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

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.

A viewpoint on aldosterone andBMIrelated brain morphology in relation to treatment outcome in patients with major depression

“…This molecular mechanism may contribute to the increase in vulnerability with respect to developing anxiety and depression‐like behavior. In accordance with this, a recent pilot study 91 has suggested that administration of the aldosterone release reducing 92,93 and TLR4 inhibiting compound glycyrrhizin (from an extract of glycyrrhiza glabra) improves outcome in hospitalized patients with major depression.…”

Treatment with Glycyrrhiza glabra Extract Induces Anxiolytic Effects Associated with Reduced Salt Preference and Changes in Barrier Protein Gene Expression

“…In the present study, the treatment with Glycyrrhiza glabra extract substantially reduced anxiety behavior in the elevated plus-maze test irrespective of the stressor exposure and may indicate specificity for this depression subtype. Anxiolytic and antidepressant effects of Glycyrrhiza glabra extract were already observed in animal [ 59 , 60 , 61 , 62 ] and human [ 25 , 26 ] studies, encouraging future drug development.…”

“…Inhibition of 11β-HSD2 results in a reduction in RAAS activity and an increase in blood pressure in animal models [ 21 , 22 ] and humans [ 21 , 23 , 24 ]. Treatment with glycyrrhizin induced antidepressant effects in two small studies in depressed patients [ 25 , 26 ]. Glycyrrhizin also has direct anti-inflammatory properties by blocking toll-like receptor 4 (TLR4) [ 27 , 28 ] and consequently protects neuronal function, potentially by influencing BBB [ 29 , 30 , 31 ] and white matter integrity [ 32 ] via claudins and other markers of the BBB.…”

Therapeutic Effects of Glycyrrhiza Glabra Linn.

“…Harald Murck et.al, 2020 [47] Glycyrrhiza glabra (GG) extract containing 7-8% of glycyrrhizin was administered at a dose of 2×700mg daily adjunct to standard antidepressants in hospitalized patients with major depression.…”