Mood alterations during interferon-alfa therapy in patients with chronic hepatitis C: Evidence for an overlap between manic/hypomanic and depressive symptoms

Background: Psychiatric side effects are common during interferon-alfa (IFN-alfa) therapy and often responsible for early treatment discontinuation, thus limiting its therapeutic potential. Depression is considered the hallmark of these side effects. However, irritability, anger/hostility, and manic/hypomanic episodes have also been reported, suggesting that these symptoms are important features of IFN-alfa-induced neuropsychiatric side effects. Objective: The aim of this prospective study was to use item-by-item analysis to thoroughly characterize neuropsychiatric symptoms occurring during early IFN-alfa therapy in a large cohort of patients with chronic hepatitis C. Method: Ninety-three previously IFN-alfa-naive patients treated with pegylated IFN-alfa plus ribavirin for chronic hepatitis C were studied. Neuropsychiatric assessments were conducted before initiation and after weeks 4 and 12 of antiviral therapy. They included the Mini-International Neuropsychiatric Interview, the 10-item Montgomery-Asberg Depression Rating Scale, the State-Trait Anxiety Inventory, and the Brief Fatigue Inventory. Results: Psychiatric events occurred in 30 patients (32%). They consisted of mood disorders in all cases: mania in 3 cases (10%), irritable hypomania in 15 cases (50%), and depressive mixed states in 12 cases (40%). Neurovegetative symptoms appeared within 4 weeks in most patients. In patients who developed mood disorders, sadness and depressive thoughts were present but minimal in severity. In contrast, inner tension and anxiety symptoms increased significantly over time only in these patients. Conclusions: Our results suggest that IFN-alfa-induced mood disorders are common and consist of an overlap between depressive and manic symptoms rather than a mere depression. The impact of such findings on therapeutic management should be investigated.