Mirtazapine Reduces Susceptibility to Hypocapnic Central Sleep Apnea in Males with Sleep Disordered Breathing - A Pilot Study.

Abstract

Studies in those with spinal cord injury (SCI) have demonstrated that medications targeting serotonin receptors may decrease the susceptibility to central sleep-disordered breathing (SDB). We hypothesized that mirtazapine would decrease the propensity to develop hypocapnic central sleep apnea (CSA) during sleep. We performed a single-blind pilot study on a total of 10 men with SDB (seven with chronic SCI and three non-injured) aged 52.0±11.2 years. Participants were randomly assigned to either mirtazapine (15mg) or a placebo for at least one week followed by a seven-day washout period before crossing over to the other intervention. Study nights included polysomnography and induction of hypocapnic CSA using a non-invasive ventilation (NIV) protocol. The primary outcome was CO2 reserve, defined as the difference between eupneic and end of NIV PETCO2 preceding induced hypocapneic CSA. Secondary outcomes included controller gain (CG), other ventilatory parameters, and SDB severity. CG was defined as the ratio of change in minute ventilation (V̇e) between control and hypopnea to the change in CO2 during sleep. CO2 reserve was significantly widened on mirtazapine compared to placebo (-3.8±1.2 vs. -2.0±1.5mmHg; p=0.015). CG was significantly decreased on mirtazapine compared to placebo (2.2±0.7 vs. 3.5±1.9L/(mmHg*min); p=0.023). There were no significant differences for other ventilatory parameters assessed or SDB severity between mirtazapine and placebo trials. These findings suggest that the administration of mirtazapine can decrease the susceptibility to central apnea by reducing chemosensitivity and increasing CO2 reserve, however considering the lack of changes in AHI, further research is required to understand this finding s significance.