104 Psychosomatics 44:2, March-April 2003 A Prospective Study of Neuropsychiatric Symptoms Associated With Interferon- -2b and Ribavirin Therapy for Patients With Chronic Hepatitis C ERIC DIEPERINK, M.D., SAMUEL B. HO, M.D. PAUL THURAS,PH.D., MARK L. WILLENBRING, M.D. The purpose of this study was to systematically describe the neuropsychiatric side effects of treat- ment with interferon--2b (INF-) and ribavirin in patients with chronic hepatitis C as well as to compare different instruments used to measure these side effects. Fifty-five patients with chronic hepatitis C were prospectively followed for 24 weeks and assessed with seven neuropsychiatric symptom measures and one quality of life scale. Of 42 patients treated with INF- and ribavirin, 11 (26%) were receiving psychiatric treatment at baseline. They scored higher on all rating scales at baseline and became more symptomatic during treatment. Of the 31 patients (74%) not in psychiatric care at baseline, 15 (48%) required treatment for neuropsychiatric symptoms, and seven (23%) met criteria for major depression during INF- therapy. The control group of 13 untreated subjects showed little change over the 24-week period. All symptom scales were highly intercorrelated, suggesting that use of one is sufficient for monitoring symptoms. (Psychosomatics 2003; 44:104–112) Received April 18, 2002; accepted Aug. 5, 2002. From the Veterans Affairs Medical Center, Minneapolis; and the Departments of Psychi- atry and Medicine, University of Minnesota, Minneapolis. Address re- print requests to Dr. Willenbring, Department of Psychiatry (116A), VA Medical Center, One Veterans Dr., Minneapolis, MN 55417; Mark.Willenbring@med.va.gov (e-mail). Copyright  2003 The Academy of Psychosomatic Medicine. C hronic infection with the hepatitis C virus is one of the most common causes of advanced liver disease. The number of patients with cirrhosis, liver failure, and hepatocellular carcinoma due to chronic hepatitis C is in- creasing, and currently chronic hepatitis C is the leading indication for liver transplantation. 1–3 Treatments utilizing interferon--2b (INF-) have the potential to alter the course of chronic hepatitis C and prevent complications. 4,5 Recent advances in therapy with pegylated INF- have sig- nificantly improved treatment outcome. 6 Unfortunately, many severely ill patients are not receiving INF- because of concerns regarding neuropsychiatric side effects. 7 Depression is commonly observed in patients receiv- ing INF-, and suicides have occurred. 8,9 Published reports indicate that 15%–40% of patients develop depressive symptoms during therapy. 7 However, the incidence, time course, severity, need for psychiatric intervention, and pre- dictive factors for depressive symptoms have not been sys- tematically described. Previous studies have used various symptom scales administered at different time points, mak- ing results difficult to compare. Patients with histories of psychiatric and substance use disorders are frequently ex- cluded from INF- treatment, 10 so little is known about their neuropsychiatric symptom response and tolerance of treatment. Furthermore, it is not clear how best to monitor or screen for neuropsychiatric symptoms in patients treated with INF-, nor has an optimal treatment approach been determined. A particularly important question is whether all patients should be treated with antidepressants or whether treatment should be symptom based. Answering