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Depression during pegylated IFN-alpha plus ribavirin therapy: prevalence and prediction.

Raison CL, Borisov AS, Broadwell SD, Capuron L, Woolwine BJ, Jacobson IM, Nemeroff CB, Miller AH.
Depression during pegylated IFN-alpha plus ribavirin therapy: prevalence and prediction.
Journal of Clinical Psychiatry 2005;66:41-48.

Summary

This is a report from one of several 'modeling' studies conducted by the CDC CFS collaborative research group. Perturbations of the immune system likely play a role in the pathophysiology of CFS but studies to date have been complicated by patient heterogeneity with respect to chronicity and co-morbid illnesses. 'Model' systems, in which symptom-free subjects develop CFS-like illness following exposure to a known immune system stimulus, obviate these problems and permit controlled studies of the pathophysiology of fatigue and associated symptoms as they relate to immune and endocrine activation. Interferon-alpha (IFN-alpha), a cytokine used in the treatment of hepatitis C, activates the immune system and produces an illness resembling CFS (e.g., fatigue, cognitive complaints, pain, sleep disturbance, and depression) and we are using this to help understand the symptoms and pathophysiology of CFS. This particular publication documents that depression occurs along with other symptoms of CFS following immune activation. The occurrence of depression was primarily predicted by prior depression.

Abstract

Background: Interferon-alpha (IFN-alpha) plus ribavirin is used to treat hepatitis C virus (HCV) infection and is associated with a high rate of depression. Newer, pegylated preparations of IFN-alpha have a longer half-life, require once-per-week dosing, and may be associated with reduced neuropsychiatric burden. Limited data exist on depression during pegylated IFN-alpha therapy.

Method: Depressive symptoms were assessed using the Zung Self-Rating Depression Scale (SDS) in 162 HCV-infected patients at baseline and after 4, 8, 12, and 24 weeks of treatment with pegylated IFN alpha-2b (PEG IFN) plus weight-based (N = 86) versus standard dose (N = 76) ribavirin. Data were collected from March 2001 to April 2003. RESULTS: Compared with baseline, mean SDS index scores were significantly increased by week 4 and remained elevated throughout the study. Thirty-nine percent of the sample experienced moderate to severe depressive symptoms (SDS index score > or = 60) at some point during PEG IFN/ribavirin therapy. Baseline depression scores significantly predicted severity of depressive symptoms during PEG IFN/ribavirin treatment (simple regression analysis: Y = 0.55X + 32.7, p < .0001). In addition, assignment to weight-based ribavirin treatment and history of depression were associated oping moderate to severe depressive symptoms (odds ratio [OR] = 2.7, 95% CI = 1.3 to 5.6, p < .01, and OR = 3.3, 95% CI = 1.3 to 8.1, p < .01, respectively).

Conclusions: Development of moderate to severe depressive symptoms occurred frequently during PEG IFN/ribavirin treatment and was predicted by baseline depression scores and higher doses of ribavirin. History of major depressive disorder was also a significant predictive factor, but only through association with elevated baseline depression status. All of these factors can be evaluated and addressed to limit neuropsychiatric morbidity during HCV treatment.

Page last modified on May 8, 2006

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