The application of serial neuroendocrine challenge studies in the management of depressive disorder

This paper describes the use of serial neuroendocrine challenge studies in the assessment of depressive disorder, specifically the dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) stimulation test. The combined use of these challenge tests revealed high sensitivity (67%) and high predictive value for the identification of endogenous depression in contrast to schizophrenia (p less than 0.025) or nondepressed patients (p less than 0.005). Further, normalization or persistence of dysregulation of these tests was correlated with clinical outcome at 6 months. Normalization of the DST occurred in 26 of 32 patients (82%) and was significantly correlated with the timing of symptomatic improvement (p less than 0.01). Five of six patients (84%) who never normalized the DST suffered an early relapse in contrast to 4 of 26 patients who did normalize (p less than 0.005). Unlike the DST, normalization of the blunted thyrotropin (TSH) response to TRH injection was not significantly correlated with the timing of symptomatic improvement. Only 8 of 19 patients (42%) ever normalized the TSH response. However, none of these 8 normalized patients suffered relapse within 6 months in contrast to 7 of 11 patients (64%) who did not normalize (p less than 0.025). Thus, failure of normalization of either the DST or TRH test was associated with a group of patients at high risk for early relapse. In this study, the use of prophylactic antidepressant medications did not avert relapse in 9 of 11 relapsed patients who had persistent neuroendocrine dysregulation.