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Clinical Trial
. 2011;6(11):e27613.
doi: 10.1371/journal.pone.0027613. Epub 2011 Nov 23.

Lithium monotherapy increases ACTH and cortisol response in the DEX/CRH test in unipolar depressed subjects. A study with 30 treatment-naive patients

Tom Bschor  1 , Dirk Ritter, Patricia Winkelmann, Sebastian Erbe, Manfred Uhr, Marcus Ising, Ute Lewitzka
Affiliations
Clinical Trial

Lithium monotherapy increases ACTH and cortisol response in the DEX/CRH test in unipolar depressed subjects. A study with 30 treatment-naive patients

Tom Bschor et al. PLoS One. 2011.

Abstract

Background: Distorted activity of the hypothalamic-pituitary-adrenocortical (HPA) system is one of the most robustly documented biological abnormalities in major depression. Lithium is central to the treatment of affective disorders, but little is known about its effects on the HPA system of depressed subjects.

Objective: To assess the effects of lithium monotherapy on the HPA system of patients with major depression by means of the combined DEX/CRH test.

Method: Thirty drug-naive outpatients with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed) were treated with lithium monotherapy for four weeks. The DEX/CRH test was conducted directly before intake of the first lithium tablet and four weeks thereafter. Weekly ratings with the HDRS(21) were used to determine response (≥50% symptom reduction) and remission (HDRS ≤7).

Results: Lithium levels within the therapeutic range were achieved rapidly. Tolerability was good; no patient terminated the treatment prematurely. Response and remission rates were 50% and 33% respectively. Compared to the DEX/CRH test before the start of the treatment, a considerable and significant increase in all CRH-stimulated ACTH and cortisol parameters could be detected in the second DEX/CRH test. When analysed with particular regard to responders and non-responders, that significant increase was only present in the responders.

Conclusions: We were able to demonstrate that lithium leads to a significant activation of the HPA system. This is possibly connected to stimulation of hypothalamic arginine vasoporessin (AVP), to direct intracellular effects of lithium on pituitary cells and to an induction of gene expression.

Trial registration: drks-nue.uniklinik-freiburg.de DRKS00003185.

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Conflict of interest statement

Competing Interests: Over the past five years TB has received honoraria for speaking from Lilly, AstraZeneca, Esparma, Bristol-Myers Squibb, Sanofi-Aventis, Servier, and Lundbeck, and has accepted reimbursements of travelling expenses to congresses from AstraZeneca and Lilly. Over the past five years SE has accepted reimbursements of travelling expenses to congresses from AstraZeneca. Over the past five years MI has received grant support from the German Federal Ministry of Education and Research, and has been consultant to MSD Merck, Whitehouse Station, New Jersey, United States of America. UL has received honoraria for speaking from AstraZeneca and has accepted reimbursements of travelling expenses to congresses from AstraZeneca and Lundbeck. The authors DR, PW and MU – except for income received from their primary employer – have received no financial support or compensation from any individual or corporate entity over the past five years for research or professional service. The authors declare for all authors that there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. CONSORT 2010 Flow Diagram.
Figure 2
Figure 2. ACTH and cortisol response in the combined DEX/CRH test on the day before lithium monotherapy (blue line) and after four weeks of lithium treatment (pink line) in responders and non-responders (n = 29).
See this image and copyright information in PMC

References

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