Effects of olanzapine on resting heart rate in Japanese patients with schizophrenia

PLoS One. 2018 Jul 17;13(7):e0199922. doi: 10.1371/journal.pone.0199922. eCollection 2018.

Abstract

It has long been known that antipsychotic drugs (ATP) causes tachycardia, however details such as the differences between ATP are not well known. In recent years, the relationship between the rise in resting heart rate (RHR) and the increased risk of death in the general population has been garnering attention. In this study, we examined the difference in action on RHR between olanzapine (OLZ) and aripiprazole (ARP). The changes in the RHR on switching from OLZ to ARP and on increasing from the starting OLZ dose to the final one were evaluated in 19 outpatients (Study 1) and in 29 outpatients with schizophrenia (Study 2), respectively. To analyze the RHR, electrocardiographic measurements were obtained. At the same day, the Brief Psychiatric Rating Scale (BPRS) was evaluated, and fasting blood samples were drawn after an overnight fast of at least 8 h to examine electrolytes. Both Study 1 and 2 were conducted with the approval of the Gene Ethics Committee of Niigata University Graduate School of Medical and Dental Sciences, and the patients were treated at the outpatient psychiatric clinic at Niigata University Medical and Dental Hospital. All patients had been diagnosed with schizophrenia based on the DSM-IV-TR. In the Study 1, OLZ of 14.6 ± 9.2mg (mean ± standard deviation) was switched to ARP of 20.8 ± 8.1mg. Significant decreases were observed in the mean RHR after the switch to ARP (73.7 ± 9.7 vs 65.8 ± 10.9 beats/min, p = 0.008). In the Study 2, the starting OLZ dose was 7.2 ± 3.2mg and the increasing OLZ dose was 18.3 ± 7.4mg. Significant increases were observed in the mean RHR after increasing OLZ (69.7 ± 14.0 vs 75.6 ± 14.3 beats/min, p = 0.004). In this study, it was shown that OLZ has a stronger RHR enhancing effect compared to ARP and its effects are dose-dependent. If the increase in RHR increases the mortality rate of patients with schizophrenia, it may be necessary to further investigate the differences between ATP in terms of the effect on RHR of second-generation antipsychotics with a strong anticholinergic action or phenothiazine antipsychotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Heart Rate / drug effects*
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Olanzapine / adverse effects*
  • Olanzapine / therapeutic use
  • Rest / physiology*
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Young Adult

Substances

  • Antipsychotic Agents
  • Olanzapine

Grants and funding

The study was funded by a Grants-in-Aid for Scientific Research (Kakenhi) from the Japan Society for the Promotion of Research (JSPS, #17591199 and #19591344), Mitsubishi Pharma Research Foundation and Health and Labour Sciences Research Grants (Research on Psychiatric and Neurological Diseases and Mental Health, H17-kokoro-002) to Toshiyuki Someya, and a Grant-in-Aid for Scientific Research (Kakenhi) from JSPS (#20591362) to Yutaro Suzuki. The funding sources played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. The other authors have no sources of funding.