Clinical trial NCT00166296: Efficacy and Safety of Escitalopram for Prevention of Depression Induced by Peg-Interferon in Hepatitis C Patients
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Hepatitis C, Chronic
Keywords: Major depressive disorder, chemically induced.
Peginterferon alfa-2a.
Escitalopram.
Chronic hepatitis C, psychology.
Prophylactic treatment.
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
name: H. Lundbeck A/S
First posted: 2005-09-14
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility 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-).

Primary outcomes:
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.
timeFrame: First three months of interferon treatment.
measure: Number of Participants With Sustained Hepatitis C Viral Response (Negativization of Serum Hepatitis C Virus Ribonucleic Acid).
timeFrame: Six months after the end of interferon treatment
Secondary outcomes:
measure: Total Score in the Montgomery-Asberg Depression Rating Scale
timeFrame: 12 weeks after interferon treatment onset
measure: Total Score in the Depression Subscale of the Hospital Anxiety and Depression Scale.
timeFrame: 12 weeks after interferon treatment onset
Other outcomes:
Locations:
city: Alcorcon
country: Spain
facility: Fundacion Hospital Alcorcon
city: Avila
country: Spain
facility: Hospital Nuestra Señora de Sonsoles
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa
city: Sabadell
country: Spain
facility: Hospital Parc Tauli
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Tarrasa
country: Spain
facility: Hospital Consorci Sanitari de Terrassa
city: Valencia
country: Spain
facility: Hospital Clínico Universitario
city: Valencia
country: Spain
facility: Hospital General Universitario
city: Valencia
country: Spain
facility: Hospital La Fe
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
Study officials:
affiliation: Germans Trias i Pujol University Hospital
name: Crisanto Diez-Quevedo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Germans Trias i Pujol University Hospital
name: Ramon Planas, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Diez-Quevedo C, Masnou H, Planas R, Castellvi P, Gimenez D, Morillas RM, Martin-Santos R, Navines R, Sola R, Giner P, Ardevol 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.