Interferon-alpha-induced depression: Comparisons between early- and late-onset subgroups and with patients with major depressive disorder

Interferon (IFN)-alpha, until recently the standard treatment of hepatitis C virus (HCV) infection, is associated with a significant risk of major depressive episode (MDE, or IFN-alpha-induced depression). However, it is little studied the comparisons of clinical manifestations between IFN-alpha-induced depression and major depressive disorder (MDD). In addition, IFN-alpha induces different neuroinflammation and neuroendocrine status throughput the HCV treatment course; however, the clinical presentations have never been compared between early-onset and later-onset IFN-alpha-induced depression. We assessed 200 HCV patients starting IFN-alpha therapy bi-weekly for 24 weeks, with the structured interview for confirmation of diagnosis of IFN-alpha-induced depression and with clinical rating scales for depressive symptoms and neuropsychiatric symptoms. Subjects developed IFN-alpha-induced depression (n = 59, 30%) during the first 6 weeks of IFN-alpha therapy were defined as the early-onset group (n = 32), while those developed depression after the 6th week were defined as the late-onset group (n = 27). A matched group of MDD patients (n = 60) was used to compare specific clusters of depressive symptoms with early- and late-onset IFN-alpha-induced depression. Compared to the matched group of MDD patients, IFN-alpha-induced depression was significantly associated with more somatic symptoms and fewer symptoms of mood, anxiety and negative cognition. More somatic symptoms were also found in those who became clinically depressed at early stage of IFN-alpha therapy. We suggest that the specific somatic features of interferon-alpha-induced depression, and especially of early-onset depression, characterise individuals who are more sensitive to cytokines-induced changes in mood.