title: Neurobehavioral effects of interferon-α in patients with hepatitis-C: symptom dimensions and responsiveness to paroxetine.
abstract: In patients at high risk for recurrence of malignant melanoma, interferon-α (IFN-α), a stimulator of innate immunity, appears to induce distinct neurobehavioral symptom dimensions: a mood and anxiety syndrome, and a neurovegetative syndrome, of which the former is responsive to prophylactic administration of paroxetine. We sought to determine whether symptom dimensions (and treatment responsiveness) arise in patients with hepatitis C administered IFN-α and ribavirin. In a randomized, double-blind, 6-month study, 61 patients with hepatitis C eligible for therapy with IFN-α and ribavirin received the antidepressant paroxetine (n=28) or a placebo (n=33). Study medication began 2 weeks before IFN-α/ribavirin therapy. Neuropsychiatric assessments included the 10-item Montgomery-Asberg Depression Rating Scale (MADRS). The items of the MADRS were grouped into depression, anxiety, cognitive dysfunction, and neurovegetative symptom dimensions, and analyzed using a mixed model. By 2 weeks of IFN-α/ribavirin therapy, all four dimensions increased, with the symptom dimensions of anxiety and cognitive dysfunction fluctuating and worsening, respectively, in both groups over time. The depression symptom dimension was significantly lower in the paroxetine treatment group (p=0.04); severity of the neurovegetative symptom dimension was similar in both groups. Similar to patients with malignant melanoma receiving high-dose IFN-α, the depression symptom dimension is more responsive to paroxetine treatment in individuals undergoing concomitant IFN-α/ribavirin therapy. However, the anxiety, cognitive dysfunction, and neurovegetative symptom dimensions appear less responsive to prophylactic paroxetine administration. Different neurobiologic pathways may contribute to the responsiveness of IFN-α-induced symptom dimensions to antidepressant treatment, requiring relevant psychopharmacologic strategies.
authors.affiliation: Department of Psychology, University of Miami, Miami, FL, USA.
authors.forename: Marcia D
authors.initials: MD
authors.lastname: McNutt
authors.forename: Shuling
authors.initials: S
authors.lastname: Liu
authors.forename: Amita
authors.initials: A
authors.lastname: Manatunga
authors.forename: Erica B
authors.initials: EB
authors.lastname: Royster
authors.forename: Charles L
authors.initials: CL
authors.lastname: Raison
authors.forename: Bobbi J
authors.initials: BJ
authors.lastname: Woolwine
authors.forename: Marina F
authors.initials: MF
authors.lastname: Demetrashvili
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Miller
authors.forename: Dominique L
authors.initials: DL
authors.lastname: Musselman
mesh_terms: D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006526:Hepatitis C / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D017374:Paroxetine / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D012254:Ribavirin / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000998:Antiviral Agents; D016898:Interferon-alpha; D017374:Paroxetine; D012254:Ribavirin