The plasma dexamethasone variable in depression: test-retest studies and early biophase kinetics

A dexamethasone suppression test (DST) was performed in 45 patients during depressive illness and after recovery. Thirty-one samples from patients in whom plasma cortisol was resistant to the suppressive action of dexamethasone contained significantly lower mean (+/- SD) concentrations of the test drug (0.63 +/- 0.39 ng/ml vs 1.10 +/- 0.53 ng/ml) during illness than after recovery and normalization of the DST. In a control group of 14 patients who exhibited adequate DST suppression during the depressive state and after recovery, the dexamethasone concentrations were unchanged (1.54 +/- 0.91 ng/ml vs. 1.30 +/- 0.92 ng/ml). To investigate further the influence of bioavailability or pharmacokinetics of the test drug on DST results, we conducted a catheter study during sleep in 11 endogenously depressed patients who received an oral 1.5 mg dose of dexamethasone at 11 p.m. The half-life of dexamethasone was markedly lower in five DST nonsuppressors (t1/2 = 160 +/- 33 minutes) than in six DST suppressors (t1/2 = 422 +/- 172 minutes). These preliminary results indicate that metabolism of dexamethasone should be controlled in studies evaluating the clinical utility of the DST.