Reduced urine pregnenolone concentration after clinical response in patients with depression: An open-label short-term prospective study

Bruno Pedraz-Petrozzi; Eva Kathrin Lamadé; Rebekka Schneiberg; Barbara Scharnholz; Jana Vítků; Martin Hill; Ľuboslav Stárka; Maria Gilles; Michael Deuschle

doi:10.1016/j.psyneuen.2023.106366

Reduced urine pregnenolone concentration after clinical response in patients with depression: An open-label short-term prospective study

Psychoneuroendocrinology. 2023 Nov:157:106366. doi: 10.1016/j.psyneuen.2023.106366. Epub 2023 Aug 15.

Authors

Bruno Pedraz-Petrozzi¹, Eva Kathrin Lamadé², Rebekka Schneiberg², Barbara Scharnholz², Jana Vítků³, Martin Hill³, Ľuboslav Stárka³, Maria Gilles², Michael Deuschle²

Affiliations

¹ Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, J5, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany. Electronic address: Bruno.pedrazpetrozzi@zi-mannheim.de.
² Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, J5, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany.
³ Department of Steroids and Proteofactors, Institute of Endocrinology, Národni 8, 11694 Prague, Czech Republic.

PMID: 37597381
DOI: 10.1016/j.psyneuen.2023.106366

Abstract

Background: Identifying biological alterations in patients with depression, particularly those that differ between responders and non-responders, is of interest to clinical practice. Biomarker candidates involve neuroactive steroids, including pregnenolone (PREG) and allopregnanolone (ALLO). However, alterations in PREG and ALLO associated with treatment response are understudied. This study's main aim was to evaluate the effects of antidepressant treatment, clinical response, and treatment duration on PREG and ALLO in depression.

Materials and methods: In a 4-week, open-label trial, participants were allocated randomly to the venlafaxine (n = 27) or mirtazapine (n = 30) group. Urine concentrations of PREG and ALLO were assessed through gas chromatography-mass spectrometry. Participants collected night urine between 10:30 p.m. and 8:00 a.m. Two primary outcomes were analyzed. Firstly, the effect of treatment (mirtazapine or venlafaxine), clinical response (operationalized through the Hamilton Depression Rating Scale), and time (baseline compared to 28 days) on the urine concentrations of PREG or ALLO in depression. Finally, the effect of clinical response and time on the urine concentration of PREG or ALLO, independently of the antidepressant given (mirtazapine or venlafaxine). Linear mixed models were carried out.

Results: There was no significant difference in PREG and ALLO concentrations between baseline and 28 days in responders and non-responders when investigating the venlafaxine or the mirtazapine group. However, we found a significant reduction of urine PREG concentration after 28 days of treatment in responders who received either venlafaxine or mirtazapine (estimate = -0.56; p = 0.016; 95CI [-1.003; -0.115]; Cohen's d = -0.61).

Conclusions: Our main results indicate that responders in depression show reduced urinary PREG concentrations after 4-weeks of therapy, independently of the antidepressant used. More studies are needed to confirm these findings.

Keywords: Allopregnanolone; Biomarker; Depression; Neurosteroids; Pregnenolone; Treatment outcome.