Official Title: “Study of the Efficacy and Safety of Escitalopram for the Prevention of Depressive Episodes Induced by Peg-Interferon Alpha2a and Ribavirin in Chronic Hepatitis C Patients. Randomized, Double-Blind, Placebo-Controlled Clinical Trial”

The purpose of this study is to determine whether the use of an antidepressant (escitalopram) can prevent depressive episodes that appear during the treatment with peg-interferon and ribavirin in patients with chronic hepatitis C.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2007

Chronic hepatitis C is a prevalent condition, and the main cause of chronic liver diseases, including cirrhosis and cancer. Nowadays, interferon-alfa in combination with ribavirin is the main treatment option for this condition. In the last years, interferon molecule has been modified in order to improve tolerance into pegylated interferon.

Interferon-alfa has been associated with a high prevalence of psychiatric side effects, especially major depression (up to 25% of the cases), which is one of the main concerns about using this treatment. In fact, major depression is one of the main reasons of treatment withdrawal and treatment failure.

Major depression induced by interferon-alfa can be successfully treated with antidepressants, but we don't know if antidepressants can also prevent the development of major depression, and if this can be a safe intervention. In the literature, there is only one controlled trial about this issue, in cancer patients, and some open studies in hepatitis C.

In order to evaluate the efficacy, and safety, of an antidepressant (escitalopram) for preventing peginterferon's induced depressive episodes in patients with chronic hepatitis C, we have designed this 14-weeks placebo-controlled, double-blind, randomized clinical trial.

Study interventions will be started two weeks before peginterferon + ribavirin's treatment onset.

Subjects included in the study will be patients with chronic hepatitis C who are going to be treated with peginterferon-alfa2a + ribavirin, and without mental disorders requiring active psychotropic treatment.

The main variables studied will be the appearance of a major depressive episode, following DSM-IV criteria, and the total score on the Montgomery-Asberg Depression Rating Scale, along three assessment points at 4, 8 and 12 weeks of treatment with interferon. There will also be a follow-up period of up to 6 months after treatment with interferon is completed.

Intervention(s) in this Clinical Trial

• Drug: Escitalopram
  • 15 mg/day starting 2 weeks before and 12 weeks during interferon therapy
• Drug: Placebo
  • Placebo, 15 mg/day, starting 2 weeks before and for 12 weeks during interferon therapy.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Escitalopram, 15 mg/day
• Placebo Comparator: B
  • Placebo

Primary Measures

• Major depressive episode following DSM-IV criteria.
  • Time Frame: First three months of interferon treatment.
    Safety Issue?: No
• Viral response (HCV).
  • Time Frame: At end of interferon treatment and after six months
    Safety Issue?: Yes
• Adverse side effects at any point during treatment.
  • Time Frame: First 3 months of interferon therapy.
    Safety Issue?: Yes

Secondary Measures

• Total score in the Montgomery-Asberg Depression Rating Scale at baseline, and 4, 8 and 12 weeks after interferon treatment onset.
  • Time Frame: First 3 months of interferon therapy.
    Safety Issue?: No
• Number of patients withdrawn from interferon due to depressive episode.
  • Time Frame: First 3 months of interferon therapy.
    Safety Issue?: No
• Anxiety and Depression scores of the Hospital Anxiety and Depression Scale at baseline and after 4, 8 and 12 weeks of interferon treatment onset.
  • Time Frame: First 3 months of interferon therapy.
    Safety Issue?: No

Inclusion Criteria:

• Patients with chronic hepatitis C who are going to initiate treatment with peginterferon alfa2a + ribavirin.
• Age 18-65 years.
• Signed informed consent.
• If female, they are not in fertile period or they use barrier contraceptives.
• Patients able to understand and fill written questionnaires.

Exclusion Criteria:

• Hepatic cirrhosis or carcinoma.
• Less than 4000/mm3 leucocytes, or less than 70000/mm3 platelets.
• Hemoglobin less than 11 g/dL (females) or 12 (males).
• Any risk factor for hemolysis.
• Comorbid severe medical conditions (kidney, immune system, lung, heart, thyroid, etc).
• Baseline mental disorders that require antidepressants (depressive disorders and anxiety disorders).
• Other baseline mental disorders (delirium, substance use disorders).
• Mental disorders at any time (dementia, psychotic disorders, bipolar disorders.
• Contraindications of escitalopram (hypersensibility, diabetes, patients using serotoninergic agents, drugs that enhance the risk of bleeding, or IMAOs).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Germans Trias i Pujol Hospital

Overall Clinical Trial Officials and Contacts

Crisanto Diez-Quevedo, MD Principal Investigator Germans Trias i Pujol University Hospital  

Information obtained from ClinicalTrials.gov on October 06, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00166296

Study ID Number: PSQHEPGTP1

ClinicalTrials.gov Identifier: NCT00166296

Health Authority: Spain: Spanish Agency of Medicines