Antiemetics linked to increased risk of stroke

Antidopaminergic antiemetics are associated with an increased risk of ischaemic stroke, an observational study has shown.

Fusion image of MRA of cerebral artery in the brain.
Domperidone and metoclopramide are peripherally acting drugs but metoclopramide also crosses the blood brain barrier and acts centrally. | GETTY IMAGES

The risk of ischaemic stroke with centrally acting antidopaminergic antipsychotics has been highlighed in many large observational studies, but there is a lack of research on the risk of stroke for non-antipsychotic antidopaminergic drugs such as domperidone and metoclopramide, which are widely used for the treatment of nausea and vomiting. A study published in the BMJ now shows there is a link between these drugs and stroke. 

Study design

Using data from the nationwide French reimbursement heathcare system database Système National des Données de Santé, researchers conducted a case-time-control study to evaluate the risk of ischaemic stroke associated with the use of antidopaminergic antiemetics (ADAs) in adults. 

Researchers identified 2612 patients who had an ischaemic stroke between 2012 and 2016 and at least one reimbursement for domperidone, metopimazine (not licensed in the UK) or metoclopramide in the 70 days before their stroke. These patients were matched according to age, gender and risk factors for stroke to a healthy control group of 21,859 patients who also received one of the three ADAs in the same time period. 

Among the 2612 patients identified with stroke, 1250 received an ADA in the risk period (days -14 to -1 before stroke) and 1060 in the reference periods (days -70 to -57, -56 to -43, and -42 to -29 before stroke). The comparison with the 5128 and 13,165 controls who received an ADA in the same periods yielded a ratio of adjusted odds ratios of 3.12 (95% CI 2.85–3.42).

Although the study showed the risk of stroke increased with all three ADAs, of the two licensed in the UK, the highest increase was for metoclopramide, with a ratio of adjusted odds ratios of 3.53 (95% CI 2.62–4.76) compared with a ratio of 2.51 for domperidone (95% CI 2.18–2.88). Researchers suggest this could be due to metoclopramide crossing the blood-brain barrier causing a central effect, possibly through an action on cerebral blood flow. 

A sensitivity analysis that used risk and reference periods of 7 days showed a higher risk of 4.66 (95% CI 4.14–5.25) compared to a period of 21 days which showed a lower risk of 2.59 (95% CI 2.37–2.82), suggesting the risk would be higher in the first few days of ADA use. 

Although the researchers see a clear link between the increased risk of stroke and ADA use, they acknowledge this was an observational study with limitations and say further research is needed to confirm the association. 

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