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

Interferon-alpha (IFN-alpha) is a cytokine released early in viral infection that has both antiviral and antiproliferative activities.1 Accordingly, IFN-alpha is currently used for treatment of viral infections and certain cancers. In combination with the antiviral agent ribavirin, IFN-alpha is the only U.S. Food and Drug Administration–approved treatment of hepatitis C, which afflicts 4 to 5 million people in the United States and is the leading cause of liver failure requiring transplantation.2–4 Although a successful antiviral strategy, IFN-alpha treatment has been repeatedly shown to induce significant symptoms of depression in 20% to 50% of patients.5–9 Combined with fatigue, these symptoms represent a primary cause of poor compliance and/or treatment discontinuation.10,11 Given recent data demonstrating the seminal importance of adherence in achieving viral clearance,12 increasing attention is being paid to IFN-alpha–induced neuropsychiatric side effects as potentially manageable impediments to achieving sustained viral response during hepatitis C virus (HCV) treatment. Recent advances in the treatment of HCV include the development of pegylated preparations of IFN-alpha-2a and -2b. Pegylation extends medication half-life and appears to increase rates of sustained viral response while offering the convenience of once-per-week dosing.13,14 Recent data also suggest that pegylated interferons may be associated with decreased self-reported rates of neuropsychiatric side effects, including depression, when compared with older preparations.13–15 However, prospective evaluations of the prevalence and time course of depressive symptoms utilizing validated screening tools specific for depression during treatment with pegylated IFN-alpha have yet to be reported. Of relevance in this regard, rates of depression during therapy with non-pegylated forms of IFN-alpha have typically been higher in studies that have monitored psychiatric symptoms prospectively and have used validated assessment instruments.16 In view of the association between neuropsychiatric side effects and poor treatment outcome,7,11,15 it is important to identify factors that may increase the risk for developing depression during IFN-alpha therapy. Studies with non-pegylated preparations of IFN-alpha have indicated that the presence of depressive and/or anxiety symptoms immediately prior to IFN-alpha treatment initiation appears to play a role.7,9,17–20 In terms of risk factors inherent to treatment itself, the risk of developing depression has been found to increase with increasing dosage and duration of IFN-alpha therapy.6 Interestingly, some indirect evidence suggests that ribavirin may also contribute to depressive symptoms in patients with HCV, both alone21 and in combination with IFN-alpha.22 The present study was designed to prospectively evaluate the prevalence and severity of depressive symptoms in patients receiving pegylated IFN alpha-2b (PEG IFN) and ribavirin for the treatment of HCV. In addition, premorbid (i.e., history of depression or substance abuse) and treatment-specific (i.e., dosage of ribavirin) risk factors for the development of depression during treatment with PEG IFN plus ribavirin were examined.