Background Previous research suggests a link between antipsychotic use and stroke, but the relationships between receptor-binding profiles of antipsychotics and the risk of cerebrovascular events are unclear. Methods A total of 14,584 patients with incident stroke were enrolled in the National Health Insurance Research Database in Taiwan from 1998 to 2007. We conducted a case-crossover study to compare the rates of antipsychotic use. The effects of receptor-binding profiles of antipsychotics on stroke risk were estimated, while the moderating effects of age, sex, presence of dementia, and duration of antipsychotic treatment were evaluated by stratified analyses. Results The adjusted odds ratio of stroke risk with antipsychotics exposure was 1.60 (95% confidence interval, 1.51–1.69) using a 14-day time window. The use of antipsychotics with a high binding affinity of M1 muscarinic and α2 adrenergic receptors was associated with a greater risk of stroke than the use of other types of antipsychotics. An increased risk of stroke with antipsychotic use was noted in the patients who were older and/or who suffered from dementia. Moreover, our results showed that stroke risk with antipsychotic use was in a dose-related relationship. Conclusions Our findings suggest an association between stroke risk and high M1 muscarinic and α2 adrenergic affinity. The clinical implication is to start antipsychotics treatment at low dosages and to closely monitor the side effects in the initial treatment, particularly for individuals with older age and the presence of dementia.
