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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00166296
Recruitment Status : Completed
First Posted : September 14, 2005
Results First Posted : March 30, 2011
Last Update Posted : August 17, 2020
Hoffmann-La Roche
H. Lundbeck A/S
Information provided by:
Germans Trias i Pujol Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Hepatitis C, Chronic Drug: Escitalopram Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 133 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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 Start Date : March 2005
Actual Primary Completion Date : October 2007
Actual Study Completion Date : October 2007

Arm Intervention/treatment
Experimental: Escitalopram
Escitalopram, 15 mg/day
Drug: Escitalopram
15 mg/day starting 2 weeks before and 12 weeks during interferon therapy
Other Name: Cipralex

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

Primary Outcome Measures :
  1. 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. [ Time Frame: First three months of interferon 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.

  2. Number of Participants With Sustained Hepatitis C Viral Response (Negativization of Serum Hepatitis C Virus Ribonucleic Acid). [ Time Frame: Six months after the end of interferon treatment ]

    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.

Secondary Outcome Measures :
  1. Total Score in the Montgomery-Asberg Depression Rating Scale [ Time Frame: 12 weeks after interferon treatment onset ]

    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.

  2. Total Score in the Depression Subscale of the Hospital Anxiety and Depression Scale. [ Time Frame: 12 weeks after interferon treatment onset ]

    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   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 monoamineoxidase inhibitors -MAOIs-).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00166296

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Fundacion Hospital Alcorcon
Alcorcon, Spain
Hospital Nuestra Señora de Sonsoles
Avila, Spain
Hospital Universitari Germans Trias i Pujol
Badalona, Spain, 08916
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
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Hoffmann-La Roche
H. Lundbeck A/S
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Principal Investigator: Crisanto Diez-Quevedo, MD Germans Trias i Pujol University Hospital
Principal Investigator: Ramon Planas, MD Germans Trias i Pujol University Hospital
Publications of Results:
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Responsible Party: Crisanto Diez-Quevedo, Germans Trias i Pujol Hospital Identifier: NCT00166296    
Other Study ID Numbers: PSQHEPGTP1
EudraCT number: 2004-002982-19
First Posted: September 14, 2005    Key Record Dates
Results First Posted: March 30, 2011
Last Update Posted: August 17, 2020
Last Verified: August 2020
Keywords provided by Germans Trias i Pujol Hospital:
Major depressive disorder, chemically induced.
Peginterferon alfa-2a.
Chronic hepatitis C, psychology.
Prophylactic treatment.
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Depressive Disorder
Depressive Disorder, Major
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Mood Disorders
Mental Disorders
Behavioral Symptoms
Hepatitis, Chronic
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs