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

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 with increased likelihood of developing 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.

Figure 1

Depression Scores (A) and Percentage of Patients Experiencing Moderate to Severe Depressive Symptoms (B) Among Patients With HCV Receiving PEG IFN/Ribavirin Therapy^{a a} Depressive symptoms were assessed using the SDS. Numbers of paitents included at each assessment point were as follows: baseline. N = 162; week 4, N = 162; week 8, N = 156; week 12, N = 150; week 24, N = 140. * Signifiicantly different from beseline (p < .05). † Significantly different from other time points (p < .05). Abbreviations: HCV-hepatites C virus, PEG IFN = pegylated interferon alpha-2b. SDS = Zung Self-Rating Depression Scale.

Figure 2

Relationship Between Baseline and Maximum Depression Scores During PEG IFN/Ribavirin Treatment in 162 Patients With HCV^{a a} Depressive symptoms were assessed using the SDS. The baseline depression score for each patient was plotted along with the maximum depression score reached at any point during PEG IFN/ribavirin therapy. Linear regression analysis revealed a significant linear relationship (Y = 0.55X + 32.7, p < .0001) between baseline (X) and minimum (Y) depression scores that allowed prediction of severity of depressive symptoms during PEG IFN\ribavirin therapy based on the baseline depression score. Abbreviations; HCV = hepatitis C virus, PEG IFN = pegylated interferon alpha-2b, SDS = Zung Self-Rating Depression Scale.