Common anti-nausea drugs linked to stroke risk in new study - Medical News Today

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A new study of participants aged 71.9 years, on average, found a link between the use of anti-nausea medication and increased stroke risk. Gary John Norman/Getty Images

• A recent study found that certain anti-nausea and vomiting medications tripled the risk for ischemic stroke.
• The risk was highest for metopimazine, followed by metoclopramide, and then domperidone.
• More studies are needed to confirm the findings.

Providers may use antipsychotic medications to treat conditions such as schizophrenia, psychotic depression, bipolar disorder, and dementia, which cause symptoms of psychosis or losing touch with reality. Excess dopamine may play a role in psychosis.

Dopamine is a chemical messenger or neurotransmitter that influences mood, feelings of reward, and movement. Antipsychotics work by blocking dopamine receptors in the brain, which causes a decrease in dopamine levels.

There is an association between antipsychotic use and dementia in older adults and an increased risk for ischemic stroke or a blood clot blocking blood flow in the brain. Data from these studies led the United States Food and Drug Administration (FDA) to issue a black box warning to warn older people with dementia of the increased risk of death with antipsychotic use.

Other medications to treat nausea and vomiting associated with chemotherapy or migraine also block dopamine receptors or antidopaminergic antiemetics (ADA). ADAs block dopamine transmission to the intestines and the chemoreceptor trigger zone in the brain, responsible for relaying signals causing vomiting.

This led French-based researchers from Bordeaux University INSERM, Sorbonne Université, INSERM, and CHU de Bordeaux to evaluate if ADA use increases the risk of ischemic stroke.

They published their findings in The BMJ.

Researchers examined data from 2,612 adults from the French reimbursement healthcare system database between 2012 and 2016. Participants included in the study experienced an initial ischemic stroke and received reimbursement for one or more ADA(s) within 70 days before the stroke.

The researchers used reimbursements — to reflect the payment received for the treatment — as a measure of treatments administered.

The study identified 3 ADAs: domperidone, metoclopramide, and metopimazine. Domperidone and metopimazine are not approved for use to treat nausea and vomiting in the United States by the FDA.

Researchers assessed the frequency of ADA for reimbursement for each participant on days 1–14 before stroke (risk period) and days 29–42, 43–56, and 57 to 70 before stroke (reference periods).

Researchers compared participant data to a control group of 21,859 randomly selected participants who did not experience an ischemic stroke. The study matched control group participants to participants with strokes by age, sex, and ischemic stroke risk factors.

The average age of participants included in the study was 71.9 years old, and approximately one-third were men. About 97% of those who had an ischemic stroke received one ADA medication.

The study found that participants receiving ADAs overall had a 3.12 times greater risk for ischemic stroke than the control group after adjusting for medications that may affect ischemic stroke risk.

Metopimazine significantly increased ischemic stroke risk 3.62 times, metoclopramide 3.53 times, and domperidone 2.51 times.

Metopimazine and metoclopramide cross the blood-brain barrier, which controls the movement of substances from the blood to the brain. However, domperidone does not.

Sensitivity analyses indicate that ischemic stroke risk is highest 7 days before the ischemic stroke. Sensitivity analysis is a method to determine the strength of effects seen in a study which lends credibility to the findings.

Dr. Anne Bénard-Laribière, PharmD, MSc at the University of Bordeaux Population Health and study co-author, spoke to Medical News Today.

"The publication raises a strong signal associating the use of antiemetics to an increased risk of ischemic stroke," she said. "Right now, as this is the first study evidencing such risk, replication will be needed to confirm and strengthen the already robust findings, and ideally provide complementary information on mechanisms and risk factors."

Dr. Walavan Sivakumar, M.D., board certified neurosurgeon and director of neurovascular surgery at Pacific Neuroscience Institute at Providence Saint John's Health Center in Santa Monica, CA, commented to MNT, "[T]his was a well-done study […] using a consistent database that afforded very reliable data [removing] different sources of bias."

Dr. Bénard-Laribière added, "The design we used allows self-controlling for most of [the] confounding — as the [participant] is [their] own control, so the results cannot be affected by any differences across compared [participants] in terms of genetics, for instance. The price to pay for this control with this design is the lack of possibility to provide absolute risks."

The study did not examine other ADAs marketed in the U.S., such as prochlorperazine, promethazine, and chlorpromazine.

"Making inferences based on these results related to the specific drugs is going to be very challenging. […] There are other [ADAs] that are used that still may be okay and need to be specifically studied before making any clear recommendations."

– Dr. Sivakumar

Dr. Sivakumar also stated that these results only apply to risk for ischemic strokes and not hemorrhagic ones, which involve bleeding in the brain.

Dr. Bénard-Laribière commented, "ADAs [use has] known risks of serious adverse effects (ventricular arrhythmia), frequent adverse effects (dyskinesia, other extrapyramidal disorders) to which this study adds a strong signal for the risk of ischemic stroke."

She added that the benefits of the ADAs might outweigh the risks to prevent serious nausea/vomiting complications. Still, the symptomatic treatment of mild nausea may warrant other therapy.

Dr. Bénard-Laribière stated, "As for all drugs, use only when medically needed is one of the best first mitigation [measures] for known risks and potential ones."