1. There was a moderate association found between antipsychotic use and acute ischemic heart disease found in women, but not men.
Evidence Rating Level: 2 (Good)
The use of antipsychotic medications is increasing worldwide and is not limited to treating indications such as psychotic and bipolar disorder; up to 60% of prescriptions are written for off-label use treatment of anxiety, depression, dementia, sleep, and personality disorders. Studies have shown that metabolic abnormalities associated with long-term use of antipsychotics, such as weight gain, glucose intolerance, and dyslipidemia, lead to an increased risk of diabetes, cardiovascular disease, and mortality in this population. Growing evidence supports that there are differences in how women and men develop cardiovascular diseases, as well as in prevalence rates of risk factors (sedentary lifestyle, alcohol and tobacco use). However, sex difference in the association between antipsychotic use and ischemic heart disease (IHD) is poorly studied. In this retrospective cohort study, health records from 1 043 262 patients in the Hong Kong primary care population over 45 years of age were examined. 17 780 (1.7%) were prescribed antipsychotics within the last 12 months and 8 324 (0.8%) developed IHD. A mixed-effects Cox model was used to examine hazard ratios of acute hospitalization secondary to IHD comparing patients on antipsychotics and those without, while adjusting for confounders such as baseline morbidities, tobacco abuse, antidepressant and statin prescriptions. Antipsychotics were associated with an increased hazard rate of acute IHD among women (HR 1.32, 95% CI 1.05-1.67) but not among men. This result was further supported by a sex-combined model, with a likelihood ratio test suggesting significant interaction between antipsychotic use and sex (chi square = 4.72, p=0.030). Moreover, the sensitivity analysis showed that, after replicating the main analysis and omitting one out of sixteen antipsychotics each time, the hazard ratios for antipsychotic use among women stayed similar except in the analysis where haloperidol was omitted (HR: 1.23, 95% CI 0.96-1.60). This suggests use of haloperidol may underlie this sex difference. While this study showed a moderate association specific to females in antipsychotic use and IHD, further studies should investigate a potential dose-effect relationship while implementing randomization procedures to isolate the independent effect of the antipsychotics.
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