Psychotropic Med Use Tied to 'Striking'
Post-COVID Dementia Risk

Megan Brooks

March 29, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Older adults taking psychotropic medication before contracting COVID-19 are at increased risk dementia in the year following the illness, new research suggests.

Results from a large study of more than 1700 patients who had been hospitalized with COVID showed a greater than twofold increased risk for post-COVID dementia in those taking antipsychotics and mood stabilizers/anticonvulsants — medications often used to treat schizophrenia, psychosis, bipolar disorder, and seizures.

Dr Liron Sinvani

"We know that preexisting psychiatric illness is associated with poor COVID-19 outcomes, but our study is the first to show an association with certain psychiatric medications and dementia," co-investigator Liron Sinvani, MD, The Feinstein Institutes for Medical Research, Manhasset, New York, told Medscape Medical News.

"Our study highlights the potential interaction between baseline neuropsychiatric disease, psychotropic medications, COVID-19, and dementia," Sinvani added.

The findings were published online March 18 in Frontiers in Medicine.

"Striking" Dementia Rate

Using electronic health records, the researchers evaluated pre-COVID psychotropic medication use and post-COVID dementia onset in 1755 adults aged 65 and older. All were hospitalized with COVID-19 at Northwell Health between March 1 and April 20, 2020.

A "striking" 13% of the participants (n = 223) developed dementia within 1-year of follow-up, the investigators report.

Among the 438 patients (25%) exposed to at least one psychotropic medication before COVID-19, 105 (24%) developed dementia in the year following COVID vs 118 of 1317 (9%) patients with no pre-COVID exposure to psychotropic medication (odds ratio [OR], 3.2; 95% CI, 2.37 - 4.32).

Both pre-COVID psychotropic medication use (OR, 2.7; 95% CI, 1.8 - 4.0, P < .001) and delirium (OR, 3.0; 95% CI, 1.9 - 4.6, P < .001) were significantly associated with post-COVID dementia at 1 year.

In a sensitivity analysis in the subset of 423 patients with at least one documented neurologic or psychiatric diagnosis at the time of COVID admission, and after adjusting for confounding factors, pre-COVID psychotropic medication use remained significantly linked to post-COVID dementia onset (OR, 3.09; 95% CI, 1.5 - 6.6, P = .002).

Drug classes most strongly associated with 1-year post-COVID dementia onset were antipsychotics (OR, 2.8, 95% CI, 1.7 - 4.4, P < .001) and mood stabilizers/anticonvulsants (OR, 2.4, 95% CI, 1.39 - 4.02, P = .001).

In a further exploratory analysis, the psychotropics valproic acid (multiple brands) and haloperidol (Haldol) had the largest association with post-COVID dementia.

Antidepressants as a class were not associated with post-COVID dementia, but the potential effects of two commonly prescribed antidepressants in older adults, mirtazapine (Remeron) and escitalopram (Lexapro), "warrant further investigation," the researchers note.

Predictive Risk Marker?

"This research shows that psychotropic medications can be considered a predictive risk marker for post-COVID dementia. In patients taking psychotropic medications, COVID-19 could have accelerated progression of dementia after hospitalization," lead author Yun Freudenberg-Hua, MD, the Feinstein Institutes, said in a news release.

It is unclear why psychotropic medications may raise the risk for dementia onset after COVID, the investigators note

"It is intuitive that psychotropic medications indicate preexisting neuropsychiatric conditions in which COVID-19 occurs. It is possible that psychotropic medications may potentiate the neurostructural changes that have been found in the brain of those who have recovered from COVID-19," they write.

The sensitivity analysis in patients with documented neurologic and psychiatric diagnoses supports this interpretation. 

COVID-19 may also accelerate the underlying brain disorders for which psychotropic medications were prescribed, leading to the greater incidence of post-COVID dementia, the researchers write.

"It is important to note that this study is no way recommending people should stop taking antipsychotics, but simply that clinicians need to factor in a patient's medication history while considering post-COVID aftereffects," Freudenberg-Hua said.

"Given that the number of patients with dementia is projected to triple in the next 30 years, these findings have significant public health implications," Sinvani added.

She noted that "care partners and healthcare professionals" should look for early signs of dementia, such as forgetfulness and depressive symptoms, in their patients.

"Future studies must continue to evaluate these associations, which are key for potential future interventions to prevent dementia," Sinvani said.

The study was funded by the National Institutes of Health. Freudenberg-Hua co-owns stock and stock options from Regeneron Pharmaceuticals. Sinvani has disclosed no relevant financial relationships.

Front Med. Published online March 18, 2022. Full text

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