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DOI: 10.1055/s-2005-918650
Effects of lithium on the HPA axis in patients with unipolar major depression
Objective (I) The combined dexamethasone/CRH test (DEX/CRH test) shows an overstimulation of ACTH and cortisol in depressed patients. Under tricyclic antidepressants, a normalization of the HPA axis overdrive was found to precede the clinical improvement. (II) Lithium is a well established drug for the treatment of affective disorders. Yet, its exact mode of action and its effects on the HPA axis are still unknown.
Design and Methods Three 4-week studies with each 30 acutely depressed patients (unipolar, SCID I confirmed) were conducted. In study 1, patients refractory to a treatment trial with an antidepressant of at least four weeks were treated with lithium augmentation. In study 2 and 3, drug free patients were treated with lithium monotherapy or citalopram monotherapy respectively. Weekly HAM-D ratings were performed. In each study, the DEX/CRH test was conducted right before and four weeks after initiation of the pharmacotherapy.
Results All 3 pharmacological strategies showed good antidepressive efficacy. Both lithium monotherapy and lithium augmentation led to a increase in the HPA axis activity. In contrast, citalopram therapy resulted in a decrease of the hormone response to the DEX/CRH test.
Conclusion Lithium has HPA axis activating effects in depressed subjects. This is in line with results of former laboratory and animal studies. A down-regulation of the HPA axis does not seem to be a necessary prerequisite of an effective antidepressive drug response.