Michael R. Kraus

Psychiatric side effects of interferon alfa are frequently observed in the therapy of patients with chronic hepatitis C infection. The goal of the present study was to assess prospectively the incidence, spectrum, and extent of psychiatric symptoms of patients receiving interferon alfa therapy as compared with an untreated reference group. 104 patients with chronic hepatitis C were consecutively enrolled in a prospective longitudinal study. The treatment group (N = 84) received interferon alfa-2b for up to 12 months, and the reference group (N = 20) received no treatment. Patients who began treatment between November 1996 and August 1998 (N = 44) received interferon alfa-2b, 5 million units 3 times per week. Patients who began treatment in September 1998 or later (N = 40) received a combination of interferon alfa-2b, 3 to 5 million units 3 times per week, and ribavirin, 1000-1200 mg/day. Diagnostic scores for depression and anxiety were obtained by means of the psychometric instrument Hospital Anxiety and Depression Scale, and scores for anger/hostility were obtained with the Symptom Checklist-90 Revised. In contrast to the untreated reference group, we found significantly increased scores for depression (p <.001) and anger/hostility (p <.001) during interferon alfa therapy in the treatment group. Even before therapy, scores of those in the treatment group were above the respective cutoff values for clinically relevant symptoms of depression in 15.5% of the patients, anxiety in 13.1% of the patients, and anger/hostility in 11.3% of the patients. These proportions rose to 35.0% (depression), 25.6% (anxiety), and 24.5% (anger/hostility). The cumulative frequency of clinically relevant emotional distress (depression, anxiety, or anger/hostility) during interferon alfa therapy was 57.7%, as compared with 22.5% before therapy. However, interferon alfa therapy had to be stopped prematurely because of untreatable psychiatric symptoms in only 8.3% of patients. In view of the high frequency and extent of psychiatric symptoms with interferon alfa therapy, we recommend a close follow-up of patients receiving this therapy with respect to potential limiting mood changes.

Summary: Background : Psychiatric side‐effects may require dose reduction or premature discontinuation of interferon therapy in chronic hepatitis C. New strategies are needed in order to prevent the premature termination of interferon therapy.Aim : To evaluate prospectively the efficacy and tolerability of antidepressant therapy (paroxetine, a selective serotonin reuptake inhibitor) in patients with chronic hepatitis C treated with interferon‐α who have developed interferon‐induced major depression.Methods : A sub‐group of 14 individuals from 121 consecutively treated hepatitis C patients developed substance‐induced major depression without suicidal ideation during interferon‐α treatment. The individuals in this sub‐group received paroxetine after the occurrence of depression (20 mg daily until termination of interferon therapy). Diagnostic scores for depression (and anger–hostility) were obtained in a repeated measures design (Hospital Anxiety and Depression Scale and Symptom Checklist 90 Items Revised).Results : Eleven of the 14 patients (78.6%) with interferon‐induced major depression were able to complete interferon‐α therapy as scheduled under concomitant paroxetine treatment (three dropouts: insufficient improvement of depression, occurrence of epileptic seizures, paroxetine‐induced nausea/dizziness). Within 4 weeks after the start of paroxetine medication, depression scores declined significantly in all patients.Conclusions : Our data suggest that concomitant therapy with paroxetine is an effective way to treat interferon‐induced depression in patients with chronic hepatitis C.