President Trump is being treated for COVID-19 with dexamethasone, a potent steroid shown to reduce death risks and shorten recovery time.
The drug is typically reserved for severely ill patients because clinical trials suggest that people with milder COVID-19 might fare worse after getting it.
Drugs in its class of corticosteroids are 'well-known' to have psychiatric side effects.
Mood swings,confusion, aggression and agitation are categorized as 'more common' side effects of the drug.
However, they're considered a minimal risk when given in doses lower than 40mg per day.
It's not clear how much dexamethasone Trump is getting, but clinical trials using it to treat COVID-29 only dosed patients with 6mg per day.
President Donald Trump is being treated for COVID-19 with a steroid that is recommended for severe cases of the illness and that comes with risks of serious side effects, including mood swings, aggression and confusion.
Trump's medical team on Sunday said the president was started on dexamethasone, a generic steroid long and widely used to reduce inflammation associated with other diseases. The steroid was begun after Trump experienced low oxygen levels.
'The president is going to get a short course so I’m not worried about long-term effects of dexamethasone,' Dean of Brown University's School of Public Health, Dr Ashish Jha told Fox News.
'But we definitely see in 30-40 percent of people pretty substantial effects...[of] the anxiety, the agitation.'
Research has shown that just a few days on dexamethasone can leave patients with memory and cognitive deficits. Corticosteroids - the class of drugs dexamethasone belongs to - may cause psychiatric side effects in anywhere from 1.8 to 57 percent of patients taking them.
Experts' first worry was that the use of dexamethasone to treat Trump suggested he was very sick, since the $6 steroid may be dangerous to people with mild COVID-19.
But because it's been linked to everything from mania to memory problems, and aggression to psychosis, some are also concerned that the president's judgement could be impaired as he reportedly continues to work through his illness.
'Steroids are always very dangerous medications to use,' Dr Edward Jones-Lopez, an infectious disease specialist at the University of Southern California in Los Angeles told Reuters.
'That is why it [dexamethasone] is used in severe to critical patients...There can be neuropsychiatric side effects. These are medications that we use verdy, very carefully.'
White House officials have painted a rosy picture of Trump's condition, saying he could be discharged from the hospital as soon as Monday.
But dexamethasone has typically been reserved for more serious cases.
A study in June that was hailed as a breakthrough showed that use of the steroid reduced death rates by around a third among the most severely ill hospitalized COVID-19 patients.
Dexamethasone is used to treat immune system disorders, inflammatory conditions, breathing issues and other conditions by decreasing the body's natural defensive response, which can overreact causing additional problems.
The Infectious Disease Society of America says dexamethasone is beneficial to people with critical or severe COVID-19 who require extra oxygen. But studies show the drug may be harmful in people with milder COVID-19 because it can suppress their natural immune response.
In addition, side effects can include physical problems such as blurred vision and irregular heartbeat, as well as personality changes and difficulty thinking, according to the International Myeloma Foundation.
Dexamethasone is also a member of a group of long-acting glucocorticoids that comes with a particularly high risk of delirium, confusion or disorientation, as well as depression caused by withdrawal when treatment is over, compared to short-acting steroids.
The receptors that dexamethasone and other steroids target are not only key to combating dangerous inflammation, but play central roles in our memory cognition and the synaptic activity that keeps our thoughts flowing clearly and quickly.
A 2019 case report on a man who developed psychosis after an injection of dexamethasone to his scrotum, describes steroid-induced psychosis 'a well-documented phenomenon,' although an 'uncommon' one.
The report, from Baylor University Medical Center, also notes that research on the mental disturbances linked to dexamethasone or other steroids is sparse.
So there are not exact statistics for how many people treated with the steroid develop mood swings, aggression or any other psychiatric issues.
But these are considered 'more common' side effects of the drug and at least 79 instances were already recorded in 1985.
Most of those 79 people somewhat lost touch with reality, about 40 percent became depressive, 28 percent became manic and about 10 percent of people who had the bizarre reaction became delirious.
For most people, these strange mental disturbances appeared within less than two weeks after they received dexamethasone. They subsided within a few days for some, but lasted weeks for others (the most intense symptoms went away more quickly, while depression and mania lingered a bit longer).
The main risk factor for psychiatric effects is taking a high dose of steroids.
According to a Mayo Clinic study on steroids and psychiatric effect, the risk of having delirium, depression or other psychiatric side effects is 'minimal' so long as someone is getting 40mg or less a day.
White House physician Dr Sean Conley has not disclosed what dose of dexamethasone Trump got or is getting, but it was given to COVID-19 patients at a dose of just 6mg per day, so it's highly unlikely Trump's dose puts him in a high risk category.
However, dexamethasone is a common steroid used in many patients who have low oxygen as a result of COVID-19 and is typically harmless, said Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security.
President Trump has been given at least three potent drugs since announcing he tested positive for COVID-19 on Thursday night: Regeneron's cocktail of lab-made antibodies, the antiviral remdesivir, and the steroid dexamethasone.
Two of those medications are still experimental for treating COVID-19, and have given emergency use authorization by the Food and Drug Administration (FDA).
And White House physician Dr Sean Conley admitted on Monday that he would not disclose every single medication that the president is currently receiving (citing HIPAA patient privacy laws, which suggests that Trump himself gave Dr Conley permission to disclose some of his medications, but not all of them).
Remdesivir, dexamethasone and the antibody cocktail are all in ongoing trials - but it's unclear if anyone besides the US Commander-in-Chief has ever been treated with all three.
Those three drugs are 'as much as we know [about the president's treatment regimen] - but I found it all really confusing, based on the reports,' Dr Mark Poznansky, an infectious disease specialist at Massachusetts General Hospital told it.
When asked if there was any precedent for treating a COVID-19 patient with all three drugs, Dr Poznansky replied, 'no.'
'But the individual decisions are based on the individual patient, and all bets are off when you're dealing with the president, the commander-in chief,' he added.
'The implication is that the doctors believe that the risk of using these is outweighed by the potential benefit.'
And while we have some clarity on the potential side effects of each of the drugs, how they might interact is a mystery, 'because they just haven't been used frequently enough...we don't know about the combination,' Dr Poznansky said.
But even on their own, the side effects of these drugs could be particularly concerning for the president, considering that the steroid can cause mood swings, confusion and aggression.
The drugs he was treated with and their potential side effects are:
REGENERON'S EXPERIMENTAL ANTIBODY COCKTAIL DRUG
WHEN HE GOT IT: Trump received a single 8 gram dose of Regeneron's cocktail of lab-made antibodies on Friday.
WHAT IT DOES: REGN-COV2 is a combination of two lab-made versions of antibodies that help block the coronavirus from entering cells.
One of the antibodies in the 'cocktail' is based on an antibody that mice produce in response to coronavirus, while the other is based on an antibody isolated from the one of the first US COVID-19 patients.
The hope is that the treatment drives down viral load, keeping it from overrunning the body and sending the immune system haywire, and preventing the infection from becoming severe.
WHAT THE DATA SAYS: REGN-COV2 is still in early trial phases, but the first data from its clinical trial found that it dramatically lowered viral load within a week and cut recovery time in half in patients that weren't sick enough to be hospitalized.
Regeneron has not yet studied the drug in severely ill patients.
THE POSSIBLE SIDE EFFECTS: The main concern is these types of treatment occasionally trigger 'antibody-dependent enhancement,' which means the intended therapeutic actually helps the virus invade cells.
So far, the trials don't suggest that REGN-COV2 is causing this phenomenon.
Antibody treatments can also cause allergic reactions including anaphylaxis, as well as fever, chills, nausea, diarrhea, weakness, headache and low blood pressure.
REMDESIVIR, GILEAD'S ANTIVIRAL DRUG
WHEN HE GOT IT: President Trump was given his first dose of a five-day treatment course on Friday evening, after he was transferred from the White House to Walter Reed National Medical Center.
He has since received his second and third dose of the drug.
WHAT IT DOES: Remdesivir is an antiviral therapy originally designed to treat Ebola.
Scientists are not entirely sure why, but it helps to prevent coronavirus from making more copies of itself.
WHAT THE DATA SAYS: Late-stage clinical trials of remdesivir found that patients treated with the drug were more likely to recover within 11 days than those who did not get the drug.
Their survival odds were about 40 percent better. In May, the drug became the first to get emergency use authorization from the FDA for treating severely ill patients. That approval has since been expanded to any hospitalized patients.
THE POSSIBLE SIDE EFFECTS: It can cause nausea, vomiting, chils, sweating or light-headedness. The drug also may harm liver function, meaning that patients have to be closely monitored.
There was some suggestion the Trump's liver and kidney function were suboptimal last night, but Dr Conley said Monday the president was just 'dehydrated.'
DEXAMETHASONE, THE $6 STEROID WITH COMMON PSYCHIATRIC SIDE EFFECTS
WHEN HE GOT IT: The president got a dose of dexamethasone on Saturday after he developed a high fever and his blood oxygen levels dropped below 94 percent on two occasions.
WHAT IT DOES: Dexamethasone is a cheap steroid known to tamp down inflammation. It's already approved for use in other conditions in the US.
WHAT THE DATA SAYS: Although it hasn't yet been given emergency approval in the US, dexamethasone is the most promising treatment yet for coronavirus.
In a major UK study, the steroid cut the risk of death by 36 percent for patients sick enough to need breathing machines and by 18 percent for patients needing just supplemental oxygen.
However, it seemed harmful at earlier stages or milder cases of illness: 18 percent of those on the drug died versus 14 percent of those given usual care.
For that reason, many doctors were alarmed to see President Trump treated with the drug because using it suggested either that he was very sick, or that doctors were taking a risk in giving it to him early.
THE POSSIBLE SIDE EFFECTS: The steroid is potent, and can cause swelling, headaches, stomach pain, nausea, weakness, dizziness sleep problems, vision changes, skin problems, severe allergic reactions including mood changes.
These mood changes include aggression, agitation and confusion.
'Steroids are always very dangerous medications to use,' Dr Edward Jones-Lopez, an infectious disease specialist at the University of Southern California in Los Angeles, told Reuters.
'That is why it (dexamethasone) is used in severe to critical patients... There can be neuropsychiatric side effects. These are medications that we use very, very carefully.'