A combination of two existing medications for concussion and attention deficit hyperactivity disorder (ADHD) may help to alleviate brain fog in those suffering from long COVID. In a small-scale study, eight out of 12 patients experienced improvements in executive function, working memory, and concentration after being treated with the FDA-approved drugs.
Long COVID is a loosely defined condition characterized by persistent symptoms that linger for weeks, months, or even years after contracting the SARS-CoV-2 virus. Though different patients may experience different symptoms, many complain of unrelenting cognitive deficits, otherwise known as brain fog.
After noticing the similarities between COVID-related brain fog and general concussive symptoms, Dr Arman Fesharaki-Zadeh from the Yale School of Medicine decided to treat long COVID patients with a drug called N-acetylcysteine (NAC), which is generally prescribed for the treatment of traumatic brain injuries. Encouraged by positive outcomes, he then added an ADHD drug called guanfacine to the mix, and found that the combination of these medications helped to alleviate brain fog.
“There’s a paucity of treatment out there for long COVID brain fog, so when I kept seeing the benefits of this treatment in patients, I felt a sense of urgency to disseminate this information,” said Fesharaki-Zadeh in a statement. And while proper clinical trials involving this treatment regimen have yet to be conducted, the fact that both drugs are already approved by the FDA means that they are readily available and known to be safe.
“You don’t need to wait to be part of a research trial. You can ask your physician – these drugs are affordable and widely available,” explained Fesharaki-Zadeh.
Though not intended to treat COVID-19 symptoms, both NAC and guanfacine help to protect the prefrontal cortex (PFC) from stress. In their write-up, the study authors explain that brain fog is likely to arise from damage to neural connections within this key brain area.
More specifically, they say that inflammation triggers an overload of calcium in the PFC, leading to the destruction of synapses and producing serious cognitive deficits. Because NAC is an antioxidant, the researchers suspected that it may help to limit inflammation in the brain, while guanfacine causes potassium channels throughout the PFC to close, thereby strengthening neural connections.
“I had the idea of approaching the treatment from two different perspectives – modifying the pro-inflammatory, pro-oxidation pathway with NAC, and treating the post-COVID neurocognitive sequelae impacting executive functioning with guanfacine,” said Fesharaki-Zadeh.
The study authors tested their approach on 12 patients, two of whom dropped out of the study for unknown reasons while another two discontinued treatment after experiencing side effects such as low blood pressure and dry mouth. “The remaining eight patients reported improved working memory, concentration and executive function, including the resumption of normal workloads,” write the researchers.
The authors highlight the case of one particular participant who experienced significant improvements after initiating treatment but later stopped taking the medications after suffering spells of dizziness. When her symptoms returned, the patient resumed treatment and was once again relieved of her brain fog, this time with no dizziness.
“This was not a placebo-controlled trial, but anecdotes like this make one more confident that the relief is really due to the drug and not the placebo effect,” explained study author Dr Amy Arnsten.
The researchers are hopeful that their findings will inspire a major clinical trial into the use of NAC and guanfacine for long COVID, and encourage anyone suffering from brain fog to ask their doctor about the possibility of prescribing these two drugs.
“If patients have a physician who can read our paper, we’re hoping that they can access help right now,” said Arnsten.
The study is published in the journal Neuroimmunology Reports.