Trazodone improves obstructive sleep apnea after ischemic stroke: a randomized, double-blind, placebo-controlled, crossover pilot study

Background: Low arousal threshold plays a part in the pathogenesis of obstructive sleep apnea (OSA) and may be improved by sedatives. Sedative antidepressants are frequently prescribed for stroke patients due to their high prevalence of insomnia and depression. However, the effect of sedative antidepressants on the severity of OSA in stroke patients has not been studied well. Methods: In a double-blinded randomized crossover pilot study, 22 post-acute ischemic stroke patients (mean age, 61.7 ± 10.6 y) with OSA received 100 mg of trazodone or a placebo just before polysomnography, with approximately 1 week between measures. The study also measured baseline heart rate variability and 24-h ambulatory blood pressure. Results: Administration of trazodone significantly increased the percentage time of slow-wave sleep (31.5 ± 13.2 vs. 18.4 ± 8.7%; P < 0.001) and improved almost all the parameters of OSA severity, including the apnea–hypopnea index (AHI, 25.4 ± 15.4 vs. 39.1 ± 18.4 events/h; P < 0.001), the respiratory arousal index (9.8 (5.8–11.95) vs. 14.1 (11.3–18.7) events/h; P < 0.001), and the minimum oxygen saturation (80.2 ± 9.1 vs. 77.1 ± 9.6%; P = 0.016). Responders to therapy (AHI reduced by > 50%; n = 7/22) had predominant OSA during rapid-eye-movement sleep and decreased sympathetic tone, as reflected in significantly lower mean blood pressure, diastolic blood pressure, and normalized low-frequency power. Conclusions: Obstructive sleep apnea with comorbid ischemic stroke may be a distinctive phenotype which responds quite well to trazodone, decreasing OSA severity without increasing nocturnal hypoxia. Trial Registration: Clinicaltrials.gov: NCT04162743, 2019/11/10.