Exposure to phenytoin associates with a lower risk of post-COVID cognitive deficits: a cohort study, 2022, Taquet and Harrison

Abstract

Post-COVID cognitive deficits (often referred to as ‘brain fog’) are common and have large impacts on patients’ level of functioning. No specific intervention exists to mitigate this burden.

This study tested the hypothesis, inspired by recent experimental research, that post-COVID cognitive deficits can be prevented by inhibiting receptor-interacting protein kinase. Using electronic health record data, we compared the cognitive outcomes of propensity score-matched cohorts of patients with epilepsy taking phenytoin (a commonly used receptor-interacting protein kinase inhibitor) versus valproate or levetiracetam at the time of COVID-19 diagnosis. Patients taking phenytoin at the time of COVID-19 were at a significantly lower risk of cognitive deficits in the 6 months after COVID-19 infection than a matched cohort of patients receiving levetiracetam (hazard ratio 0.78, 95% confidence interval 0.63–0.97, P = 0.024) or valproate (hazard ratio 0.73, 95% confidence interval 0.58–0.93, P = 0.011). In secondary analyses, results were robust when controlling for subtype of epilepsy, and showed specificity to cognitive deficits in that similar associations were not seen with other ‘long-COVID’ outcomes such as persistent breathlessness or pain. These findings provide pharmacoepidemiological support for the hypothesis that receptor-interacting protein kinase signaling is involved in post-COVID cognitive deficits. These results should prompt empirical investigations of receptor-interacting protein kinase inhibitors in the prevention of post-COVID cognitive deficits.

Open access, https://academic.oup.com/braincomms/article/4/4/fcac206/6668727

 

See here

https://www.s4me.info/threads/short-summary-of-meds-i-tried-by-now.15454/#post-265850

 

Interesting. It looks like a good attempt from the authors, but I didn't read the paper in depth; there is a helpful infographic following the abstract for anyone who can't read the entire paper. Fatigue is also analyzed as an outcome in the supplementary material but I wasn't sure how to read that table.

I didn't see me/cfs mentioned.

 

According to the supplement, the risk of developing fatigue on phenytoin was not significantly reduced compared to either levetiracetam or valproate.

 

The problem with this study, like with most studies of this type (epidemiological trawling through EHR), is that the definition of outcome is quite crude. Everyone here probably has brain fog but how many doctors will actually put down something so serious on your record:

Most ppl complaining of brain fog will probably be fobbed off with an ICD-10 diagnosis of nothing.