PTSD has been associated with HPA axis alterations, mainly consisting of reduced cortisol levels, elevated CRH and enhanced glucocorticoid receptor responsiveness. These findings led to the emergence of glucocorticoid-based therapeutic options for PTSD.

To outline the different glucocorticoid-based interventions for PTSD either for prophylactic or for curative treatment.

A systematic review was performed. The Medline database was searched using the following keywords: ‘PTSD’, ‘treatment’, ‘Glucocorticoids’, ‘hydrocortisone’.

Glucocorticoid-based therapeutic for PTSD comprise preventive and curative interventions. Preventive interventions mainly consist of administering one single bolus of hydrocortisone shortly following the exposure to a traumatic event. Evidence comes from six published trials, all positive. Curative interventions include: prescribing hydrocortisone over short periods of time to treat PTSD symptoms, using Glucocorticoids to augment psychotherapy (in particular exposure therapy) for PTSD and using Mifepristone, a glucocorticoid receptor antagonist. Moreover, novel glucocorticoid receptor modulators are currently being developed and tested on animal models as a potential curative treatment for PTSD.

Use of hydrocortisone in preventing PTSD might be tempting, as is the use of hydrocortisone or Glucocorticoid receptors antagonists/modulators in treating PTSD. Yet, it should be emphasized that these interventions are not mainstream yet. They rather reflect a revolutionary new direction.

The author has not supplied his/her declaration of competing interest.