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Depressive symptoms and viral clearance in patients receiving interferon-α and ribavirin for hepatitis C.

Raison CL, Broadwell SD, Borisov AS, Manatunga AK, Capuron L, Woolwine BJ, Jacobson IM, Nemeroff CB, Miller AH
Depressive symptoms and viral clearance in patients receiving interferon-α and ribavirin for hepatitis C
Brain, Behavior, and Immunity 2005;19:23-27 The complete electronic version of this article is available via the Digital Object Identifier System (DOI) at doi:10.1016/j.bbi.2004.05.001

Summary

This is a report from one of the 'modeling' studies conducted by the CDC CFS collaborative research group. Modeling studies conducted collaboratively with research group investigators from Emory University measure immune and neuroendocrine parameters and sleep, metabolism, mood, and cognitive responses to interferon (IFN)-α therapy for hepatitis C virus (HCV). IFN-α is a powerful immune modulator, and patients who receive IFN-α develop a CFS-like illness. Insights gained from studies of IFN-α have helped us to interpret results from field studies of CFS. In this study, we found that the degree of fatigue and associated depression resulting from IFN-α treatment of HCV was a predictive outcome of the virus' response to treatment: patients who developed the most severe depression and associated fatigue due to interferon-α were least likely to clear the virus. This suggests that fatigue and depression during IFN-α therapy may be a manifestation of a physiologic response associated with an impaired immune response.

Abstract

Interferon (IFN)-α plus ribavirin is an effective treatment for hepatitis C virus (HCV) infection, but is associated with a high rate of depression. Depression has been linked to a worse outcome in multiple medical disorders including viral illnesses. We examined whether increased symptoms of depression during IFN-α/ribavirin therapy were associated with a reduced treatment response as assessed by clearance of HCV. Depressive symptoms were evaluated in 102 HCV-infected patients at baseline and after 4, 8, 12, and 24 weeks of pegylated IFN-α-2b plus ribavirin therapy using the Zung self-rating depression scale (SDS). Viral clearance was determined at 24 weeks by polymerase chain reaction (PCR). Only 34% of subjects (10 out of 29) with a 20-point or greater increase in SDS Index score were HCV PCR negative at 24 weeks, compared to 59% (24 out of 41) of patients with a 10-19 point increase in SDS Index and 69% (22 out of 32) of patients with a less than 10 point increase (χ2=7.6, df=2, p<0.05). In addition, a 20-point or greater increase in SDS Index score during IFN-α/ribavirin therapy significantly predicted failure to clear virus when considered alone (crude odds ratio 3.2; 95% confidence interval 1.3-8.0; p<0:01) or when controlling for other factors that affected IFN-α treatment response (adjusted OR, 3.6; 95% CI, 1.3-9.5; p=0.01). These preliminary findings suggest that individuals who experience significant increases in depressive symptoms during IFN-α/ribavirin therapy may be less likely to clear virus, highlighting the importance of identifying and treating depressive symptoms in this patient population.

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