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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Major Depressive Disorder, Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Escitalopram
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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-).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Escitalopram<br>Escitalopram, 15 mg/day | Drug: Escitalopram<br>* 15 mg/day starting 2 weeks before and 12 weeks during interferon therapy<br>* Other names: Cipralex;|
| Placebo Comparator: Placebo pill<br>Placebo | Drug: Placebo<br>* Placebo, 15 mg/day, starting 2 weeks before and for 12 weeks during interferon therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | At least five of the symptoms have been present during the same 1-week period: depressed mood, loss of interest or pleasure, weight or appetite changes, insomnia, agitation or retardation, fatigue, feelings of worthlessness or guilt, diminished ability to think or concentrate, recurrent thoughts of death. At least one of the symptoms is either depressed mood or loss of interest. Diagnoses were made by a trained psychiatrist who applied the mood disorders module from the Structured Clinical Interview for DSM-IV Axis I Disorders, non-patient edition (SCID-I/NP) at each study evaluation. | First three months of interferon treatment. | 
| Number of Participants With Sustained Hepatitis C Viral Response (Negativization of Serum Hepatitis C Virus Ribonucleic Acid). | Number of participants with negativization of serum hepatitis C Virus Ribonucleic Acid (HCV RNA) 6 months after concluding antiviral therapy (sustained viral response). Negativization was defined as the absence of detectable levels of serum HCV RNA using a polymerase chain reaction. | Six months after the end of interferon treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Score in the Montgomery-Asberg Depression Rating Scale | The MADRS is a 10-item scale, clinician-administered, which is sensitive to symptom change during antidepressant treatment. It has been frequently used to measure depressive symptoms during interferon-alpha therapy and exhibits improved internal consistency in patients with co-morbid medical conditions compared with other clinician-administered questionnaires. Items are rated on a scale of 0-6. Scores range from 0 to 60, higher scores meaning higher levels of depression. | 12 weeks after interferon treatment onset | 
| Total Score in the Depression Subscale of the Hospital Anxiety and Depression Scale. | The Hospital Anxiety and Depression Scale (HADS) is 14-item scale, patient-administered, that allows two independent scores of depression and anxiety. It has been specially designed to apply in patients with comorbid medical conditions as it excludes somatic or vegetative symptoms from the depression subscale. We present data of de depression subscale. The seven-item Depression subscale yields a score of 0-21, with higher scores meaning higher levels of depressive symptoms. | 12 weeks after interferon treatment onset | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major depressive disorder, chemically induced., Peginterferon alfa-2a., Escitalopram., Chronic hepatitis C, psychology., Prophylactic treatment.