Escitalopram for the prevention of peginterferon-α2a-associated depression in hepatitis C virus-infected patients without previous psychiatric disease: a randomized trial.
BACKGROUND
Depression is a major complication during treatment of chronic hepatitis C virus (HCV) infection with interferon-α (IFN-α). It is unclear whether antidepressants can prevent IFN-induced depression in patients without psychiatric risk factors.


OBJECTIVE
To examine whether preemptive antidepressant treatment with escitalopram can decrease the incidence or severity of depression associated with pegylated IFN-α in HCV-infected patients without a history of psychiatric disorders.


METHODS
Randomized, multicenter, double-blind, prospective, placebo-controlled, parallel-group trial. (ClinicalTrials.gov registration number: NCT00136318)


METHODS
10 university and 11 academic hospitals in Germany.


METHODS
181 HCV-infected patients with no history of psychiatric disorders enrolled between August 2004 and December 2008.


METHODS
Escitalopram, 10 mg/d (n = 90), or placebo (n = 91) administered 2 weeks before and for 24 to 48 weeks during antiviral therapy.


METHODS
The primary end point was the incidence of depression, defined as a Montgomery-Asberg Depression Rating Scale (MADRS) score of 13 or higher. Secondary end points were time to depression, incidence of major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, quality of life, sustained virologic response, tolerability, and safety.


RESULTS
32% (95% CI, 21% to 43%) of the patients in the escitalopram group developed a MADRS score of 13 or higher compared with 59% (CI, 48% to 69%) in the placebo group (absolute difference, 27 percentage points [CI, 12 to 42 percentage points]; P < 0.001). Major depression was diagnosed in 8% of the patients in the escitalopram group and 19% in the placebo group (absolute risk difference, 11 percentage points [CI, 5 to 15 percentage points]; P = 0.031). Tolerability and safety parameters did not differ between the groups. In the escitalopram group, 56% (CI, 46% to 66%) of patients achieved a sustained virologic response compared with 46% (CI, 37% to 57%) in the placebo group (P = 0.21).


CONCLUSIONS
Results might not be generalizable to patients with previous psychiatric disease. Some patients withdrew or developed temporary elevated MADRS scores after randomization but before the study medication was started.


CONCLUSIONS
Prophylactic antidepressant treatment with escitalopram was effective in reducing the incidence and severity of IFN-associated depression in HCV-infected patients without previous psychiatric disease.


BACKGROUND
Roche Pharma and Lundbeck.
Department of Psychiatry, Psychotherapy and Addiction Medicine, Kliniken Essen-Mitte, Henricistr. 92, 45136 Essen, Germany. m.schaefer@kliniken-essen-mitte.de
Martin
M
Schaefer
Rahul
R
Sarkar
Viola
V
Knop
Susanne
S
Effenberger
Astrid
A
Friebe
Loni
L
Heinze
Ulrich
U
Spengler
Thomas
T
Schlaepfer
Jens
J
Reimer
Peter
P
Buggisch
Johann
J
Ockenga
Ralph
R
Link
Michael
M
Rentrop
Hans
H
Weidenbach
Gwendolyn
G
Fromm
Klaus
K
Lieb
Thomas F
TF
Baumert
Andreas
A
Heinz
Thomas
T
Discher
Konrad
K
Neumann
Stefan
S
Zeuzem
Thomas
T
Berg
D000328:Adult; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects*; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use*; D003863:Depression / Q000139:chemically induced / Q000517:prevention & control*; D003865:Major Depressive Disorder / Q000139:chemically induced / Q000517:prevention & control; D004311:Double-Blind Method; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D012307:Risk Factors
D018687:Antidepressive Agents, Second-Generation; D000998:Antiviral Agents; D016898:Interferon-alpha; D015283:Citalopram