Effects of Adjunctive Brexpiprazole on Chronobiologic Parameters in Patients With Major Depressive Disorder and Sleep Disturbances

December 15, 2017

 

This poster was presented at the 30th annual  Psych Congress, held Sept. 16-19, 2017, in New Orleans, Louisiana.

Background: Sleep disturbances are frequent in major depressive disorder (MDD). Circadian rhythm disturbances and changes in melatonin and cortisol patterns may contribute to sleep symptomatology; the increased phase angle between melatonin and cortisol has been suggested as a potential biomarker for MDD. Brexpiprazole is a serotonin-dopamine activity modulator that is a partial agonist at serotonin 5-HT1A and dopamine D2 receptors, and antagonist at serotonin 5-HT2A and noradrenaline alpha1B/2C receptors, all with similar potency. We evaluated the effects of adjunctive brexpiprazole on chronobiologic parameters of sleep in patients with MDD and inadequate response to antidepressant therapy (ADT) (NCT01942733).

Methods: Enrolled patients continued treatment with their current ADT for 2 weeks. Those who still had an inadequate response and experiencing sleep disturbances, received 8-week open-label treatment with their current ADT and adjunctive brexpiprazole (1-3 mg/day).

Results: At week 8, total scores on the Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN), assessing disturbances in circadian rhythms, demonstrated a mean improvement of -17 points from a baseline of 52 points (N=41). Time to melatonin onset (trough), peak cortisol levels, and the phase angle (difference in time between melatonin onset and cortisol peak) was calculated at baseline and week 8 for a subgroup of 9 patients. At week 8, the phase angle had decreased from 653 minutes (SD 106) to 545 minutes (SD 155).

Conclusion: The normalization of circadian rhythms (BRIAN) and melatonin trough/peak cortisol levels after 8-week treatment with adjunctive brexpiprazole may contribute to overall improvements in sleep and symptoms of depression.

Authors: 
Aurelia Mittoux, PhD; Peter Meisels, MSc; Ross Baker, PhD; Andrew Krystal, MD
Sponsoring Organization: 
H. Lundbeck A/S
Year: 
2017
Tracks: 
Neurology/Neuroscience
Mood Disorders