title: First-generation antipsychotics and QTc: any role for mediating variables?
abstract: Corrected QT (QTc) interval prolongation is often associated with use of first-generation antipsychotics (FGAs). However, other factors require appropriate consideration, including age and gender, the role of other known medications associated with QTc prolongation, and severe comorbid conditions, such as co-occurring alcohol abuse/dependence. We aimed to study potential mediating roles of different, related, candidate variables on QTc.
  
  
  
  We capitalized on data from a large (N = 2366), cross-sectional, national survey, the STAR Network QTc study, using a representative sample of people taking FGAs, and recruited from mental health services across Italy.
  
  
  
  About one-third of the sample was treated with FGAs, and almost one-tenth of the subjects took a different, additional, drug known to cause QTc prolongation. Our findings confirmed that there is an impact from FGAs, age, gender, alcohol misuse, and concurrent risky drugs on QTc. However, comorbid alcohol abuse/dependence and concurrent risky drugs did not mediate the effect of FGAs on QTc.
  
  
  
  Our findings showed that FGAs, concurrent risky drugs, and alcohol use disorders prolonged QTc. FGAs had a direct effect on QTc, confirming the need for clinicians to monitor a risk that could lead to sudden unexplained death. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Division of Psychiatry, University College London, London, UK.|Department of Medicine and Surgery, University of Milano Bicocca, Monza (MB), Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carrà
authors.affiliation: Department of Medicine and Surgery, University of Milano Bicocca, Monza (MB), Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Crocamo
authors.affiliation: Department of Medicine and Surgery, University of Milano Bicocca, Monza (MB), Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bartoli
authors.affiliation: Department of Medicine and Surgery, University of Milano Bicocca, Monza (MB), Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Lax
authors.affiliation: Department of Medicine and Surgery, University of Milano Bicocca, Monza (MB), Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Tremolada
authors.affiliation: Department of Mental Health, Siena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Lucii
authors.affiliation: Department of Neuroscience, Imaging and Clinical Sciences, University of Chieti, Chieti, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinotti
authors.affiliation: WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Nosè
authors.affiliation: WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Bighelli
authors.affiliation: WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ostuzzi
authors.affiliation: WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy.
authors.forename: Mariasole
authors.initials: M
authors.lastname: Castellazzi
authors.affiliation: Department of Medicine and Surgery, University of Milano Bicocca, Monza (MB), Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Clerici
authors.affiliation: WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Barbui
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D008875:Middle Aged
chemical_list: D014150:Antipsychotic Agents
keywords: QT prolongation; alcohol; antipsychotic agents; drug therapy combination; risk factors