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Antipsychotics tied to increased MI risk in demented patients

NEW YORK (Reuters Health) – Older patients with treated dementia have a modestly increased risk of myocardial infarction in their first few weeks on antipsychotic therapy, according to a retrospective cohort study.

While more study is needed to determine if the relationship is truly causal, the bottom line for clinicians should be that these medications are risky for older patients with dementia, Dr. Sudeep Gill of Queen’s University in Kingston, Ontario, told Reuters Health.

“In elderly patients with dementia, if we can minimize their use, that’s really the thing we want to do,” added Dr. Gill, who co-authored a commentary on the study.

Ever since 2005, when a meta-analysis by Dr. Lon Schneider and colleagues found an increased risk of death in patients with dementia treated with atypical antipsychotics, investigators have been trying to pin down how these medications might harm patients, and whether some might be less risky than others. Studies have since linked both atypical antipsychotics and older antipsychotic medications to an increased risk of ischemic stroke.

In the current study, Dr. Antoine Pariente, then at the University of Montreal, and his colleagues looked at whether antipsychotics would be associated with increased risk of acute myocardial infarction in patients already taking cholinesterase inhibitors to treat dementia.

As reported online March 26 in the Archives of Internal Medicine, the researchers used the Quebec provincial prescription claims database to identify 37,138 older, community-dwelling patients who started taking cholinesterase inhibitors between 2000 and 2009. This group included 10,969 patients (29.5%) who started taking an antipsychotic during the study period. The researchers compared the risk of incident MI for these patients and a random sample of 10,969 patients who were not taking antipsychotics.

In the first year after antipsychotic initiation, 1.3% of patients exposed to the drugs and 1.2% of the control group had an incident MI. Multivariate analysis found the hazard ratio for MI among antipsychotic users to be 2.19 for the first 30 days of treatment, 1.62 for the first 60 days, 1.36 for the first 90 days, and 1.15 for the first year. Results were similar using propensity score-adjusted models.

There is still no biological explanation for how antipsychotics might increase heart attack risk in patients with dementia, Dr. Pariente told Reuters Health. Nevertheless, he added, clinicians should consider alternatives when possible, and if they must prescribe antipsychotics to patients with dementia, monitor these patients carefully during the early weeks of treatment, especially if they are already at increased risk for cardiovascular disease.

“There are some alternatives for moderate behavior disorders, but once there is a really strong behavioral disorder or delusion or psychotic-like symptoms in the demented, it’s clear that antipsychotics are really the worst and the best choice to make, and so there is not really an alternative,” added Dr. Pariente, who is now with the University Bordeaux Segalen in France.

In their commentary, Dr. Gill and his colleague Dr. Dallas P. Seitz point out that studies of antipsychotics and heart attack risk have had conflicting results, and there is still no biologically plausible mechanism to explain any association. However, they add, there is better evidence for other ways that the drugs cause harm, for example by increasing the risk of aspiration via their sedating effects and by contributing to QT interval prolongation and ventricular arrhythmias.

“Physicians should limit prescribing of antipsychotic drugs to patients with dementia and instead use other techniques when available, such as environmental and behavioral strategies, to keep these patients safe and engaged,” the editorialists conclude.

Despite the known risks of antipsychotics for patients with dementia, Dr. Gill noted in an interview, “part of the reason that clinicians persist in using them is we don’t have really highly effective alternatives, so we end up kind of using these somewhat toxic drugs because I think clinicians feel there are limited alternatives.”

Antipsychotics are most valuable for treating patients with true psychotic symptoms, such as seeing threatening figures and hearing threatening voices, Dr. Gill added. However, he said, these drugs are frequently prescribed for other symptoms, such as general agitation. “In that setting,” he said, “antipsychotics can work because they are highly sedating medications, the tradeoff is that that sedation may result in an increased risk of falling and fall-related injuries, and may lead to aspiration.”

A better approach to treating demented patients with generalized agitation, according to Dr. Gill, is ABC charting, which involves identifying possible antecedents to the behavior, as well as the consequences of the behavior for the patient and others. “ABC charting and other approaches really do emphasize the importance of recognizing that behaviors do not occur in isolation, and that knee-jerk whipping out the prescription pad is not the appropriate response,” he said.


Arch Intern Med 2012.