The combined dexamethasone/CRH Test (DEX/CRH test) and prediction of acute treatment response in major depression.

In this study the predictive value of the combined
dexamethasone/CRH test (DEX/CRH test) for acute antidepressant
response was investigated. In 114 depressed inpatients suffering
from unipolar or bipolar depression (sample 1) the DEX/CRH test was
performed at admission and shortly before discharge. During their
stay in the hospital patients received different antidepressant
treatment regimens. At admission, the rate of nonsuppression (basal
cortisol levels >75.3 nmol/l) was 24.6% and was not related to
the later therapeutic response. Moreover, 45 out of 114 (39.5%)
patients showed an enhancement of HPA axis function at discharge in
spite of clinical improvement. In a second sample, 40 depressed
patients were treated either with reboxetine or mirtazapine for 5
weeks. The DEX/CRH test was performed before, after 1 week, and
after 5 weeks of pharmacotherapy. Attenuation of HPA axis activity
after 1 week was associated with a more pronounced alleviation of
depressive symptoms after 5-week mirtazapine treatment, whereas
downregulation of HPA system activity after 5 weeks was related to
clinical response to reboxetine. However, early improvement of HPA
axis dysregulation was not necessarily followed by a beneficial
treatment outcome. Taken together, performance of a single DEX/CRH
test does not predict the therapeutic response. The best predictor
for response seems to be an early attenuation of HPA axis activity
within 1 or 2 weeks. However, early improvement of HPA system
dysfunction is not a sufficient condition for a favourable
response. Since a substantial part of depressive patients display a
persistence of HPA axis hyperactivity at discharge, downregulation
of HPA system function is not a necessary condition for acute
clinical improvement either. Our data underline the importance of
HPA axis dysregulation for treatment outcome in major depression,
although restoration of HPA system dysfunction seems to be neither
a necessary nor a sufficient determinant for acute treatment
response.