title: CTN-194 (PICCO): design of a trial of citalopram for the prevention of depression and its consequences in HIV-hepatitis C co-infected individuals initiating pegylated interferon/ribavirin therapy.
abstract: Hepatitis C (HCV)-related end stage liver disease is a primary cause of morbidity and mortality in people with HIV. Despite this, co-infected patients have low rates of HCV treatment initiation and completion. This is in large part due to the risk of pegylated-interferon alpha (PEG-IFN-alpha)-related neuropsychiatric complications. We describe the design of a multicentre randomized, placebo-controlled trial that evaluates whether antidepressant prophylaxis is superior to early detection and treatment of depression in increasing the successful completion of HCV therapy. Seventy-six HIV+ adults with chronic HCV infection requiring therapy and with no contraindications to PEG-IFN-alpha/ribavirin will be randomized in a 1:1 ratio to receive citalopram or placebo starting three weeks prior to HCV treatment. A novel aspect of the trial design is the built-in management of emergent depression while maintaining the blinded treatment assignment. This will permit the comparison of prophylactic versus therapeutic use of citalopram. The primary outcome is the average proportion of prescribed PEG-IFN-alpha and ribavirin doses taken per month at weeks 12 and 24, and will be compared between treatment arms. The study will also compare the development of moderate-to-severe depression between treatment arms. A unique feature of this trial will be the use of Telepsychiatry to standardize observer-administered neuropsychiatric evaluations. Assessments of anxiety, quality of life, and adherence to therapy, as well as pathogenetic studies of neuropsychiatric side effects, will be conducted. Intention-to-treat analyses using random regression modeling will be employed to analyze longitudinal data on prescribed PEG-IFN-alpha and ribavirin doses. Survival analyses will be used to compare the time to the development of depression between the two arms. Effective prevention of a broad range of neuropsychiatric symptoms by citalopram has the potential to diminish PEG-IFN-alpha associated morbidity and consequently, allow a greater number of patients to complete full therapy.
authors.affiliation: Department of Medicine, Divisions of Infectious Diseases/Immunodeficiency, Royal Victoria Hospital, McGill University Health Centre, Montréal, Québec, Canada. marina.klein@muhc.mcgill.ca
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Brouillette
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Sheehan
authors.forename: Chawki
authors.initials: C
authors.lastname: Benkelfat
authors.forename: Lawrence
authors.initials: L
authors.lastname: Annable
authors.forename: Francine
authors.initials: F
authors.lastname: Weston
authors.forename: Deborah
authors.initials: D
authors.lastname: Kraus
authors.forename: Joel
authors.initials: J
authors.lastname: Singer
mesh_terms: D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D002170:Canada; D015283:Citalopram / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000523:psychology*; D006526:Hepatitis C / Q000188:drug therapy / Q000523:psychology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D011594:Psychometrics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D018401:Sample Size; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015283:Citalopram; D012254:Ribavirin