title: Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis.
abstract: OBJECTIVE
  To carry out a systematic review of the risk factors for, and incidence of, major depressive episode (MDE) related to antiviral therapy for chronic hepatitis C.
  
  
  METHODS
  The MEDLINE, PsycINFO, and Cochrane databases were searched to locate articles published from the earliest available online year until June 2011 using the keywords hepatitis C, interferon-alpha, peginterferon, pegylated interferon, depression, and mood and Boolean operators. Articles written in English, Spanish, and French were included.
  
  
  METHODS
  Prospective studies reporting incidence of interferon-alpha-induced MDE were included. At baseline, patients did not present a DSM-IV/ICD depressive episode, and evaluation was performed by a trained clinician. Twenty-six observational studies met the inclusion criteria.
  
  
  METHODS
  Extracted data included authors, year of publication, design, characteristics of the population, viral coinfection, adjunctive psychopharmacology, instruments to assess depression, dose and type of interferon-alpha, adjunctive ribavirin treatment, and follow-up time. Outcome of incidence of MDE (primary outcome measure) was abstracted, as were potential predictive variables.
  
  
  RESULTS
  A full review was performed. Meta-analysis of the cumulative incidence of induced MDE as a function of time was carried out. Odds ratios (ORs) and mean differences were used to estimate the strength of association of variables.
  
  
  RESULTS
  Overall cumulative incidence of depression was 0.25 (95% CI, 0.16 to 0.35) and 0.28 (95% CI, 0.17 to 0.42) at 24 and 48 weeks of treatment, respectively. According to our analysis, high baseline levels of interleukin 6 (mean difference = 1.81; 95% CI, 1.09 to 2.52), female gender (OR = 1.40; 95% CI, 1.02 to 1.91), history of MDE (OR = 3.96; 95% CI, 2.52 to 6.21), history of psychiatric disorder (OR = 3.18; 95% CI, 1.60 to 6.32), subthreshold depressive symptoms (mean difference = 0.96; 95% CI, 0.31 to 1.61), and low educational level (mean difference = -0.99; 95% CI, -1.59 to -0.39) were predictive variables of MDE during antiviral treatment.
  
  
  CONCLUSIONS
  One in 4 chronic hepatitis C patients who start interferon and ribavirin treatment will develop an induced major depressive episode. Clinicians should attempt a full evaluation of patients before starting antiviral treatment in order to identify those at risk of developing interferon-induced depression.
authors.affiliation: Clinical Institute of Neuroscience, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Udina
authors.forename: Pere
authors.initials: P
authors.lastname: Castellví
authors.forename: José
authors.initials: J
authors.lastname: Moreno-España
authors.forename: Ricard
authors.initials: R
authors.lastname: Navinés
authors.forename: Manuel
authors.initials: M
authors.lastname: Valdés
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
authors.forename: Klaus
authors.initials: K
authors.lastname: Langohr
authors.forename: Ricard
authors.initials: R
authors.lastname: Solà
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.forename: Rocío
authors.initials: R
authors.lastname: Martín-Santos
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology / Q000523:psychology; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a