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

This study has been completed.
Sponsor:
Collaborators:
Hoffmann-La Roche
H. Lundbeck A/S
Information provided by:
Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT00166296
First received: September 9, 2005
Last updated: March 4, 2011
Last verified: March 2011

September 9, 2005
March 4, 2011
March 2005
October 2007   (final data collection date for primary outcome measure)
  • 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. ] [ Designated as safety issue: No ]

    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.

  • 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 ] [ Designated as safety issue: Yes ]

    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.

  • Major depressive episode following DSM-IV criteria during the first three months of interferon treatment.
  • Viral response (HCV) at end of interferon treatment and after six months.
  • Adverse side effects at any point during treatment.
Complete list of historical versions of study NCT00166296 on ClinicalTrials.gov Archive Site
  • Total Score in the Montgomery-Asberg Depression Rating Scale [ Time Frame: 12 weeks after interferon treatment onset ] [ Designated as safety issue: No ]

    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.

  • Total Score in the Depression Subscale of the Hospital Anxiety and Depression Scale. [ Time Frame: 12 weeks after interferon treatment onset ] [ Designated as safety issue: No ]

    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.

  • Total score in the Montgomery-Asberg Depression Rating Scale at baseline, and 4, 8 and 12 weeks after interferon treatment onset.
  • Number of patients withdrawn from interferon due to depressive episode.
  • Anxiety and Depression scores of the Hospital Anxiety and Depression Scale at baseline and after 4, 8 and 12 weeks of interferon treatment onset.
Not Provided
Not Provided
 
Efficacy and Safety of Escitalopram for Prevention of Depression Induced by Peg-Interferon in Hepatitis C Patients
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Major Depressive Disorder.
  • Hepatitis C, Chronic
  • Drug: Escitalopram
    15 mg/day starting 2 weeks before and 12 weeks during interferon therapy
    Other Name: Cipralex
  • Drug: Placebo
    Placebo, 15 mg/day, starting 2 weeks before and for 12 weeks during interferon therapy.
  • Experimental: Escitalopram
    Escitalopram, 15 mg/day
    Intervention: Drug: Escitalopram
  • Placebo Comparator: Placebo pill
    Placebo
    Intervention: Drug: Placebo
Diez-Quevedo C, Masnou H, Planas R, Castellví P, Giménez D, Morillas RM, Martín-Santos R, Navinés R, Solà R, Giner P, Ardèvol M, Costa J, Diago M, Pretel J. Prophylactic treatment with escitalopram of pegylated interferon alfa-2a-induced depression in hepatitis C: a 12-week, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011 Apr;72(4):522-8. doi: 10.4088/JCP.09m05282blu. Epub 2010 Oct 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
133
October 2007
October 2007   (final data collection date for primary outcome measure)

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-).
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT00166296
PSQHEPGTP1, EudraCT number: 2004-002982-19
No
Crisanto Diez-Quevedo, Germans Trias i Pujol Hospital
Germans Trias i Pujol Hospital
  • Hoffmann-La Roche
  • H. Lundbeck A/S
Principal Investigator: Crisanto Diez-Quevedo, MD Germans Trias i Pujol University Hospital
Principal Investigator: Ramon Planas, MD Germans Trias i Pujol University Hospital
Germans Trias i Pujol Hospital
March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP