Wang, GHM; Man, KKC; Chang, WH; Liao, TC; Lai, ECC; (2021) Use of Antipsychotic Medications and Cholinesterase Inhibitors and the Risk of Falls and Fractures: self-controlled case series. The British Medical Journal (In press).

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Abstract

Objective: To evaluate the association between the use of antipsychotic medications and cholinesterase inhibitors, and the risk of falls and fractures in elderly patients with major neurocognitive disorders. / Design: Self-controlled case series / Setting: Taiwan’s National Health Insurance Database / Participants: 15,278 patients who were aged 65 or older, were newly prescribed antipsychotic medications and cholinesterase inhibitors, and suffered an incident fall or fracture between 2006 and 2017. Prescription records of cholinesterase inhibitors were used to confirm the diagnosis of major neurocognitive disorders since all use of cholinesterase inhibitors was subject to review by experts based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and patients’ scores of Mini-Mental State Examination. We excluded those with schizophrenia and bipolar disorder before the first prescription of cholinesterase inhibitors to ensure that antipsychotic medications were used for neuropsychiatric symptoms of major neurocognitive disorders. / Main outcome measures: We used conditional Poisson regression to derive the incidence rate ratio and the 95% confidence interval for evaluating the association between the risk of falls and fractures and different exposure periods, including cholinesterase inhibitors alone, antipsychotic medications alone, and combination, as compared with the non-exposure period for the same individual. Moreover, we defined a 14-day pre-exposure period before study drug initiation over concerns about confounding by indication. / Results: Compared with the non-exposure period (incidence rate per 100 person-years; 95% confidence interval: 8.30; 8.14 to 8.46), the highest risk of falls and fractures occurred during the pre-exposure period (52.35; 48.46 to 56.47), followed by combination (10.55; 9.98 to 11.14), antipsychotic medications alone (10.34; 9.80 to 10.89), and cholinesterase inhibitors alone (9.41; 8.98 to 9.86). Conclusions: The incidence of falls and fractures was especially high in the pre-exposure period, suggesting that factors other than the study medications, such as underlying diseases, should be taken into consideration when evaluating the association between the risk of falls and fractures, and the use of cholinesterase inhibitors and antipsychotic medications. The exposure periods were also associated with a higher risk of falls and fractures, compared with the non-exposure period, although the magnitude was much lower than during the pre-exposure period. Prevention strategies and close monitoring of the risk of falls are still necessary until there is evidence that patients have regained a steady status.

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