Effects of antipsychotic medication on cardiovascular function and fitness in individuals with schizophrenia

Background: Individuals living with schizophrenia have consistently demonstrated impaired cardiovascular fitness. It is of particular interest whether antipsychotic medications significantly contribute to the reduced cardiovascular fitness in these individuals. A comprehensive review of the literature and meta-analysis was performed to examine the overall dose-dependent effect of antipsychotics on cardiovascular fitness. Also, it was tested in our participants with schizophrenia whether this dose-dependent effect might be independent of body mass index (BMI) and whether cardiovascular fitness might be further reduced in those exposed primarily to clozapine versus other antipsychotics. Methods: For our comprehensive review and meta-analysis, an electronic search of the literature was performed to identify studies that examined the effects of antipsychotics on cardiovascular fitness. For our original research investigation, 30 participants with schizophrenia or schizoaffective disorder stabilized on antipsychotics were recruited. The patients were divided into the clozapine (n = 15) and non-clozapine (n = 15) groups, and a group of healthy age- and sex-matched controls (n = 15) was included. All current antipsychotic doses were converted to chlorpromazine equivalents (CPZE). Each participant completed maximal symptom-limited exercise testing on a cycle ergometer for the assessment of peak aerobic power (VO₂peak). Results: The meta-analysis revealed an overall significant dose-dependent effect of antipsychotics on cardiovascular fitness in a total of 294 participants (correlation coefficient: -0.29, 95% CI: -0.43 to -0.14, p < 0.001). In our patients, after controlling for BMI, every 100-mg⋅d-¹ increase in CPZE was associated with approximately a 1-mL⋅kg-¹⋅min-¹ reduction in VO₂peak (p = 0.046). Moreover, the clozapine group demonstrated further reduced VO₂peak as compared to the non-clozapine group, even after controlling for BMI and CPZE (p = 0.042). Conclusion: In conclusion, antipsychotics affect cardiovascular fitness in a dose-dependent manner, and this effect is independent of BMI in individuals with schizophrenia. Also, those receiving clozapine have further reduced cardiovascular fitness than those receiving other antipsychotics. Potential mechanisms are not clear, but it is suggested that altered activity of peripheral adrenergic and muscarinic receptors, as well as altered metabolism, by antipsychotics may contribute to the impaired cardiovascular fitness in individuals with schizophrenia.Medicine, Faculty ofExperimental Medicine, Division ofMedicine, Department ofGraduat