Treatment for drug-induced depression usually consists of cessation or reduction of the causative agent and psychopharmacologic management. In addition, psychotherapy can be useful as an adjunctive treatment. The author presents case material related to a young woman with an inborn physical illness, who became depressed during the course of interferon treatment for a medical complication, hepatitis virus infection. In addition to the cessation of interferon and pharmacologic management, supportive psychotherapy of a psychodynamic orientation was started in order to address the patient’s low self-esteem and anxiety about her future. During the course of psychotherapy, it was understood that the premature cessation of interferon was, to her, a narcissistic injury. It was also important to explore the meanings of her inborn illness and her guilty feelings. After reviewing various formulations of depression, the author discusses the case material from an integrative perspective, which describes vicious cycles of depression.