Effects of Cigarette Smoking and Clozapine Treatment on 20-Year All-Cause & Cardiovascular Mortality in Schizophrenia

  • Patrick A. Stolz
  • Heidi J. WehringEmail author
  • Fang Liu
  • Raymond C. Love
  • Marcus Ellis
  • Bethany A. DiPaula
  • Deanna L. Kelly
Original Paper


To estimate 20-year mortality risk in people with schizophrenia treated with second-generation antipsychotics (SGA) and examine the effects of cigarette smoking on mortality. Of the 1199 individuals with schizophrenia in the study, estimated 20-year all-cause mortality risk by Kaplan Meier Curve was 30% and leading causes of death included 27% cardiovascular disease, 13% cancer, 12% non-HIV infection, 5% respiratory causes, 20% other causes and 18% had unknown cause of death. For all-cause mortality, we found that white race and male sex were significant risk factors (HR = 1.5, p = 0.002 and HR = 1.33, p = 0.033, respectively). For cardiovascular mortality risk, we showed that cigarette smokers and white race were at higher risk (HR = 1.86, p = 0.017 and HR = 1.71, p = 0.045, respectively). Cardiovascular mortality risk at 20-years is 11%. Kaplan-Meier Survival Curve showed a statistical difference for smokers and non-smokers in cardiovascular mortality over the 20-year follow-up (Log rank chi-square = 5.35, df = 1, p = 0.02). 20-year all-cause mortality risk for individuals with schizophrenia was found to be 30% with cardiovascular disease as a leading cause. Cigarette smokers and white race were associated with an increased risk of death. Regarding cardiovascular mortality specifically, cigarette smoking increased risk by 86% over a 20-year period. Clozapine was neither a risk factor for all-neither cause nor cardiovascular mortality. This data suggests that long-term cardiovascular mortality continues to be increased in schizophrenia for those who are or have been cigarette smokers.


Schizophrenia Mortality Clozapine Cigarette Smoking Cardiovascular 



We would like to thank and acknowledge those who helped create the database and have worked on this project historically. We thank Robert R Conley, Kristen Mackowick, and Robert P. McMahon.


This study was funded in part by National Institute of Mental Health R01(MH102215) (Kelly, PI) and by National Institute on Drug Abuse K23(DA034034-01A1) (Wehring, PI).

Compliance with Ethical Standards

Conflict of Interest

Deanna L. Kelly: Advisory board for Lundbeck and a consultant for HLS Therapeutics.

Raymond C. Love: Speaking fee for Nevada Psychiatric Association, received honorarium for Advisory Board on Pharmacist Administration of Medication, and is part of the National Alliance of State Pharmacy Association.

All other authors declare they have no conflicts of interest.

Ethical Approval

All procedures performed were done so in accordance with the ethical standards of the University of Maryland and Maryland Department of Health Institutional Review Boards and with the 1964 Helsinki declaration and its later amendments.

Informed Consent

A waiver of informed consent was approved by the University of Maryland-Baltimore and the Maryland Department of Health Institutional Review Boards for this retrospective study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.University of Maryland School of PharmacyBaltimoreUSA
  2. 2.Maryland Psychiatric Research CenterUniversity of Maryland Baltimore School of MedicineCatonsvilleUSA

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