Prednisolone suppression test in depression: prospective study of the role of HPA axis dysfunction in treatment resistance

Mario F Juruena, Carmine M Pariante, Andrew S Papadopoulos, Lucia Poon, Stafford Lightman, Anthony J Cleare

Research output: Contribution to journalArticle (Academic Journal)peer-review

91 Citations (Scopus)


BACKGROUND: People with severe depressive illness have raised levels of cortisol and reduced glucocorticoid receptor function.

AIMS: To obtain a physiological assessment of hypothalamic-pituitary-adrenal (HPA) axis feedback status in an in-patient sample with depression and to relate this to prospectively determined severe treatment resistance.

METHOD: The prednisolone suppression test was administered to 45 in-patients with depression assessed as resistant to two or more antidepressants and to 46 controls, prior to intensive multimodal in-patient treatment.

RESULTS: The patient group had higher cortisol levels than controls, although the percentage suppression of cortisol output after prednisolone in comparison with placebo did not differ. Non-response to in-patient treatment was predicted by a more dysfunctional HPA axis (higher cortisol levels post-prednisolone and lower percentage suppression).

CONCLUSIONS: In patients with severe depression, HPA axis activity is reset at a higher level, although feedback remains intact. However, prospectively determined severe treatment resistance is associated with an impaired feedback response to combined glucocorticoid and mineralocorticoid receptor activation by prednisolone.

Original languageEnglish
Pages (from-to)342-9
Number of pages8
JournalBritish Journal of Psychiatry
Issue number4
Publication statusPublished - Apr 2009


  • Adolescent
  • Antidepressive Agents/therapeutic use
  • Case-Control Studies
  • Depressive Disorder/drug therapy
  • Drug Resistance/drug effects
  • England
  • Female
  • Glucocorticoids
  • Humans
  • Hydrocortisone/metabolism
  • Hypothalamo-Hypophyseal System/drug effects
  • Male
  • Pituitary-Adrenal System/drug effects
  • Prednisolone
  • Prospective Studies
  • Receptors, Glucocorticoid/metabolism
  • Severity of Illness Index
  • Treatment Outcome


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