Neurobehavioral effects of interferon-α in patients with hepatitis-C

Symptom dimensions and responsiveness to paroxetine

Marcia D. McNutt, Shuling Liu, Amita Manatunga, Erica B. Royster, Charles L Raison, Bobbi J. Woolwine, Marina F. Demetrashvili, Andrew H. Miller, Dominique L. Musselman

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1444-1454
Number of pages11
JournalNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Volume37
Issue number6
DOIs
StatePublished - May 2012
Externally publishedYes

Fingerprint

Paroxetine
Hepatitis C
Interferons
Ribavirin
Depression
Anxiety
Therapeutics
Antidepressive Agents
Melanoma
Innate Immunity
Placebos
Recurrence

Keywords

  • depressive
  • hepatitis C
  • interferon-a
  • neurovegetative
  • paroxetine
  • ribavirin

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Neurobehavioral effects of interferon-α in patients with hepatitis-C : Symptom dimensions and responsiveness to paroxetine. / McNutt, Marcia D.; Liu, Shuling; Manatunga, Amita; Royster, Erica B.; Raison, Charles L; Woolwine, Bobbi J.; Demetrashvili, Marina F.; Miller, Andrew H.; Musselman, Dominique L.

In: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, Vol. 37, No. 6, 05.2012, p. 1444-1454.

Research output: Contribution to journalArticle

McNutt, Marcia D. ; Liu, Shuling ; Manatunga, Amita ; Royster, Erica B. ; Raison, Charles L ; Woolwine, Bobbi J. ; Demetrashvili, Marina F. ; Miller, Andrew H. ; Musselman, Dominique L. / Neurobehavioral effects of interferon-α in patients with hepatitis-C : Symptom dimensions and responsiveness to paroxetine. In: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2012 ; Vol. 37, No. 6. pp. 1444-1454.
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