Changes in mood states and biomarkers during peginterferon and ribavirin treatment of chronic hepatitis C.
OBJECTIVE
Depression is a frequent side effect of interferon therapy in patients with chronic hepatitis C (CHC). The aim of this study was to identify baseline and on-treatment predictors of depression in CHC patients receiving peginterferon and ribavirin.


METHODS
In total, 201 prior nonresponders with advanced fibrosis were treated with peginterferon alfa-2a and ribavirin for 24 wk in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial. Of these, 74 continued on antiviral therapy through week 48. Mood states were assessed with the Beck Depression Inventory II and the Composite International Diagnostic Interview. Plasma cortisol and whole blood serotonin levels were measured in 101 subjects at weeks 0, 4, 24, 48, and 72.


RESULTS
The incidence of interferon-induced depression was 23% and 42% at weeks 24 and 48, respectively. Although 22% of patients had baseline depression, the absence of a week 20 virological response was the only independent predictor of interferon-induced depression at week 24 (P = 0.0009). Plasma cortisol levels did not change during treatment nor correlate with depression. In contrast, whole blood serotonin/platelet levels significantly decreased during treatment, but did not correlate with interferon-induced depression through week 24 (P = 0.35), nor through week 48 (P = 0.51).


CONCLUSIONS
Depression during peginterferon and ribavirin therapy was associated with a lower antiviral response. The significant reduction in whole blood serotonin levels over time suggest that further studies of the serotonergic pathway are warranted to identify the mediators of interferon-induced depression.
Fontana
Robert J
RJ
Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA.
Kronfol
Ziad
Z
Lindsay
Karen L
KL
Bieliauskas
Linas A
LA
Padmanabhan
Latha
L
Back-Madruga
Carla
C
Lok
Anna S F
AS
Stoddard
Anne M
AM
D000339:Affect / Q000187:drug effects; D000998:Antiviral Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D003863:Depression / Q000097:blood / Q000139:chemically induced*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects*
D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a