Steroid-Induced Psychosis Among COVID-19 Recovered Patients—Need for Attention

Abstract

The COVID-19 pandemic, caused by SARS-CoV-2, has been extensively studied for both respiratory and extrapulmonary manifestations, including neuropsychiatric ones, which are a significant cause for concern. Although the direct effects of SARS-CoV-2 on psychiatric health have been extensively studied, the negative effects of medications on mental health are often underreported. There are concerns about the unrestricted use of steroids during COVID-19, as some studies have suggested that it may lead to psychological disturbances, cognitive impairment, and behavioural changes.1 Patients who have been treated with steroids may present with long-term symptoms such as fatigue, depression, anxiety, stress, and loneliness, which can impair their daily life. These symptoms may be related to the sustained production of cytokines, reactive oxygen species, and immune dysregulation, which can increase the risk of further inflammation.1 Patients with acute COVID-19 infection and postCOVID-19 syndrome are highly sensitive to steroid-induced psychosis due to the continued effects of the virus on brain tissues and hypoxic injury.2 According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), steroidinduced psychosis is classified as a form of substance or medication-induced psychotic disorder.3 To diagnose this disorder, the patient must exhibit symptoms of mania, impaired cognition, abnormal psychomotor behavior, and disorganized speech, as well as at least one symptom of delirium or hallucinations. Thus, a thorough history, physical examination, laboratory findings, and the presence of characteristic features such as delusions or hallucinations can aid in the diagnosis of this disorder.3 Steroid-induced psychosis can manifest as early as 1 to 2 weeks after starting treatment or even after discontinuing the drug. Higher doses of dexamethasone and prednisolone have been associated with an increased risk of psychosis. In a metaanalysis of psychiatric and neuropsychiatric presentations associated with various coronavirus infections, including COVID-19, a total of 25 studies were examined. One of these studies, conducted in Hong Kong, found that 13 out of 1744 COVID-19 patients suffered from steroid-induced psychosis.4 The pathophysiology of steroid-induced psychosis is related to an extreme imbalance between glucocorticoid receptors and mineralocorticoid receptors. The hypothalamicpituitary-adrenal axis is disrupted, resulting in distorted cortisol levels due to the activation of pituitary glucocorticoid receptors by exogenous steroids while depleting endogenous cortisol levels.5 Medication-induced psychosis is dosedependent, as evidenced during the COVID-19 pandemic, where the treatment protocol involved short-term, high-dose steroid therapy, which led to psychotic manifestations as a side effect unrestrained drug usage.5 Although rare, psychosis can occur in acute cases of COVID-19 and post-COVID-19 syndrome, highlighting the importance of understanding the adverse effects of inappropriate steroid dosage and the impact of these drugs administered through different routes. It is essential to raise awareness among physicians and patients about the potential severity of psychosis with respective routes of administration. Multicentric global studies are needed to better understand steroid-induced psychosis in COVID-19 patients and to promote judicious use of steroids.