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

Sponsor:	Germans Trias i Pujol Hospital
Collaborators:	Hoffmann-La Roche H. Lundbeck A/S
Information provided by:	Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:	NCT00166296

Purpose

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	Intervention	Phase
Major Depressive Disorder. Hepatitis C, Chronic	Drug: Escitalopram Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: Depression Hepatitis Hepatitis C

Drug Information available for: Benzetimide Dexetimide Citalopram hydrobromide Citalopram Escitalopram Peginterferon Alfa-2a Escitalopram oxalate Interferons

U.S. FDA Resources

Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:

Major depressive episode following DSM-IV criteria. [ Time Frame: First three months of interferon treatment. ] [ Designated as safety issue: No ]
Viral response (HCV). [ Time Frame: At end of interferon treatment and after six months ] [ Designated as safety issue: Yes ]
Adverse side effects at any point during treatment. [ Time Frame: First 3 months of interferon therapy. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Total score in the Montgomery-Asberg Depression Rating Scale at baseline, and 4, 8 and 12 weeks after interferon treatment onset. [ Time Frame: First 3 months of interferon therapy. ] [ Designated as safety issue: No ]
Number of patients withdrawn from interferon due to depressive episode. [ Time Frame: First 3 months of interferon therapy. ] [ Designated as safety issue: No ]
Anxiety and Depression scores of the Hospital Anxiety and Depression Scale at baseline and after 4, 8 and 12 weeks of interferon treatment onset. [ Time Frame: First 3 months of interferon therapy. ] [ Designated as safety issue: No ]

Enrollment:	133
Study Start Date:	March 2005
Study Completion Date:	October 2007
Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Escitalopram, 15 mg/day	Drug: Escitalopram 15 mg/day starting 2 weeks before and 12 weeks during interferon therapy
B: Placebo Comparator Placebo	Drug: Placebo Placebo, 15 mg/day, starting 2 weeks before and for 12 weeks during interferon therapy.

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 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

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 IMAOs).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00166296

Locations

Spain
Hospital Universitari Germans Trias i Pujol
Badalona, Spain, 08916
Hospital Universitario de Salamanca
Salamanca, Spain
Fundacion Hospital Alcorcon
Alcorcon, Spain
Hospital Puerta de Hierro
Madrid, Spain
Hospital Universitario La Paz
Madrid, Spain
Hospital Universitario La Princesa
Madrid, Spain
Hospital Ramon y Cajal
Madrid, Spain
Hospital Nuestra Señora de Sonsoles
Avila, Spain
Hospital Consorci Sanitari de Terrassa
Tarrasa, Spain
Hospital Miguel Servet
Zaragoza, Spain
Hospital Parc Tauli
Sabadell, Spain
Hospital General Universitario
Valencia, Spain
Hospital Clínico Universitario
Valencia, Spain
Hospital La Fe
Valencia, Spain
Hospital del Mar
Barcelona, Spain

Sponsors and Collaborators

Germans Trias i Pujol Hospital

Hoffmann-La Roche

H. Lundbeck A/S

Investigators

Principal Investigator:	Crisanto Diez-Quevedo, MD	Germans Trias i Pujol University Hospital
Principal Investigator:	Ramon Planas, MD	Germans Trias i Pujol University Hospital

More Information

Publications:

Raison CL, Borisov AS, Broadwell SD, Capuron L, Woolwine BJ, Jacobson IM, Nemeroff CB, Miller AH. Depression during pegylated interferon-alpha plus ribavirin therapy: prevalence and prediction. J Clin Psychiatry. 2005 Jan;66(1):41-8.

Hauser P, Khosla J, Aurora H, Laurin J, Kling MA, Hill J, Gulati M, Thornton AJ, Schultz RL, Valentine AD, Meyers CA, Howell CD. A prospective study of the incidence and open-label treatment of interferon-induced major depressive disorder in patients with hepatitis C. Mol Psychiatry. 2002;7(9):942-7.

Hauser P, Soler R, Reed S, Kane R, Gulati M, Khosla J, Kling MA, Valentine AD, Meyers CA. Prophylactic treatment of depression induced by interferon-alpha. Psychosomatics. 2000 Sep-Oct;41(5):439-41. No abstract available.

Bonaccorso S, Marino V, Puzella A, Pasquini M, Biondi M, Artini M, Almerighi C, Verkerk R, Meltzer H, Maes M. Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system. J Clin Psychopharmacol. 2002 Feb;22(1):86-90.

Gleason OC, Yates WR, Isbell MD, Philipsen MA. An open-label trial of citalopram for major depression in patients with hepatitis C. J Clin Psychiatry. 2002 Mar;63(3):194-8.

Musselman DL, Lawson DH, Gumnick JF, Manatunga AK, Penna S, Goodkin RS, Greiner K, Nemeroff CB, Miller AH. Paroxetine for the prevention of depression induced by high-dose interferon alfa. N Engl J Med. 2001 Mar 29;344(13):961-6.

Ho SB, Nguyen H, Tetrick LL, Opitz GA, Basara ML, Dieperink E. Influence of psychiatric diagnoses on interferon-alpha treatment for chronic hepatitis C in a veteran population. Am J Gastroenterol. 2001 Jan;96(1):157-64.

Rowan PJ, Tabasi S, Abdul-Latif M, Kunik ME, El-Serag HB. Psychosocial factors are the most common contraindications for antiviral therapy at initial evaluation in veterans with chronic hepatitis C. J Clin Gastroenterol. 2004 Jul;38(6):530-4.

Loftis JM, Socherman RE, Howell CD, Whitehead AJ, Hill JA, Dominitz JA, Hauser P. Association of interferon-alpha-induced depression and improved treatment response in patients with hepatitis C. Neurosci Lett. 2004 Jul 22;365(2):87-91.

Schaefer M, Schwaiger M, Garkisch AS, Pich M, Hinzpeter A, Uebelhack R, Heinz A, van Boemmel F, Berg T. Prevention of interferon-alpha associated depression in psychiatric risk patients with chronic hepatitis C. J Hepatol. 2005 Jun;42(6):793-8. Epub 2005 Apr 2.

Schaefer M, Schmidt F, Folwaczny C, Lorenz R, Martin G, Schindlbeck N, Heldwein W, Soyka M, Grunze H, Koenig A, Loeschke K. Adherence and mental side effects during hepatitis C treatment with interferon alfa and ribavirin in psychiatric risk groups. Hepatology. 2003 Feb;37(2):443-51.

Responsible Party:	Germans Trias i Pujol Hospital ( Crisanto Diez-Quevedo )
Study ID Numbers:	PSQHEPGTP1, EudraCT number: 2004-002982-19
Study First Received:	September 9, 2005
Last Updated:	March 25, 2008
ClinicalTrials.gov Identifier:	NCT00166296 History of Changes
Health Authority:	Spain: Spanish Agency of Medicines

Keywords provided by Germans Trias i Pujol Hospital:

Major depressive disorder, chemically induced.
Peginterferon alfa-2a.
Escitalopram.
Chronic hepatitis C, psychology.
Prophylactic treatment.

Additional relevant MeSH terms:

Anti-Infective Agents
Parasympatholytics
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Liver Diseases
Molecular Mechanisms of Pharmacological Action
Cholinergic Antagonists
Hepatitis, Chronic
Flaviviridae Infections
Antineoplastic Agents
Anti-Dyskinesia Agents
Physiological Effects of Drugs
Psychotropic Drugs
Hepatitis, Viral, Human
Antiparkinson Agents

Depressive Disorder, Major
Cholinergic Agents
Mental Disorders
Therapeutic Uses
Hepatitis C
Antidepressive Agents, Second-Generation
Dexetimide
Antidepressive Agents
RNA Virus Infections
Depression
Interferons
Depressive Disorder
Antiviral Agents
Serotonin Uptake Inhibitors
Citalopram

ClinicalTrials.gov processed this record on February 08, 2010