title: Pegylated interferon pharmacokinetics and self-reported depressive symptoms during antiviral treatment for chronic hepatitis C.
abstract: BACKGROUND
  Pegylated interferon-2a (PegIFN-2a)+ribavirin treatment for chronic hepatitis C is often associated with depressive symptoms. Previous studies have failed to explore whether PegIFN-2a pharmacokinetic variability plays an etiologic role in PegIFN-2a-induced mood disorders. The objective of this investigation was to evaluate the association between trough PegIFN-2a concentration at treatment week 4 ("PegIFN-2a Cmin4") and an increase in depressive symptoms.
  
  
  METHODS
  Using data from Virahep-C, the association between PegIFN-2a Cmin4 and the following depression outcomes were evaluated using the Center for Epidemiological Studies-Depression scale (CES-D): (1) change in CES-D score from baseline to week 12; (2) greatest difference in CES-D score between baseline and weeks 4, 12, or 24; and (3) occurrence of severe depressive symptoms (CES-D greater than 23) at weeks 4, 12, or 24. One post-hoc analysis examined whether PegIFN-2a exposure during the first week of treatment was associated with change in CES-D score from baseline to week 4.
  
  
  RESULTS
  No significant associations between PegIFN-2a Cmin4 and the depression outcomes were observed (p>0.05). Exploratory analyses suggest a possible relationship between PegIFN-2a exposure during the first week of therapy and CES-D score change from baseline to week 4 (p=0.03).
  
  
  CONCLUSIONS
  PegIFN-2a concentration levels from baseline to week 4 do not predict the onset and severity of depressive symptoms during 24 weeks of antiviral therapy; however PegIFN-2a levels during the first week of treatment may predict depressive symptoms in the first 4 weeks, earlier than anticipated and warrants further exploration.
authors.affiliation: Division of Gastroenterology and Hepatology, UNC School of Medicine, Chapel Hill, NC, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Evon
authors.affiliation: Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Esserman
authors.affiliation: United Therapeutic Corporation, Research Triangle Park, NC, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Howell
authors.affiliation: Division of Gastroenterology and Hepatology, UNC School of Medicine, Chapel Hill, NC, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Ruffin
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects*; D019540:Area Under Curve; D003863:Depression / Q000139:chemically induced* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects*; D011569:Psychiatric Status Rating Scales; D011994:Recombinant Proteins / Q000009:adverse effects; D057566:Self Report; D012680:Sensitivity and Specificity; D013997:Time Factors; D014481:United States
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a