Previous observational studies have found an increased risk of stroke with centrally acting antidopaminergic antipsychotics, especially in older patients and among those with dementia.
The risk is considerable at the start of the treatment, 12 times higher in the first month of use, and then declines over time, falling to baseline after three months of treatment.
Studies are lacking on the risk of stroke for non-antipsychotic dopamine receptor antagonists, such as antidopaminergic antiemetics (ADAs), which are peripheral D2 receptor antagonists with a direct effect on the chemoreceptor trigger zone, and some of them can cross the blood-brain-barrier, like metoclopramide.
In a recently published study, researchers from Bordeaux University INSERM, Sorbonne Université, and CHU de Bordeaux evaluated the use of ADAs and the risk of ischemic stroke. The results appear in the BMJ.
Study Development and Results
The team used data from 2,612 adults from the French reimbursement healthcare system database between 2012 and 2016. Eligible participants were ≥18 years with a first ischaemic stroke between 2012 and 2016 and at least one reimbursement for any ADA in the 70 days before stroke. The average age of participants was 71.9 years.
The study identified 3 ADAs, domperidone, metoclopramide, and metopimazine. The researchers then compared participants with a control group of 21,859 randomly selected participants without ischemic stroke.
Overall the team found that those participants who received metopimazine had an increased stroke risk 3.62 times, metoclopramide 3.53 times, and domperidone 2.51 times.
The results raise the question if the risk outweighs the benefit of these medications, and whether it might be wise to use other types of antiemetics instead.
Anne Bénard-Laribière, et al. Risk of first ischaemic stroke and use of antidopaminergic antiemetics: nationwide case-time-control study. 2022. BMJ. doi: 10.1136/bmj-2021-066192.