No increase in depression with low-dose maintenance peginterferon in prior non-responders with chronic hepatitis C.
BACKGROUND
Peginterferon and ribavirin treatment of chronic hepatitis C (CHC) is frequently associated with dose-limiting neuropsychiatric toxicity. The purpose of this study is to determine whether prolonged administration of low-dose peginterferon-α2a is associated with an increase in the rate and severity of depression compared to untreated controls.


METHODS
129 non-responders to full-dose peginterferon and ribavirin treatment were randomized to low-dose maintenance treatment with peginterferon-α2a 90 μg/week or no treatment for 3.5 years. Depression was assessed using the Beck Depression Inventory (BDI-II) and the Composite International Diagnostic Interview (CIDI) at baseline and at 12, 24, 36, and 48 months. "Clinical depression" was defined as BDI-II ≥11 and/or meeting DSM-IV criteria for major depression on the CIDI. Serial cortisol and serotonin plasma concentrations were obtained in a subgroup of patients.


RESULTS
Rates of clinical depression did not significantly differ over time or between treatment groups. Baseline clinical depression was the only significant predictor of clinical depression over time (p<0.001). Rates of clinical depression were also significantly higher in patients experiencing liver disease progression (p=0.016). Antidepressant use did not significantly differ between groups. Adjusted whole blood serotonin levels dropped significantly over time (p=0.04), but there was no group by time effect.


CONCLUSIONS
Lack of significant group differences in antidepressant use does not completely preclude significant mood changes masked by antidepressants. Results may differ in treatment naïve CHC patients or in those receiving full-dose peginterferon.


CONCLUSIONS
Prolonged low-dose peginterferon-α2a treatment is not associated with an increase in the frequency or severity of clinical depression in prior non-responder patients with chronic hepatitis C.
Kronfol
Ziad
Z
Depression Center, Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
Litman
Heather J
HJ
Back-Madruga
Carla
C
Bieliauskas
Linas A
LA
Lindsay
Karen L
KL
Lok
Anna S
AS
Fontana
Robert J
RJ
D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003866:Depressive Disorder / Q000139:chemically induced*; D018450:Disease Progression; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D011994:Recombinant Proteins; D012701:Serotonin / Q000097:blood; D013997:Time Factors
D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012701:Serotonin; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a; D006854:Hydrocortisone