Adjunct Therapy With Glycyrrhiza Glabra Rapidly Improves Outcome in Depression-A Pilot Study to Support 11-Beta-Hydroxysteroid Dehydrogenase Type 2 Inhibition as a New Target

Harald Murck, Lisa Lehr, Johannes Hahn, Matthias C Braunisch, Daniela Jezova, Maxim Zavorotnyy, Harald Murck, Lisa Lehr, Johannes Hahn, Matthias C Braunisch, Daniela Jezova, Maxim Zavorotnyy

Abstract

Mineralocorticoid-receptor (MR) dysfunction as expressed by low systolic blood pressure and a high salivary aldosterone/cortisol ratio predicts less favorable antidepressant treatment outcome. Inhibition of peripheral 11-beta-hydroxysteroid-dehydrogenase type 2 (11betaHSD2) reverses these markers. We therefore tested the hypothesis that the 11betaHSD2 inhibitor glycyrrhizin affects treatment outcome via this mechanism. We administered Glycyrrhiza glabra (GG) extract containing 7-8 % of glycyrrhizin at a dose of 2 × 700 mg daily adjunct to standard antidepressants in hospitalized patients with major depression. These subjects were compared in an open-label fashion with patients, who did not receive GG (treatment as usual, TAU). Assessments were done at baseline and approximately 2 weeks after. Twelve subjects were treated with GG and compared to 55 subjects with TAU. At week 2, the Hamilton Depression Rating Scale (HAMD-21) change from baseline as well as the CGI-S change showed a significant time × treatment interaction (p < 0.03), indicating a possible therapeutic benefit of GG. Clinical benefit seems to be more pronounced in subjects with lower systolic blood pressure and significantly correlated with reduced sleep duration in the GG group. Our preliminary data show that treatment with the 11betaHSD2 inhibitor glycyrrhizin may possess a beneficial effect on antidepressant response, which may be specific to a defined depression subtype.

Keywords: aldosterone; cortisol; depression subtypes; inflammation; major depression; mineralocorticoid receptor; toll like receptor 4 (TLR4).

Conflict of interest statement

HM worked in the past for several pharmaceutical companies, including Acorda Therapeutics and Axovant. He is currently the owner of the consulting company Murck-Neuroscience LLC and holds a patent for the use of glycyrrhizin in the area of depression treatment. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2020 Murck, Lehr, Hahn, Braunisch, Jezova and Zavorotnyy.

Figures

Figure 1
Figure 1
Qualitative patterns for the biomarker-dependent differentiation of clinical outcome between GG-treated and not GG-treated (TAU) subjects. The treatment effect is determined by the ratio of the HAMD-21 at week 2 to that at baseline. A value of 1 refers to no change in HAMD-21; higher values to worsening; and lower values to improvement. Lower systolic blood pressure is related to lesser improvement in the TAU group, but larger improvement in the GG, which leads to a larger differentiation between the groups with lower systolic blood pressure. GG, Glycyrrhiza glabra add-on; TAU, treatment as usual.
Figure 2
Figure 2
GG-induced biomarker changes are correlated with clinical change. A clinically better outcome, as determined by the HAMD-21 ratio, is significantly correlated with a reduced total sleep time in the GG group. GG, Glycyrrhiza glabra add-on; TAU, treatment as usual.

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