title: Citalopram for the prevention of depression and its consequences in HIV-hepatitis C coinfected individuals initiating pegylated interferon/ribavirin therapy: a multicenter randomized double-blind placebo-controlled trial.
abstract: BACKGROUND
  Depression related to interferon-alpha (IFN-α) is common, may reduce adherence, and can be treatment limiting. HIV-HCV coinfected persons experience lower sustained virologic response rates and commonly have psychiatric comorbidities, thus they may benefit from prevention of depression.
  
  
  OBJECTIVE
  The aim of the study was to determine whether prophylactic citalopram can increase HCV treatment adherence and reduce the incidence of moderate depression in HIV-HCV coinfected patients initiating PEG-IFN-α/ribavirin therapy.
  
  
  METHODS
  This was an investigator-initiated Canadian multicenter randomized, double-blind placebo-controlled trial. HIV-HCV coinfected patients were randomized in a 1:1 ratio to receive citalopram or placebo 3 weeks prior to starting PEG-IFN-α2b/ribavirin, stratified by study center and HCV genotype. The protocol design permitted the comparison of prophylaxis with the treatment of emergent depression. The primary outcomes were adherence (assessed through questionnaire and returned medication) and time to moderate depression measured by Beck Depression Inventory-II (BDI- II) score greater than 15, confirmed 2 weeks apart.
  
  
  RESULTS
  Seventy-six patients (36 citalopram/40 placebo) were randomized. Overall adherence was high, ranging from 95% (week 12) to 91% (week 48). There was no difference between arms with respect to mean or median adherence at any study time point. Cumulative incidence of moderate depression did not differ significantly by group (log rank P = .32). The hazard ratio for moderate depression was 0.81 (95% CI, 0.26 to 2.54) for citalopram compared with placebo when adjusted for baseline BDI-II score.
  
  
  CONCLUSIONS
  A strategy of prophylactic citalopram compared to treatment of emergent depression was not associated with higher adherence or a reduction in treatment-limiting depression nor did it significantly reduce depressive symptoms among HIV-HCV coinfected persons during treatment for HCV.
authors.affiliation: Division of Infectious Diseases/Chronic Viral Illness Service, Department of Medicine, Royal Victoria Hospital, McGill University Health Centre, Montréal, Québec, Canada Canadian HIV Trials Network, Vancouver, British Columbia, Canada.
authors.forename: Marina B
authors.initials: MB
authors.lastname: Klein
authors.affiliation: Canadian HIV Trials Network, Vancouver, British Columbia, Canada.
authors.forename: Terry
authors.initials: T
authors.lastname: Lee
authors.affiliation: Division of Infectious Diseases/Chronic Viral Illness Service, Department of Medicine, Royal Victoria Hospital, McGill University Health Centre, Montréal, Québec, Canada Department of Psychiatry, McGill University, Montréal, Québec, Canada Royal Victoria Hospital, McGill University Health Centre, Montréal, Québec, Canada.
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Brouillette
authors.affiliation: Division of Infectious Diseases/Chronic Viral Illness Service, Department of Medicine, Royal Victoria Hospital, McGill University Health Centre, Montréal, Québec, Canada Department of Pharmacy, McGill University Health Centre, Montréal, Québec, Canada Faculté de Pharmacie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Sheehan
authors.affiliation: Canadian HIV Trials Network, Vancouver, British Columbia, Canada University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sharon
authors.initials: S
authors.lastname: Walmsley
authors.affiliation: University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David K
authors.initials: DK
authors.lastname: Wong
authors.affiliation: Vancouver Infectious Diseases Research and Care Centre, Vancouver, British Columbia, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Conway
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Hull
authors.affiliation: Canadian HIV Trials Network, Vancouver, British Columbia, Canada The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Curtis
authors.initials: C
authors.lastname: Cooper
authors.affiliation: McMaster Health Science Centre, Hamilton, Ontario, Canada.
authors.forename: Shariq
authors.initials: S
authors.lastname: Haidar
authors.affiliation: Clinique médicale l'Actuel (VIH ITS Hépatites), Montréal, Québec, Canada Centre hospitalier de l'université de Montréal, Montréal, Québec, Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Vezina
authors.affiliation: Department of Psychiatry, McGill University, Montréal, Québec, Canada.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Annable
authors.affiliation: Department of Psychiatry, McGill University, Montréal, Québec, Canada Royal Victoria Hospital, McGill University Health Centre, Montréal, Québec, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Young
authors.affiliation: Canadian HIV Trials Network, Vancouver, British Columbia, Canada.
authors.forename: Wendy
authors.initials: W
authors.lastname: Zubyk
authors.affiliation: Canadian HIV Trials Network, Vancouver, British Columbia, Canada.
authors.forename: Joel
authors.initials: J
authors.lastname: Singer
mesh_terms: D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use*; D060085:Coinfection; D003863:Depression / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015283:Citalopram; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b
keywords: HIV; citalopram; coinfection; depression; hepatitis C virus; interferon-alpha