In a new study of patients at least 65 years old hospitalized with COVID-19, researchers found that those who took psychiatric drugs were more than three times as likely to receive a dementia diagnosis within one year. According to the researchers, the results were unique to psychiatric drug use, not driven by underlying mental health conditions.
“Prior use of antipsychotics, antidepressants, benzodiazepines and mood stabilizers/anticonvulsants, were significantly associated with a higher risk of incident post-COVID dementia.”
The study was published in Frontiers in Medicine. It included 1,755 patients at least 65 years old hospitalized with COVID-19. Dementia occurred in 12.7% of the participants over the next year. Those who had previously taken psychiatric drugs were 3.2 times more likely to receive a dementia diagnosis.
But this result could have been driven by the underlying psychiatric diagnosis and not the drugs. So the researchers did a second analysis of only the 423 participants who had a psychiatric diagnosis to account for this. If dementia were linked to underlying mental health and not psychiatric drugs, we would expect to see no (or very little) difference between those who took psychiatric drugs versus those who did not in this smaller group.
Instead, the researchers found that psychiatric drugs still raised dementia risk threefold. Among only those with a psychiatric diagnosis, those who took psychiatric drugs were still 3.09 times more likely to receive a diagnosis of dementia than their peers.
Some of the commonly used drugs that were associated with extremely high risk included valproic acid/valproate (11.57 times more likely to receive a dementia diagnosis); haloperidol/Haldol (8.44 times more likely); mirtazapine/Remeron (6.02 times more likely); levetiracetam/Keppra (5.91 times more likely); clonazepam/Klonopin (3.97 times more likely); quetiapine/Seroquel (3.9 times more likely); and escitalopram/Lexapro (3.49 times more likely).
The researchers then did two tests called Random Forest (which uses machine learning) and LASSO regression, both of which are designed to check again whether this result was true. Again, both of these tests confirmed the effect.
This is not the first time these drugs have been found to increase dementia. Antipsychotics have been found to increase the risk of dementia, as have antidepressants and benzodiazepines. Researchers in 2016 found that valproic acid/valproate increased dementia risk in people with a bipolar diagnosis. A 2018 study found that those who used antiepileptic drugs—like levetiracetam/Keppra—also had a higher risk of dementia.
Oddly, despite their multiple tests using documented psychiatric diagnoses to confirm that the effect was due to the drugs, the researchers still suggest that the drugs may be “risk markers that signify neuropsychiatric symptoms” but admit that they likely also “contribute to post-COVID dementia.”
The authors’ financial conflicts of interest with the pharmaceutical industry are listed below:
Consulting fees, payments, honoraria, or support for attending meetings: MC: Board fee from Haven Behavioral Health Care Board; SUNY Downstate School of Medicine Department of Medicine Grand Rounds; Maimonides Medical Center Department of Medicine Grand Rounds; Board of Governors of American College of Physicians 2018–2021 meetings; JK: Consultant to or receives honoraria: Alkermes, Allergan, Dainippon Sumitomo, H. Lundbeck, Indivior, Intracellular Therapies, Janssen Pharmaceutical, Johnson & Johnson, LB Pharmaceuticals, Merck, Minerva, Neurocrine, Novartis Pharmaceuticals, Otsuka, Reviva, Roche, Saladex, Sunovion, Takeda, Teva Grant Support: Otsuka, Lundbeck, Sunovion, Vanguard Research Group LB Pharmaceuticals, and North Shore Therapeutics; Participation on Data Safety Monitoring Board or Advisory Board: JK: Teva and Novartis; EB: PCORI Eugene Washington Award advisory panel member. Leadership or fiduciary role: MD: Society of Behavioral Medicine, President and past President (unpaid). EB: Society of Behavioral Medicine: nominating committee; annual program committee (unpaid). Associate editor, Translational Behavioral Medicine (unpaid). Stock or stock options: YF-H co-owns stock and stock options from Regeneron Pharmaceuticals.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Freudenberg-Hua, Y., Makhnevich, A., Li, W., Liu, Y., Qiu, M., Marziliano, A., . . . & Sinvani, L. (2022). Psychotropic medication use is associated with greater 1-year incidence of dementia after COVID-19 hospitalization. Frontiers in Medicine. https://doi.org/10.3389/fmed.2022.841326 (Link)