QTc interval and its variability in patients with schizophrenia and healthy subjects: implications for a thorough QT study

Int J Neuropsychopharmacol. 2012 Nov;15(10):1535-40. doi: 10.1017/S1461145712000077. Epub 2012 Feb 8.


We compared heart rate-corrected QT interval (QTc) and its within- and between-subject variability, in ECGs recorded several days apart for 207 patients with schizophrenia (age range 19-60 yr) with age- and gender-matched healthy controls. Patients had higher heart rates (mean±s.d.) than controls [75±15 beats per minute (bpm) vs. 63±10 bpm; p<0.0001]. QTc by Bazett's formula (QTcB) overestimated QTc interval at high heart rates; consequently QTcB was longer in patients (412±24 ms) than in controls (404±24 ms; p=0.0003). QTc by Fridericia's method (QTcF), which was not influenced by heart rate, was comparable (398±22 ms in patients vs. 401±19 ms in controls; p=0.17). Between-subject variability in QTcF was similar in patients (17 ms) and controls (16.2 ms) but within-subject variability was larger (13.1 ms vs. 10 ms, respectively). Thus, a larger sample size is required when thorough QTc studies with a cross-over design are performed in patients with schizophrenia than in healthy subjects; sample size is not increased for studies with a parallel design. Last, QTcF is preferred over QTcB in schizophrenia patients with higher heart rates.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Case-Control Studies
  • Electrocardiography / methods*
  • Female
  • Heart Rate / physiology*
  • Humans
  • Male
  • Middle Aged
  • Schizophrenia / epidemiology
  • Schizophrenia / physiopathology*
  • Young Adult