Institute of Neuroscience

Randomised controlled trial of antiglucocorticoid.

The ADD Study: Randomised controlled trial of antiglucocorticoid augmentation (metyrapone) of anti-depressants in depression

Many depressed patients respond poorly to anti-depressants and have treatment refractory depression (TRD). Many depressed patients have dysfunction of the HPA axis and we have shown that this is associated with reduced responses to anti-depressants. 

Pilot studies have shown that adding an antiglucocorticoid to anti-depressants may produce effects in TRD as did a study of the cortisol synthesis inhibitor metyrapone.  With EME funding we carried out a multi-centre RCT of metyrapone in 165 patients with moderate to severe TRD. 

Metyrapone was ineffective even in patients with abnormal HPA which suggests that simple reduction of cortisol is not associated with clinical improvement in depression and indicates that other measures targeting the HPA axis should be studied. 

We examined biological measures and found a number of important abnormalities in TRD.  However, metyrapone was not associated with differing outcomes on these measures.

Newcastle University staff and students linked to the project:

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