Clinical guidelines indicate that treatment with haloperidol, the most widely used antipsychotic drug, may be associated with increased cardiovascular mortality in patients with dementia.

To determine the cause of unexpected death in patients with dementia treated with haloperidol.

From January 1, 1989 through December 31, 2013, 1,219 patients with a primary diagnosis of dementia with behavioral disturbance were admitted to a 120-bed, free standing, psychiatric hospital. Sixty-five patients (5.3%) died unexpectedly. Complete post-mortem examinations after the unexpected death were performed in 55 patients, of whom 27 were treated with haloperidol, while the other received no antipsychotic drugs.

The leading causes of death were myocardial infarction (25.5% of patients), pneumonia (23.6%) and stroke (10.9%). Other causes of death were myocarditis (3.6%), airway obstruction (1.8%) and upper gastrointestinal bleeding (1.8%). The cause of death could not be established at autopsy in 18 (32.7%) patients, of whom 16 had significant myocardial fibrosis and 2 had metastatic malignancies. Compared with patients not treated with antipsychotics, the group receiving haloperidol comprised more patients who were 80 years of age or older (p=0.010) and/or had psychotic features (p=0.0095). The cardiovascular causes of death (i.e., myocardial infarction, stroke and myocarditis) was more common in the group not treated with haloperidol (p=0.034). All of the other autopsy findings were similar in the two groups.

Based on autopsy findings, treatment with haloperidol for dementia does not appear to be associated with increased risk of unexpected, lethal cardiovascular events.