Mineralocorticoid receptor-related markers and outcome of major depression

Abstract

A close association between vegetative regulation and affect is common knowledge. Recently, the role of aldosterone and the activity of its receptor [mineralocorticoid receptor (MR)] in the clinical outcome for treatment with standard antidepressants has been shown including low systolic blood pressure and a low concentration of plasma sodium (Na), both of which appear to be related to therapy resistance to standard antidepressants. We carried out a retrospective analysis of a double-blind placebo-controlled trial of St John's wort extract LI160 in 247 outpatients with major depression. The study did not show a difference between the treatment groups; therefore, a pooled dataset of the 6-week completer population of the trial was analyzed. The focus was on the moderating effect of blood pressure and electrolytes on clinical outcome (relative change in Montgomery-Asberg Depression Rating Scale). Low Na/K ratio and high K at screening predicted worse outcome after 6 weeks as measures with the Montgomery-Asberg Depression Rating Scale (P<0.01). Systolic blood pressure at the same time point did not influence the treatment outcome. In conclusion, signs of reduced peripheral MR sensitivity, as reflected by a lower plasma Na/K ratio and/or higher K concentration, predict worse outcome. This is in line with our recent data as well as neuroendocrine findings. The data indicate that widely collected biomarkers, which are related to MR activity, may be useful to identify patients, who are at risk of nonresponse to antidepressant treatment.

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“…In detail, we have described previously that a high ratio of salivary aldosterone/cortisol and low blood pressure may indicate a risk for antidepressant treatment resistance, potentially based on a low peripheral MR activity (11). In an independent population, we found evidence that a low ratio of plasma Na + /K + is linked to worse treatment outcome (36). Some of these markers appear to be trait or resilience markers, as they are stable over the treatment interval (12).…”