The antipsychotic risperidone
is associated with increased stoke risk in older adults with dementia,
even in those without cardiovascular disease (CVD), results of a large
population-based study showed.
“We knew that risperidone increased risk of stroke;
however, there were no major studies examining whether this risk
differed according to the clinical history of the patient,” co-first
author Byron Creese, PhD, Department of Psychology, Brunel University of
London, Uxbridge, England, told Medscape Medical News.
“We
found that the relative risk of stroke associated with risperidone was
the same across all subgroups. In this respect, we could say there is no
‘safer’ group to give risperidone to, at least when it comes to
clinical history,” Creese said.
The study was published online on October 9 in The British Journal of Psychiatry.
Similar Stroke Risk Across All Groups
Up to 50% of individuals living with dementia experience agitation or aggression
during the course of the illness. While nondrug interventions are
recommended as first-line treatment, antipsychotics such as risperidone
are often used when symptoms are severe.
Until now, little was known about risperidone influenced stroke risk in patients with and without a history of CVD.
To
find out, the researchers compared the incidence of stroke in adults
living with dementia who were prescribed risperidone with that of a
matched control group across subgroups of patients with and without a
prior history of stroke and other types of CVD.
Using the UK
Clinical Practice Research Datalink, they identified 28,403 older adults
who initiated risperidone after dementia diagnosis. Patients who had
received other antipsychotics within 90 days before being prescribed
risperidone were excluded as these medications also increase stroke
risk. Each risperidone user was propensity score-matched to up to five
control individuals with dementia who were not prescribed antipsychotics
(n = 136,324).
Risperidone was associated with an increased risk
for stroke in the overall cohort and in all subgroups over 1 year and in
a 12-week sensitivity analysis.
“The
principal new finding from this study was that relative risk of stroke
was comparable across all subgroups,” the investigators wrote.
In
the overall cohort, the unadjusted incidence rate of stroke (per 1000
person-years) was 53 in risperidone users vs 41 in control individuals.
In multivariable adjusted Cox models, risperidone users had a 28% higher
risk for stroke than matched control individuals (adjusted hazard ratio
[aHR], 1.28).
For risperidone users and matched control
individuals with a stroke history, the incidence rates for stroke were
222 and 177 per 1000 person-years, respectively (aHR, 1.23).
“Although
the relative risk of 1.23 may appear modest, a baseline 1-year risk of
177 per 1000 person-years is significant, and clinicians should be
mindful of prescribing a drug that increases stroke risk further in an
already at-risk group,” the authors wrote.
For
risperidone users and matched control individuals with no stroke
history, stroke incidence rates were 29 and 22 per 1000 person-years,
respectively, with an aHR of 1.34 — which was not statistically
different to that of the stroke history subgroup (aHR, 1.23).
“Therefore,
on average, a patient with stroke history has about the same relative
risk of stroke if prescribed risperidone as a patient with no stroke
history,” the authors noted.
Important New Evidence
Reached
for comment, Raya Elfadel Kheirbek, MD, MPH, professor of medicine, and
chief in the Division of Gerontology, Geriatrics, and Palliative
Medicine, University of Maryland School of Medicine, Baltimore, said
this large, real-world analysis provides “important new evidence to
guide antipsychotic prescribing in dementia, particularly in relation to
stroke risk.”
“While
prior studies have established an association between risperidone and
increased cerebrovascular events, this study offers novel insights by
stratifying risk across subgroups with and without preexisting CVD or
stroke,” Kheirbek told Medscape Medical News.
The findings, she said, “challenge the prevailing clinical assumption that heightened risk is largely confined to individuals
with prior stroke or CVD, and emphasizes that even patients perceived
as ‘low risk’ carry meaningful stroke risk with risperidone initiation,”
she said.
For clinicians, Kheirbek said, the study provides
“quantifiable, patient-relevant data to support more informed,
individualized discussions around risk.”
The
data can help “contextualize treatment decisions within each patient’s
clinical narrative, particularly when considering use in populations
already vulnerable to poor functional recovery after stroke,” Kheirbek
said. The data also underscore the importance of short-term vigilance:
risk was highest within the first 12 weeks of treatment, she noted.
“Overall,
the findings support a cautious, guideline-concordant approach to
risperidone prescribing — reserving it for severe symptoms that have not
responded to nonpharmacological strategies, and centering decisions on
both clinical evidence and patient/family priorities,” said Kheirbek.
Also
commenting on the findings Badr Ratnakaran, MBBS, chair of the American
Psychiatric Association Council on Geriatric Psychiatry said that the
link between antipsychotic use and a higher risk of cerebrovascular
events in older adults with dementia is already well recognized.
“Ideally,
treatment for agitation and psychosis in dementia should begin with
nonpharmacologic approaches,” said Ratnakaran, who was not involved in
the study.
“These include identifying potential sources of
distress, such as urinary infections, creating a calm environment, using
gentle redirection, soothing music, massage, aromatherapy, and
addressing sensory impairments.”
“However,
if nonpharmacological measures fail to control these symptoms or in
acute emergencies, antipsychotics can be used. Ideally, shared
decision-making with an explanation of the black box warning of
increased risk of mortality must be made with patients and/or their
caregivers about the judicious use of antipsychotics for the management
of behavioral and psychological symptoms of dementia,” Ratnakaran said.
“The American Psychiatric Association’s guidelines on the use of antipsychotics for the management of agitation in dementia
also support a patient-centered plan in using nonpharmacological and
pharmacological interventions, including antipsychotics,” Ratnakaran
added.
This study had no commercial funding. Creese declared
receiving consultancy fees from Milbotix Ltd and IGC Pharma. Kheirbek is
an associate editor of the Journal of Gerontology Medical Sciences.
Ratnakaran had no disclosures.
