Session Title: Category 5g. VIRAL HEPATITIS: g. HEPATITIS C - CLINICAL (THERAPY)
Presentation Date: Apr 15, 2010
ASSESSMENT OF PAROXETINE IN THE PREVENTION OF DEPRESSION IN PATIENTS WITH CHRONIC HEPATITIS C TREATED BY PEG-INTERFERON-RIBAVIRIN.: A DOUBLE-BLINDED, RANDOMIZED STUDY. ANRS HC18 PAROPEG
J.-P. Bronowicki1*, V. Canva2, A. Tran3, M.-N. Hilleret4, S. Pol5, M. Mainard6, M. Bourlière7, V. de Ledinghen8, A. Abergel9, K. Barange10, N. Ganne11, P. Cales12, V. Di Martino13, O. Goria14, J.-M. Molina15, L. Alric10, J.-J. Raabe16
1CHU de Nancy, Vandoeuvre-lès-Nancy, 2CHU de Lille, Lille, 3CHU de Nice, Nice, 4CHU de Grenoble, Grenoble, 5Hopital Cochin, Paris, 6CHU de Lyon, Lyon, 7Hopital Saint Joseph, Marseille, 8CHU de Bordeaux - Hopital Pellegrin, Bordeaux, 9CHU de Clermont Ferrand, Clermont Ferrand, 10CHU de Toulouse, Toulouse, 11Hopital Jean Verdier, Bondy, 12CHU Angers, Angers, 13CHU de Besançon, Besançon, 14CHU de Rouen, Rouen, 15Hopital Saint-Louis, Paris, 16CHR Metz, Metz, France. *firstname.lastname@example.org
Background/aim: Treatment with PEG-interferon (PEG-IFN) for chronic hepatitis C (CHC) is associated with depression. The aim of the study was to determine the efficacy of paroxetine for preventing depression induced by PEG-IFN in CHC patients.
Methods: We designed a prospective, multicenter, double-blind, placebo-controlled trial of the antidepressant paroxetine in CHC adult patients who were eligible for therapy with PEG-IFN-alpha 2a or 2b and ribavirin [NCT00196664]. Patients with symptomatic mental disorders at baseline were excluded, as well as those with HBV or HIV coinfection. The study was conducted in 17 French hospitals. Patients were randomly assigned to receive paroxetine (20 mg/day, n= 73) or placebo (n=76). Stratification was done on: PEG-IFN (2a vs 2b), history of previous antiviral treatment (no vs yes), HCV genotype (1/4/5 vs 2/3). Treatment was begun 2 weeks before PEG-IFN and continued until 2 weeks after the end of the antiviral therapy. Patients were evaluated every month until the end of PEG-IFN. Main variables were the presence of a major depression evaluated by the Mini International Neuropsychiatric Interview (MINI) and a Montgomery-Asberg Depression Rating Scale (MADRS)> 15. We hypothesized a 20 % decrease of depression incidence with paroxetine. Chi-square test and Student's T test were used for categorical and continuous variables respectively.
Results: The characteristics of the 159 included patients were as follow: male: 58 %, age: 50 years, history of psychiatric disorders: 30 %, history of drug use: 32 %, METAVIR F3-F4: 48 %, genotype 1/4/5: 58 %. 64 % patients were naïve of treatment and 52 % received PEG-IFN 2a. The 2 arms were well matched. The incidence of depression was not statistically different between the 2 arms according to the MINI (paroxetine: 4 % vs 11 %) and the MADRS (paroxetine: 18 vs 28 %). There was no difference in terms of antiviral dose reduction (34% vs 36 %) and serious adverse events (22% vs 14%). The SVR rates were also comparable (46 vs 54 %).
Conclusion: Our results do not support the systematic use of paroxetine in the prevention of the depression induced by PEG-IFN in the treatment of CHC.