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

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. Nonresponse 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.