Dexamethasone
Dexamethasone is a long-acting, extremely potent synthetic glucocorticoid — roughly 25-30 times the anti-inflammatory potency of cortisol — with essentially no mineralocorticoid activity. It is used for severe inflammation, cerebral oedema, chemotherapy nausea and (from COVID-19 trials) severe respiratory inflammation. Its long duration makes it strongly and durably HPA-suppressive, and it is markedly catabolic.
01 Overview
Dexamethasone's high potency and long biological half-life mean small milligram doses produce large, prolonged effects. It is the reference glucocorticoid for the dexamethasone suppression test and is used where sustained potent glucocorticoid action is needed. The RECOVERY trial established a mortality benefit in patients with severe COVID-19 requiring oxygen.
Because its effect lasts more than a day, dexamethasone suppresses the HPA axis strongly and cannot be dosed to mimic the natural cortisol rhythm. In physique terms it is aggressively catabolic and immunosuppressive, and WADA prohibits it in-competition by oral, IV, IM and rectal routes.
02 Mechanism
Highly potent, long-acting glucocorticoid receptor agonist; suppresses inflammatory transcription with negligible mineralocorticoid activity.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Anti-inflammatory | 0.75–9 mg/day | Oral | Wide range by indication; ~0.75 mg approximates 5 mg prednisone. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Very potent anti-inflammatory actionPowerful, durable suppression of inflammation and oedema. | ~25-30x cortisol | Clinical | |
| Reduced mortality in severe COVID-19RECOVERY trial demonstrated a survival benefit in oxygen-dependent patients. | ~one third fewer deaths on ventilation | Clinical | |
| Strong catabolismAggressive muscle protein breakdown and metabolic derangement with sustained use. | dose/duration dependent | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Prolonged HPA axis suppressionLong duration causes strong, durable adrenal suppression; withdrawal risk is high. | Severe | Universal with sustained use | Clinical | |
| Neuropsychiatric effectsInsomnia, agitation, mood elevation or, less often, depression and psychosis. | Moderate | Common at higher doses | Clinical | |
| ImmunosuppressionIncreased infection risk with its potent, sustained action. | Severe | Common | Clinical |