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Pharmacopsychiatry 2014; 47(06): 195-201
DOI: 10.1055/s-0034-1385929
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Pegylated Interferon Pharmacokinetics and Self-Reported Depressive Symptoms During Antiviral Treatment for Chronic Hepatitis C

D. M. Evon
1   Division of Gastroenterology and Hepatology, UNC School of Medicine, Chapel Hill, NC, USA
,
D. E. Esserman
2   Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA
,
M. A. Howell
3   United Therapeutic Corporation, Research Triangle Park, NC, USA
,
R. A. Ruffin
1   Division of Gastroenterology and Hepatology, UNC School of Medicine, Chapel Hill, NC, USA
4   Currently at Durham Veterans Affairs Medical Center, Durham, NC, USA
› Author Affiliations
Further Information

Publication History

received 17 December 2013
revised 16 June 2014

accepted 15 July 2014

Publication Date:
14 August 2014 (online)

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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.

Key words

depression - pharmacokinetics - liver disease patients - hepatitis C - interferon
 

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