A President on Steroids
Like many patients being treated for Covid-19, President Trump has been prescribed dexamethasone, a powerful steroid medication known to cause severe psychiatric symptoms in some patients. How severe can these symptoms get? How often do patients develop neuropsychiatric symptoms from steroids? Fortunately, many years of research allow for confident answers to these questions.
The term “steroid” is used to refer to a whole host of naturally occurring substances in the human body, as well as to synthetic molecules that mimic their effects that are used as pharmaceuticals. Dozens of four-ringed molecules classified as steroids carry out a variety of functions in the body, some are hormones, like the sex hormones testosterone and estrogen, and some are important components of cell membranes. Myelin, the fatty sheath that insulates the nerve fibers is largely composed of cholesterol, also a steroid.
In medical therapeutics, the term “steroid” usually refers to the subgroup of molecules called the “glucocorticoids.” As this name suggests, these substances are important regulators of glucose metabolism but they have many other functions as well. One of the most important of these is their role in the regulation of the immune system, specifically their anti-inflammatory effects. Millions of doses of 1% corticosterone cream are sold over-the-counter every year to treat the mild inflammation seen in poison ivy rashes and mosquito bites. More potent steroids such as cortisone and prednisone are prescribed for more serious inflammatory diseases such as asthma and rheumatoid arthritis. Dexamethasone, one of the most potent glucocorticoids, is reserved for the most severe conditions, its anti-inflammatory effect being 30 times stronger than that of corticosterone.
One of the first large-scale reports of the adverse psychiatric effects of steroids appeared in 1972. The Boston Collaborative Drug Surveillance Program evaluated 718 patients who had received prednisone, a drug with an anti-inflammatory potency that is only 4 times that of corticosterone. They reported that 21 (about 3%) of these patients developed psychiatric symptoms such as “inappropriate euphoria.” More recent studies, however, have demonstrated that psychiatric symptoms are many times more common than this. A 2007 study, in which patients were simply asked to report any reactions to steroid medications that they noticed, found that over half of them experienced changes in mood, with mood elevation and exaggerated feelings of well-being and vitality being the most commonly reported psychiatric reactions to steroid treatment.
The best description of the mood symptoms related to steroid medications can be found in a 1952 article from the American Journal of Psychiatry. In “The Psychological Response to ACTH, Cortisone, Hydrocortisone and Related Steroid Substances,” Drs. Howard Stone and Francis Braceland, two psychiatrists from the Mayo Clinic, described the symptoms in detail and even proposed a rating system for the severity of psychiatric reactions to steroid medications. Although early research articles in psychiatry like this one usually lack the careful numerical reporting and elaborate statistical analyses found in modern studies, what they lack in precision they more than make up for in detailed observation and vividness:
The authors reported for example that even mildly affected patients, which they rated as grade I, describe their mood changes “In a number of rather typical statements: 'I never felt better in my life!’; 'I’m on top of the world!’; 'I never realized what it was like to feel really well!’; 'For the first time in years I feel alive!' " The authors reported that “It has been our observation that mood is invariably changed in the direction of elevation” and that patients show “a liberal use of the superlative in their descriptions of their current health.”
In grade II reactions, there is an increase in these symptoms, with “patients [being] effusive and expansive in their affirmation of well-being. They are voluble and often given to hyperbole.” Sleeplessness was common at this stage as was an “accelerated mental activity” that “sometimes…approaches the hypomanic level,” the euphoric state characteristic of patients with bipolar disorder. The authors observe that frequently “The mood elevation is of a degree sufficient to impair judgment and perspective.”
In grades III and IV, patients developed increasingly severe psychiatric disturbances ranging from “constant crying, agitation and feeling of hopelessness” and “pronounced excitement” to “grossly psychotic reactions” including hallucinations and delusional thinking.
These observant clinicians noted “Approximately 60% of patients to whom [glucocorticoids] are given show responses in grades I or II,” a percentage strikingly similar to the 52% of patients who reported developing mood symptoms in the 2007 study. They also reported that many of the patients who developed grade III and IV symptoms had a prior history of psychiatric illness.
Although we do not know the dosage of dexamethasone that has been prescribed for the President, the recommended dose for Covid-19 patients is 6 mg daily for up to 10 days, which is steroid dosing comparable to what the patients in the studies referenced here were taking.
Given the substantial risk of significant psychiatric symptoms in patients taking dexamethasone, it is incumbent on the president’s physicians and those around him to observe him closely for the emergence of psychiatric symptoms. Just as important is that the appropriate persons have an action plan at the ready should symptoms become severe enough to impair the President’s judgment, which is, unfortunately, a real possibility.
The Boston Collaborative Drug Surveillance Program “Acute Adverse Reactions To Prednisone In Relation To Dosage,” Clinical Pharmacology and Therapeutics 13, no.5, Part 1 (1972) 694-698.
Fardet L., Flahault, A., et al, “Corticosteroid-Induced Clinical Adverse Events: Frequency, Risk Factors And Patient’s Opinion” British Journal of Dermatology 157 (2007) 142-148.
The RECOVERY Collaborative Group, “Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report” New England Journal of Medicine July 17, 2020
Rome, Howard and Francis Braceland, “The Psychological Response To ACTH, Cortisone, Hydrocortisone, And Related Steroid Substances” American Journal of Psychiatry 108, no. 9 (1952) 641-651.
Comments