To the Editor: The number of patients treated with interferon therapy has increased markedly in Japan since 1992, when the Health and Welfare Ministry approved the use of interferon for treating chronic active hepatitis C. Since then, there have been some case reports of severe depression and suicide among patients during interferon therapy. However, the incidence of depression is still not known. We report on the incidence of and risk factors for depression among hepatitis C patients receiving interferon therapy, on the basis of a prospective follow-up study.
All of the 66 patients (25 women and 41 men; mean age=49.9 years) with hepatitis C who began receiving interferon therapy at Showa University Hospital from December 1992 to December 1993 gave informed consent for participation in this study and were investigated prospectively. Recombinant interferon-alpha-2b was administered to 33, natural lymphoblastic interferon-alpha to 29, and other forms of interferon to four of these patients. Ten million units of recombinant interferon-alpha-2b or 6 million units of natural lymphoblastic interferon-alpha were given to patients intramuscularly every day for the first 2 weeks and then three times a week for the next 22 weeks. The patients were hospitalized for the first 4 weeks, with subsequent treatment at an outpatient clinic for the next 20 weeks. Psychiatric assessments were performed four times (before the treatment [at 0 weeks] and at 4, 12, and 24 weeks) by a psychiatrist (T.O.).
Interferon therapy was discontinued in three cases because of physical side effects and in four cases because of severe depression (two cases at 7 weeks, one at 9 weeks, and one at 20 weeks). The numbers of patients whose symptoms satisfied the criteria for major depressive episode in DSM-III-R were three of 66 (4.5%), 14 of 64 (21.9%), 23 of 60 (38.3%), and 16 of 59 (27.1%) at 0, 4, 12, and 24 weeks, respectively. Twenty-nine patients were not depressed before the treatment but were diagnosed with depression at least once during interferon therapy. The mean maximum Hamilton Rating Scale for Depression score among the four assessments in these 29 patients was 20.5 (SD=5.7). Two of these patients had suicidal ideation, but neither attempted suicide. Thirty-one patients completed the 6-month course of interferon therapy without experiencing depression. There were no significant differences between the groups that did and did not experience depression during interferon therapy in sex (15 men and 14 women versus 22 men and 9 women) and age (50.0 versus 49.6 years). The mean Hamilton depression scale score at week 0 was significantly higher in the 29 depressed patients (3.5) than in the 31 undepressed patients (2.0) (Wilcoxon rank sum test, p<0.05).
The depressed patients in this study were definitively diagnosed as having a psychoactive substance mood disorder, an organic mood disorder, or major depression because it is unclear whether the neurotoxicity of interferon therapy exclusively causes depression. Our findings indicate that careful monitoring for symptoms of depression in patients receiving interferon therapy is required.