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Influence of Olanzapine on QT Variability and Complexity Measures of Heart Rate in Patients With Schizophrenia

Bär, Karl-Jürgen MD*; Koschke, Mandy*; Berger, Sandy MD*; Schulz, Steffen MD; Tancer, Manuel MD; Voss, Andreas PhD; Yeragani, Vikram K. MD§

Journal of Clinical Psychopharmacology: December 2008 - Volume 28 - Issue 6 - p 694-698
doi: 10.1097/JCP.0b013e31818a6d25
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Previous studies have shown that untreated patients with acute schizophrenia present with reduced heart rate variability and complexity as well as increased QT variability. This autonomic dysregulation might contribute to increased cardiac morbidity and mortality in these patients. However, the additional effects of newer antipsychotics on autonomic dysfunction have not been investigated, applying these new cardiac parameters to gain information about the regulation at sinus node level as well as the susceptibility to arrhythmias.

We have investigated 15 patients with acute schizophrenia before and after established olanzapine treatment and compared them with matched controls. New nonlinear parameters (approximate entropy, compression entropy, fractal dimension) of heart rate variability and also the QT-variability index were calculated.

In accordance with previous results, we have observed reduced complexity of heart rate regulation in untreated patients. Furthermore, the QT-variability index was significantly increased in unmedicated patients, indicating increased repolarization lability. Reduction of the heart rate regulation complexity after olanzapine treatment was seen, as measured by compression entropy of heart rate. No change in QT variability was observed after treatment.

This study shows that unmedicated patients with acute schizophrenia experience autonomic dysfunction. Olanzapine treatment seems to have very little additional impact in regard to the QT variability. However, the decrease in heart rate complexity after olanzapine treatment suggests decreased cardiac vagal function, which may increase the risk for cardiac mortality. Further studies are warranted to gain more insight into cardiac regulation in schizophrenia and the effect of novel antipsychotics.

*Department of Psychiatry and Psychotherapy, Friedrich-Schiller-University; †Department of Medical Engineering and Biotechnology, University of Applied Sciences, Jena, Germany; ‡Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI; and §Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada.

Received March 5, 2008; accepted after revision July 16, 2008.

Address correspondence and reprint requests to Karl-Jürgen Bär, MD, Department of Psychiatry, Friedrich-Schiller-University, Jena, Philosophenweg 3, 07743 Jena, Germany. E-mail: Karl-Juergen.Baer@med.uni-jena.de.

© 2008 Lippincott Williams & Wilkins, Inc.