Prophylaxis of Psychiatric Symptoms During Anti-HCV Treatment

Condition(s) targeted: Hepatitis C

Intervention: Escitalopram (Drug); Placebo (Other)

Phase: Phase 2/Phase 3

Status: Active, not recruiting

Sponsored by: Foundation for Liver Research

Official(s) and/or principal investigator(s):
Robert J De Knegt, MD, Principal Investigator, Affiliation: Erasmus MC University Hospital

The treatment of chronic hepatitis C with peginterferon and ribavirin is highly effective but is hampered by peginterferon-induced psychopathology.

Prevention of peginterferon-induced psychopathology with selective serotonin reuptake inhibitors (SSRI's) (paroxetine) has been shown to be effective in patients treated with interferon for malignant disease. The aim is to study the effects of prophylactic treatment with escitalopram (another SSRI) on peginterferon-associated psychopathology in patients treated with peginterferon and ribavirin for chronic hepatitis C.

Official title: Prophylactic Treatment of Peginterferon-Associated Psychopathology. A Double-Blind Placebo-Controlled Trial on the Effects of Escitalopram (Lexapro®) in Patients Treated With Peginterferon and Ribavirin (POPS Study)

Study design: Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Occurrence of peginterferon-induced psychiatric disturbance

Secondary outcome: Occurrence of major depression

Detailed description: The treatment of chronic hepatitis C with peginterferon and ribavirin is highly effective but is hampered by peginterferon-induced psychopathology.

Prevention of peginterferon-induced psychopathology with SSRI's (paroxetine) has been shown to be effective in patients treated with interferon for malignant disease. The aim is to study the effects of prophylactic treatment with escitalopram on peginterferon-associated psychopathology in patients treated with peginterferon and ribavirin for chronic hepatitis C.

Design: double blind, randomized controlled trial with two arms, maximum 40 patients per arm. Patients, starting with peginterferon and ribavirin, will be randomized to receive escitalopram therapy 10 mg per day (however, 5 mg in the first two weeks) or placebo.

Study population and selection: eighty patients receiving peginterferon alfa-2a (Pegasys 180 microgram) and ribavirin (Copegus 400 mg twice daily) will be included in the study.

Aims of the study:

1. to asses whether prophylactic treatment with escitalopram avoids significantly the occurrence of peginterferon-induced psychiatric disturbance; defined as an increase of two points on observer-based rating scales reflecting anxiety (BAS: BriefAnxietyScale), loss of concentration, depression and loss of impulse control (Montgomery and Asberg Depression Rating Scale: MADRS), and

2. to assess the frequency of major depression according to DSM IV criteria, in the escitalopram and placebo-treated patients.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male and female patients between 18-70 years of age

- Evidence of chronic hepatitis C by detectable serum HCV-DNA

- Hepatitis C genotype 1,2,3 or 4

- Indication for antiviral therapy of hepatitis C according to current clinical

guidelines

- Written informed consent

Exclusion Criteria:

- History or other evidence of severe illness, malignancy or any other condition which

would make the patient, in the opinion of the investigator, unsuitable for the study

- Abnormal thyroid stimulating hormone (TSH)

- Presence of contra-indications for antiviral therapy

- Concurrent psychiatric axis I diagnosis according to Diagnostic and Statistical Manual

of Mental Disorders, Fourth Edition (DSM IV) criteria, as the presence of a major depressive episode, bipolar disorder or psychotic disorder.

- Concurrent use of psychotropic drugs such as MAO-inhibitors, St John's wort, Lithium

and 5 HT-agonists and antiepileptics.

Radboud University Hospital, Nijmegen 6500 HB, Netherlands

AMC, Amsterdam 1100DD, Netherlands

Erasmus MC University Hospital, Rotterdam, Zuid-Holland 3015GD, Netherlands

Starting date: August 2005
Ending date: December 2008
Last updated: July 31, 2007