Corticosteroids with low glucocorticoid activity as a potential therapeutic strategy for post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome in patients with bipolar affective disorder: A case report. — CFSMEATLAS
Corticosteroids with low glucocorticoid activity as a potential therapeutic strategy for post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome in patients with bipolar affective disorder: A case report.
Nakajima, Kan, Ayani, Nobutaka, Matsuoka, Teruyuki et al. · PCN reports : psychiatry and clinical neurosciences · 2025 · DOI
Quick Summary
This case report describes one patient with bipolar disorder who developed ME/CFS after COVID-19 and was treated with different types of steroid medications. Strong steroids (betamethasone and prednisolone) triggered a severe manic episode requiring hospitalization, but a weaker steroid (hydrocortisone) improved her fatigue without worsening her mood. The findings suggest that choosing the right type of steroid may be important for ME/CFS patients who also have mood disorders.
Why It Matters
This case highlights that ME/CFS patients with existing psychiatric conditions require individualized corticosteroid treatment strategies. The observation that different steroid types have markedly different psychiatric effects suggests that receptor selectivity should guide therapeutic choice, potentially improving outcomes and safety in this vulnerable population.
Observed Findings
High-potency glucocorticoid receptor-dominant steroids (betamethasone and prednisolone) triggered acute mania with psychotic features in a patient with bipolar disorder.
Steroid withdrawal led to metabolic alkalosis and hypoxemia secondary to hypothalamic hypoadrenalism.
Physiological hydrocortisone replacement resolved fatigue and physical symptoms without destabilizing psychiatric status.
Hydrocortisone, which has relatively higher mineralocorticoid receptor activity and lower glucocorticoid receptor potency, was tolerated without mood episode recurrence.
Inferred Conclusions
Glucocorticoid receptor-dominant corticosteroids may exacerbate psychiatric instability in patients with mood disorders.
Mineralocorticoid receptor-favoring agents such as hydrocortisone may offer a safer alternative for managing HPA axis dysfunction in ME/CFS patients with comorbid psychiatric conditions.
Corticosteroid therapy in patients with both ME/CFS and mood disorders should be individualized based on receptor selectivity and integrated endocrinological-neuropsychiatric assessment.
Receptor selectivity plays a critical role in determining both efficacy and tolerability of corticosteroid therapy.
Remaining Questions
Would hydrocortisone show safety and efficacy benefits over other corticosteroids in a larger controlled trial of ME/CFS patients with mood disorders?
What This Study Does Not Prove
This is a single case report and cannot establish causation or define prevalence—it does not prove that all ME/CFS patients with bipolar disorder will respond similarly to these medications. The findings cannot be generalized beyond this patient, and controlled trials are needed to test whether hydrocortisone is broadly superior to other steroids in this subgroup.
Tags
Symptom:Fatigue
Phenotype:Infection-TriggeredLong COVID Overlap
Method Flag:PEM Not DefinedNo ControlsSmall SampleExploratory Only