The effects of atomoxetine and trazodone combination on obstructive sleep apnea and sleep microstructure: A double-blind randomized clinical trial study

Study objectives: we aimed to compare the effects of atomoxetine and trazodone (A-T) in combination with placebo in patients with obstructive sleep apnea (OSA). Methods: This randomized, placebo-controlled, double-blind, crossover trial study was conducted in adults with OSA referred to a Sleep Clinic. Participants with eligibility criteria were recruited. Patients were studied on two separate nights with one-week intervals, once treated with trazodone (50 mg) and atomoxetine (80 mg) combination and then with a placebo and the following polysomnography tests. Results: A total of 18 patients with OSA completed the study protocol, 9(50%) were male, the mean age was 47.5 years (SD = 9.8) and the mean Body mass index of participants was 28.4 kg/m2 (SD = 3.4). Compared with the placebo, the A-T combination resulted in significant differences in AHI (28.3(A-T) vs. 42.7 (placebo), p = 0.025), duration of the REM stage (1.3%TST (A-T) vs. 13.1%TST (placebo), p = 0.001), and the number of REM cycles (0.8 (A-T) vs. 4.7 (placebo), p = 0.001), number of apneas (38.3 (A-T) vs. 79.3 (placebo), p = 0.011), number of obstructive apneas (37.2 (A-T) vs. 75.2 (placebo), p = 0.011), oxygen desaturation index (29.5 (A-T) vs. 42.3 (placebo), p = 0.022) and number of respiratory arousals (43.2 (A-T) vs. 68.5 (placebo), p = 0.048). This decrement effect did not change among those with a low-arousal phenotype of OSA. Conclusions: The A-T combination significantly improved respiratory events' indices compared with placebo in patients with OSA. This combination is recommended to be assessed in a large trial. It could be an alternative for those who do not adhere to the standard available treatments for OSA.