Background: The efficacy of clozapine for the treatment of schizophrenia has been demonstrated. However, a
range of adverse events have been associated with its use. To date, there remains a paucity of data regarding the
prevalence of clozapine-induced cardiovascular (CV) and parameters associated with the development of metabolic
syndrome, alongside associated risk factors for their development.
Methods: An observational, clinical cohort study design of 355 clozapine patients who were enrolled in the Barwon
Health Clozapine Program at Geelong Hospital, Victoria, Australia, between 2008-12. Medical records were accessed
retrospectively. Multivariate logistic regression was used to determine associations with adverse event(s).
Results: Older age of commencement with clozapine was consistently associated with increased risk of CV abnormalities,
with the exception of tachycardia where older age was protective (Odds Ratio [OR]: 0.97; 95% Confidence Intervals [CI]:
0.95, 0.99). Males had significantly greater odds of most metabolic disturbances with the exception of being obese (BMI:
≥30 OR: 0.45; 95% CIs: 0.24, 0.85). Older age of commencement was a significantly associated variable with High-
Density Lipoprotein-cholesterol (OR: 1.03; 95% CIs: 1.01, 1.07) and fasting glucose (OR:1.04; 95% CIs: 1.02, 1.07). An
increase in BMI was consistently and significantly associated with all metabolic events.
Conclusion: Male patients who are obese at any point during treatment and older at treatment commencement may be the
most vulnerable to adverse CV and metabolic events. While future studies using a matched case-control design may be
required to verify these findings, we recommend that treating clinicians consider these risks when assessing patient
suitability to clozapine therapy.