Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for...cognitive deficits in Long-COVID, 2022, Fesharaki-Zadeh

The article is from the Yale School of Medicine.
https://medicine.yale.edu/news-arti...l&utm_campaign=YT_YaleToday-Public_12-15-2022

Here's a excerpt, more at link.

Potential New Treatment for “Brain Fog” in Long COVID Patients
December 13, 2022
by Isabella Backman
While the number of patients they studied is too small for their results to be definitive, Yale researchers—using their extensive experience with two existing medications—have published initial evidence that those drugs, given together, can mitigate or even eliminate brain fog.

Guanfacine, developed in the lab of Amy Arnsten, PhD, Albert E. Kent Professor of Neuroscience and professor of psychology, was approved by the Food and Drug Administration (FDA) for the treatment of ADHD in 2009, but clinicians have also used it extensively off-label for other prefrontal cortical disorders such as traumatic brain injury (TBI) and PTSD. Now, Arnsten has joined forces with Arman Fesharaki-Zadeh, MD, PhD, assistant professor of psychiatry and of neurology, who has been treating long COVID patients with a combination of guanfacine and N-acetylcysteine (NAC), an anti-oxidant also used for the treatment of TBI. The combined therapy, they found, was successful in relieving brain fog for their small cohort of patients. And while larger, placebo-controlled clinical trials will be needed to establish these drugs as a bona fide treatment for post-COVID-19 neurocognitive deficits, they say patients can obtain them now if their doctors wish to prescribe them.

 

I think the fact that this is already established treatment for post concussion patients' cognitive problems makes it interesting. It's good to see they are talking about needing to do a proper trial.

 

Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19”
Arman Fesharaki-Zadeh, et al

Highlights

• Combined treatment with the α2A-adrenoceptor agonist, guanfacine, and the anti-oxidant, N-acetylcysteine (NAC) reduced the cognitive deficits (“brain fog”) associated with long-COVID19 in eight out of twelve patients.

•Two patients stopped treatment due to hypotension and/or dizziness, common side effects of guanfacine, and two patients were lost to follow-up.

•The remaining eight patients reported improved working memory, concentration and executive function, including the resumption of normal workloads.

• One patient temporarily stopped guanfacine due to a hypotensive episode and reported a return of cognitive deficits that abated with resumed guanfacine treatment.

• Although placebo-controlled trials will be needed to demonstrate efficacy, the established safety of guanfacine and NAC suggests they may be immediately useful in treating the cognitive deficits of long-COVID19.

Abstract

Background
Prolonged cognitive deficits (“brain fog”) following COVID19 infection (long-COVID) are common and debilitating, yet there are currently no approved treatments. Cognitive impairment particularly targets the working memory and executive functions of the prefrontal cortex (PFC). The PFC has unusual neurotransmission and neuromodulation that render it vulnerable to stressors, and basic research has identified mechanisms that protect PFC connections. Based on the basic neuroscience data, we tried a combined open label treatment to bolster prefrontal function: the α2A-adrenoceptor agonist, guanfacine, which strengthens prefrontal connectivity, and the anti-oxidant, N- acetylcysteine (NAC), which protects mitochondria and reduces kynurenic acid blockade of NMDA receptors.

Case report
Twelve patients with “brain fog” including difficulties in executive functions were treated with guanfacine (1mg, PO bedtime for the first month, increased to 2mg after 1 month, if well-tolerated) and 600 mg NAC daily. Guanfacine+NAC improved cognitive abilities in eight of the twelve patients; four patients discontinued therapy, two for unspecified reasons and two due to hypotension and/or dizziness, common side effects of guanfacine. Those who stayed on guanfacine+NAC reported improved working memory, concentration, and executive functions, including a resumption of normal workloads. One patient briefly stopped taking guanfacine due to a hypotensive episode and reported a return of cognitive deficits that abated with resumed guanfacine treatment.

Conclusion
Although placebo-controlled trials will be needed to more rigorously demonstrate efficacy, as these agents have established safety, they may be immediately helpful in treating the large number of patients suffering from prolonged cognitive deficits following COVID19 infection.