 consecutive patients (73 CHB and 85 CHC patients) were enrolled. Depression (Hamilton Depression Rating Scale ≥11) occurred in a biphasic pattern at treatment weeks 2-10 and weeks 16-36. Treatment weeks <10 predicts more depression, and treatment weeks >12 predicts less depression, suggesting the predictability of the time variable during treatment on depression. Furthermore, CHC or pre-existing depression is an independent predictor of depression in these patients (P<0.001).

Conclusions

Depression occurred in a biphasic pattern during pegylated interferon-based therapy and should be early and actively assessed, especially in patients with CHC or pre-existing depression.

References

Lee

W.M.

Hepatitis B virus infection. N Engl J Med 1997; 337: 1733–1745.

Lauer

G.M.

, Walker

B.D.

Hepatitis C virus infection. N Engl J Med 2001; 345: 41–52.

Kao

J.H.

, Chen

D.S.

Overview of hepatitis B and C viruses. In Goedert

J.J.

(ed). Infectious Causes of Cancer: Targets for Intervention. Totowa: Humana Press Inc. 2000; pp. 313–330.

McQuillan

G.M.

, Townsend

T.R.

, Fields

H.A.

, Carrol

, Leahy

, Polk

B F.

Seroepidemiology of hepatitis B virus infection in the United States. Am J Med 1989; 87 Suppl 3A: 5S–10S.

Dan

A.A.

, Martin

L.M.

, Crone

Depression, anemia and health-related quality of life in chronic hepatitis C. J Hepatol 2006; 44: 491–498.

Guadagnino

, Trotta

M.P.

, Carioti

, Caroleo

, Antinori

Does depression symptomatology affect medication compliance during the first weeks of anti-HCV therapy in intravenous drug users?

Dig Liver Dis 2006; 38: 119–124.

Raison

C.L.

, Broadwell

S.D.

, Borisov

A.S.

Depressive symptoms and viral clearance in patients receiving interferon-alpha and ribavirin for hepatitis C. Brain Behav Immun 2005; 19: 23–27.

Maddock

, Landau

, Barry

Psychopathological symptoms during interferon-alpha and ribavirin treatment: effects on virologic response. Mol Psychiatry 2005; 10: 332–333.

Janssen

H.L.

, Brouwer

J.T.

, van der Mast

R.C.

, Schalm

S.W.

Suicide associated with alfa-interferon therapy for chronic viral hepatitis. J Hepatol 1994; 21: 241–243.

10.

Laguno

, Blanch

, Murillas

Depressive symptoms after initiation of interferon therapy in human immunodeficiency virus-infected patients with chronic hepatitis C. Antivir Ther 2004; 9: 905–909.

11.

Bagheri

, Fouladi

, Barange

Follow-up of adverse drug reactions from peginterferon alfa-2b-ribavirin therapy. Pharmacotherapy 2004; 24: 1546–1553.

12.

Capuron

, Ravaud

Prediction of the depressive effects of interferon alfa therapy by the patient's initial affective state. N Engl J Med 1999; 340: 1370.

13.

Cotler

S.J.

, Wartelle

C.F.

, Larson

A.M.

, Gretch

D.R.

, Jensen

D.M.

, Carithers

R.L.

Jr. . Pretreatment symptoms and dosing regimen predict side-effects of interferon therapy for hepatitis C. J Viral Hepat 2000; 7: 211–217.

14.

Kraus

M.R.

, Schafer

, Csef

, Faller

, Mork

, Scheurlen

Compliance with therapy in patients with chronic hepatitis C: associations with psychiatric symptoms, interpersonal problems, and mode of acquisition. Dig Dis Sci 2001; 46: 2060–2065.

15.

Raison

C.L.

, Borisov

A.S.

, Broadwell

S.D.

Depression during pegylated interferon-alpha plus ribavirin therapy: prevalence and prediction. J Clin Psychiatry 2005; 66: 41–48.

16.

Marcellin

, Lau

G.K.K.

, Zeuzem

Comparing the safety, tolerability and quality of life in patients with chronic hepatitis B vs chronic hepatitis C treated with peginterferon alpha-2a. Liver Int 2008; 28: 477–485.

17.

Koskinas

, Merkouraki

, Manesis

, Hadziyannis

Assessment of depression in patients with chronic hepatitis: effect of interferon treatment. Dig Dis 2002; 20: 284–288.

18.

Ferenci

, Staufer

Depression in chronic hepatitis: the virus, the drug, or the ethnic background?

Liver Int 2008; 28: 429–431.

19.

Hamilton

Rating depressive patients. J Clin Psychiatry 1980; 41: 21–24.

20.

Williams

J.B.W.

A structured interview guide for the Hamilton Depression Rating Scale. Arch Gen Psychiatry 1988; 45: 742–747.

21.

Huang

Y.W.

, Chayama

, Tsuge

Differential effects of interferon and lamivudine on serum HBV RNA inhibition in patients with chronic hepatitis B. Antivir Ther 2010; 15: 177–184.

22.

Kao

J.H.

, Chen

P.J.

, Lai

M.Y.

Mixed infections of hepatitis C virus as a factor in acute exacerbations of chronic type C hepatitis. J Infect Dis 1994; 170: 1128–1133.

23.

King

, Honaker

, Joseph

, Scheve

Analyzing incomplete political science data: an alternative algorithm for multiple imputation. Am Polit Sci Rev 2001; 95: 49–69.

24.

Honaker

, King

, Blackwell

Amelia Software Web Site. (Updated 21 June 2012. Accessed 1 August 2009.) Available from http://gking.harvard.edu/amelia.

25.

Lam

Normal.gee: general estimating equation for normal regression. In Imai K, King G, Lau O. Zelig: Everyone's Statistical Software. (Updated 21 June 2012. Accessed 1 August 2009.) Available from http://projects.iq.harvard.edu/zelig.

26.

Kramer

, Bauer

, Funk

Subclinical impairment of brain function in chronic hepatitis C infection. J Hepatol 2002; 37: 349–354.

27.

Forton

D.M.

, Taylor-Robinson

S.D.

, Thomas

H.C.

Cerebral dysfunction in chronic hepatitis C infection. J Viral Hepat 2003; 10: 81–86.

28.

Carta

M.G.

, Hardoy

M.C.

, Garofalo

Association of chronic hepatitis C with major depressive disorders: irrespective of interferon-alpha therapy. Clin Pract Epidemiol Ment Health 2007; 3: 22.

29.

Weinstein

A.A.

, Kallman Price

, Stepanova

Depression in patients with nonalcoholic fatty liver disease and chronic viral hepatitis B and C. Psychosomatics 2011; 52: 127–132.

30.

Kleinman

Culture and depression. N Engl J Med 2004; 351: 951–953.

31.

Raison

C.L.

, Demetrashvili

, Capuron

, Miller

A.H.

Neuropsychiatric adverse effects of interferon-alpha: recognition and management. CNS Drugs 2005; 19: 105–123.

32.

Ong

S.C.

, Mak

, Aung

M.O.

, Li

S.C.

, Lim

S.G.

Health-related quality of life in chronic hepatitis B patients. Hepatology 2008; 47: 1108–1117.

33.

Huang

Y.W.

, Hu

C.Y.

, Chen

C.L.

Human leukocyte antigen-DRB1*1101 correlates with less severe hepatitis in Taiwanese male carriers of hepatitis B virus. J Med Virol 2009; 81: 588–593.