Chronobiologic parameter changes in patients with major depressive disorder and sleep disturbance treated with adjunctive brexpiprazole: An open-label, flexible-dose, exploratory substudy.

Abstract

BACKGROUND:

Circadian rhythm disturbances have been reported in patients with major depressive disorder (MDD). Among these is an increased phase angle between peak cortisol concentration and dim-light melatonin onset (DLMO). The aim of this study was to evaluate changes in chronobiologic parameters of sleep in patients with MDD receiving adjunctive brexpiprazole.

METHODS:

This was an interventional, multicenter, open-label, flexible-dose, exploratory study in patients with MDD and inadequate response to antidepressant treatment who were experiencing sleep disturbances. Patients received adjunctive brexpiprazole 2-3 mg/day for 8 weeks. Outcome measures included cortisol and melatonin levels, used to calculate phase angle, and the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN).

RESULTS:

The mean (standard error) phase angle between peak cortisol and DLMO increased by 108 (61) minutes from baseline to Week 8 (n = 9). BRIAN Total score changed (improved) by -14.6 (4.6) points from baseline to Week 8 (n = 9). Change in phase angle and BRIAN Total score showed a moderate-to-high correlation (Pearson coefficient: 0.68; 95% confidence limits: 0.04, 0.93; p = 0.040).

LIMITATIONS:

This study is limited by its small sample size, and its single-arm, open-label design.

CONCLUSIONS:

The findings provide a preliminary indication that the phase angle between peak cortisol and DLMO is of interest as a potential biomarker for depression and therapeutic response. Adjunctive brexpiprazole may represent a strategy for correcting circadian dysfunction in patients with MDD and inadequate response to antidepressant treatment. ClinicalTrials.gov identifier: NCT01942733.

• Authors: Andrew D Krystal, Aurélia Mittoux, Annika Lindsten, Ross A Baker
• Journal: Journal of affective disorders (J Affect Disord) Vol. 278 Pg. 288-295 (01 01 2021) ISSN: 1573-2517 [Electronic] Netherlands
• PMID: 32979560 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Quinolones
• Thiophenes
• brexpiprazole
• Melatonin

Topics

• Circadian Rhythm
• Depressive Disorder, Major (drug therapy)
• Drug Therapy, Combination
• Humans
• Melatonin (therapeutic use)
• Quinolones
• Sleep
• Thiophenes
• Treatment Outcome