Sex Differences in Antipsychotic Related Metabolic Functioning in Schizophrenia Spectrum Disorders

The adverse metabolic risks associated with second generation antipsychotics (SGAs) are well known, and likely contribute to the high rate of premature mortality due to cardiovascular disease in schizophrenia. Female schizophrenia patients appear to be diagnosed with metabolic diseases at higher rates than males, which may reflect disparate adverse responses to SGAs. However, the relationship between sex, metabolic risk, and drug use is less developed. We aimed to explore this relationship further by identifying rates of metabolic disease in community dwelling schizophrenia patients by sex and SGA risk. Schizophrenia participants (N = 287, 40.4% female) were included in this analysis. Oneway-ANOVA and Fisher's Exact Test were used to compare groups, as appropriate, and Cohen's d was employed to estimate the effect size of sex. In the group as a whole, the rate of metabolic syndrome was higher than previously reported, but did not differ by sex. For females, greater metabolic disturbances across all medication risk groups were seen in BMI and waist circumference (p < 0.005) but most commonly in those receiving high risk medication (clozapine or olanzapine). Additionally, the number of participants receiving medications for these metabolic disturbances was extremely low (<30%). These results suggest that female schizophrenia patients taking clozapine or olanzapine represent a group at uniquely high risk for metabolic dysfunction and future adverse cardiovascular outcomes, and warrant close monitoring by clinicians to prevent worsening of metabolic risk through proper monitoring and interventions.

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Publication Details

Journal
Psychopharmacology Bulletin
Published
2025-08-12
DOI
https://doi.org/10.64719/pb.4358
Citations
53
Primary Topic
Schizophrenia research and treatment
Type
article
Field-Weighted Citation Impact
5.88
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article

Sex Differences in Antipsychotic Related Metabolic Functioning in Schizophrenia Spectrum Disorders

A. Zarina Kraal, Kristen M. Ward, Vicki L. Ellingrod
53 citations
Psychopharmacology Bulletin
Schizophrenia research and treatment
5.88
article

Sex Differences in Antipsychotic Related Metabolic Functioning in Schizophrenia Spectrum Disorders

A. Zarina Kraal, Kristen M. Ward, Vicki L. Ellingrod
article en
53 citations

Abstract

The adverse metabolic risks associated with second generation antipsychotics (SGAs) are well known, and likely contribute to the high rate of premature mortality due to cardiovascular disease in schizophrenia. Female schizophrenia patients appear to be diagnosed with metabolic diseases at higher rates than males, which may reflect disparate adverse responses to SGAs. However, the relationship between sex, metabolic risk, and drug use is less developed. We aimed to explore this relationship further by identifying rates of metabolic disease in community dwelling schizophrenia patients by sex and SGA risk. Schizophrenia participants (N = 287, 40.4% female) were included in this analysis. Oneway-ANOVA and Fisher's Exact Test were used to compare groups, as appropriate, and Cohen's d was employed to estimate the effect size of sex. In the group as a whole, the rate of metabolic syndrome was higher than previously reported, but did not differ by sex. For females, greater metabolic disturbances across all medication risk groups were seen in BMI and waist circumference (p < 0.005) but most commonly in those receiving high risk medication (clozapine or olanzapine). Additionally, the number of participants receiving medications for these metabolic disturbances was extremely low (<30%). These results suggest that female schizophrenia patients taking clozapine or olanzapine represent a group at uniquely high risk for metabolic dysfunction and future adverse cardiovascular outcomes, and warrant close monitoring by clinicians to prevent worsening of metabolic risk through proper monitoring and interventions.

Psychopharmacology BulletinVol. 47(2)
University of Michigan (US), Michigan Medicine (US)
Good health and well-being
Openalex Percentile: Top 5%
Schizophrenia research and treatment
5.88
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Sex Differences in Antipsychotic Related Metabolic Functioning in Schizophrenia Spectrum Disorders — A. Zarina Kraal, Kristen M. Ward, et al. · Psychopharmacology Bulletin (2025) | TGRS Research Map | TGRS