title: Influence of different second generation antipsychotics on the QTc interval: A pragmatic study.
abstract: OBJECTIVE
  To investigate whether differential influence on the QTc interval exists among four second generation antipsychotics (SGAs) in psychosis.
  
  
  METHODS
  Data were drawn from a pragmatic, randomized head-to-head trial of the SGAs risperidone, olanzapine, quetiapine, and ziprasidone in acute admissions patients with psychosis, and with follow-up visits at discharge or maximally 6-9 wk, 3, 6, 12 and 24 mo. Electrocardiograms were recorded on all visits. To mimic clinical shared decision-making, the patients were randomized not to a single drug, but to a sequence of the SGAs under investigation. The first drug in the sequence defined the randomization group, but the patient and/or clinician could choose an SGA later in the sequence if prior negative experiences with the first one(s) in the sequence had occurred. The study focuses on the time of, and actual use of the SGAs under investigation, that is until treatment discontinuation or change, in order to capture the direct medication effects on the QTc interval. Secondary intention-to-treat (ITT) analyses were also performed.
  
  
  RESULTS
  A total of 173 patients, with even distribution among the treatment groups, underwent ECG assessments. About 70% were males and 43% had never used antipsychotic drugs before the study. The mean antipsychotic doses in milligrams per day with standard deviations (SD) were 3.4 (1.2) for risperidone, 13.9 (4.6) for olanzapine, 325.9 (185.8) for quetiapine, and 97.2 (42.8) for ziprasidone treated groups. The time until discontinuation of the antipsychotic drug used did not differ in a statistically significant way among the groups (Log-Rank test:P= 0.171). The maximum QTc interval recorded during follow-up was 462 ms. Based on linear mixed effects analyses, the QTc interval change per day with standard error was -0.0030 (0.0280) for risperidone; -0.0099 (0.0108) for olanzapine; -0.0027 (0.0170) for quetiapine, and -0.0081 (0.0229) for ziprasidone. There were no statistically significant differences among the groups in this regard. LME analyses based on ITT groups (the randomization groups), revealed almost identical slopes with -0.0063 (0.0160) for risperidone, -0.0130 (0.0126) for olanzapine, -0.0034 (0.0168) for quetiapine, and -0.0045 (0.0225) for ziprasidone.
  
  
  CONCLUSIONS
  None of the SGAs under investigation led to statistically significant QTc prolongation. No statistically significant differences among the SGAs were found.
authors.affiliation: Roy E Olsen, Rune A Kroken, Sigmund Bjørhovde, Kristina Aanesen, Erik Johnsen, Division of Psychiatry, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Roy E
authors.initials: RE
authors.lastname: Olsen
authors.affiliation: Roy E Olsen, Rune A Kroken, Sigmund Bjørhovde, Kristina Aanesen, Erik Johnsen, Division of Psychiatry, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Rune A
authors.initials: RA
authors.lastname: Kroken
authors.affiliation: Roy E Olsen, Rune A Kroken, Sigmund Bjørhovde, Kristina Aanesen, Erik Johnsen, Division of Psychiatry, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Sigmund
authors.initials: S
authors.lastname: Bjørhovde
authors.affiliation: Roy E Olsen, Rune A Kroken, Sigmund Bjørhovde, Kristina Aanesen, Erik Johnsen, Division of Psychiatry, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Kristina
authors.initials: K
authors.lastname: Aanesen
authors.affiliation: Roy E Olsen, Rune A Kroken, Sigmund Bjørhovde, Kristina Aanesen, Erik Johnsen, Division of Psychiatry, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Jørgensen
authors.affiliation: Roy E Olsen, Rune A Kroken, Sigmund Bjørhovde, Kristina Aanesen, Erik Johnsen, Division of Psychiatry, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Else-Marie
authors.initials: EM
authors.lastname: Løberg
authors.affiliation: Roy E Olsen, Rune A Kroken, Sigmund Bjørhovde, Kristina Aanesen, Erik Johnsen, Division of Psychiatry, Haukeland University Hospital, 5021 Bergen, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Johnsen
keywords: Antipsychotics; Clinical trial; Pragmatic design; Psychosis; QTc prolongation