Nausea medications known as antidopaminergic antiemetics (ADAs) are associated with an increased risk of ischaemic stroke.
The new study published by The BMJ found that nausea medications that are often used to relieve sickness and vomiting caused by instances such as migraine, chemotherapy, or radiotherapy and after surgery are linked with a heightened risk of ischaemic stroke.
Ischaemic strokes occur when a blockage in an artery leads to the brain and around 85% can be categorised as ischaemic. Strokes can cause lifelong problems such as cognition problems, fatigue and movement issues.
The impact of nausea medication on stroke risk
The researchers studied several nausea medications, including three ADAs (domperidone, metopimazine, and metoclopramide) and they found the link between an increased risk, especially in the first days of use, but the highest increase was found for metopimazine and metoclopramide nausea medications. The team of researchers suggested that the potential action of ADAs on blood flow to the brain could explain this higher risk.
Similar to antipsychotics, ADAs are antidopaminergic drugs – they work by blocking dopamine activity in the brain. Like the nausea medications, antipsychotics have been associated with an increased risk of ischaemic stroke, but whether this risk could extend to other antidopaminergics, including ADAs, is not known.
Estimating the risk of ischaemic stroke
To address this gap, the team of researchers in France from Inserm and Bordeaux University and Bordeaux CHU set out to estimate the risk of ischaemic stroke associated with ADA use in a real-world setting.
They identified 2,612 patients from the nationwide French reimbursement healthcare system database (SNDS) with a first ischaemic stroke between 2012 and 2016 and at least one reimbursement for nausea medications like domperidone, metopimazine or metoclopramide in the 70 days before their stroke. Patients had an average age of 72 years and 32% were men.
They compared frequencies of these ADA reimbursements between a risk period (days -14 to -1 before stroke) and three matched reference periods (days -70 to -57, -56 to -43, and -42 to -29 before stroke).
Patients with stroke were matched by age, sex and stroke risk factors to a healthy control group of 21,859 randomly selected people who also received nausea medications in the same period. Amongst patients with a stroke, 1,250 received an ADA nausea medication at least once in the risk period and 1,060 in the reference periods. Among the control group, 5,128 and 13,165 received an ADA at least once in the risk and reference periods, respectively.
After taking account of potentially influential factors, the researchers found that new users of ADA could be at a 3-fold increased risk of a stroke shortly after treatment started.
Further analyses by age, sex, and history of dementia showed similar results, with men at the highest (a 3.59-fold increased) risk.
The risk appeared to increase for all studied nausea medications, the highest increase being found for metopimazine (a 3.62-fold increase) and metoclopramide (a 3.53-fold increase), both of which are drugs that cross the blood-brain barrier.
This is an observational study, and as such, can’t establish cause, and the researchers pointed to some limitations that are inherent in database studies, such as a lack of information on prescribed daily dose or duration of ADAs and ischaemic stroke subtypes.
The researchers stated that their results show that the risk of ischaemic stroke appears to be associated with ADA use. And although further causal inference research is needed to confirm this association in other settings, they suggested that “the higher risk found for drugs crossing the blood-brain barrier suggests a potential central effect, possibly through an action on cerebral blood flow.”