Efficacy and Safety of Escitalopram for Prevention of Depression Induced by Peg-Interferon in Hepatitis C Patients

Condition(s) targeted: Major Depressive Disorder.; Hepatitis C, Chronic

Intervention: Escitalopram (Drug); Placebo (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Germans Trias i Pujol Hospital

Official(s) and/or principal investigator(s):
Crisanto Diez-Quevedo, MD, Principal Investigator, Affiliation: Germans Trias i Pujol University Hospital
Ramon Planas, MD, Principal Investigator, Affiliation: Germans Trias i Pujol University Hospital

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome:

Number of Participants Who Developed a Major Depressive Episode According to Diagnostic & Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) Criteria During the First 12 Weeks of Antiviral Treatment.

Number of Participants With Sustained Hepatitis C Viral Response (Negativization of Serum Hepatitis C Virus Ribonucleic Acid).

Secondary outcome:

Total Score in the Montgomery-Asberg Depression Rating Scale

Total Score in the Depression Subscale of the Hospital Anxiety and Depression Scale.

Detailed description: 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 Diagnostic & Statistical Manual of Mental Disorders (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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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 monoamineoxidase

inhibitors - MAOIs-).

Fundacion Hospital Alcorcon, Alcorcon, Spain

Hospital Nuestra Señora de Sonsoles, Avila, Spain

Hospital Universitari Germans Trias i Pujol, Badalona 08916, Spain

Hospital del Mar, Barcelona, Spain

Hospital Puerta de Hierro, Madrid, Spain

Hospital Ramon y Cajal, Madrid, Spain

Hospital Universitario La Paz, Madrid, Spain

Hospital Universitario La Princesa, Madrid, Spain

Hospital Parc Tauli, Sabadell, Spain

Hospital Universitario de Salamanca, Salamanca, Spain

Hospital Consorci Sanitari de Terrassa, Tarrasa, Spain

Hospital Clínico Universitario, Valencia, Spain

Hospital General Universitario, Valencia, Spain

Hospital La Fe, Valencia, Spain

Hospital Miguel Servet, Zaragoza, Spain

Starting date: March 2005
Last updated: March 4, 2011