Prospective trial of efficacy and safety of ondansetron and fluoxetine in patients with obstructive sleep apnea syndrome.
Author(s): Prasad B, Radulovacki M, Olopade C, Herdegen JJ, Logan T, Carley DW
Affiliation(s): Center for Narcolepsy, Sleep and Health Research, Department of Medicine, University of Illinois at Chicago, 845 South Damen Ave, Chicago, IL 60612, USA.
Publication date & source: 2010-07-01, Sleep., 33(7):982-9.
Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't
STUDY OBJECTIVE: Incremental withdrawal of serotonin during wake to sleep transition is postulated as a key mechanism that renders the pharyngeal airway collapsible. While serotonin promotion with reuptake inhibitors have demonstrated modest beneficial effects during NREM sleep on obstructive sleep apnea (OSA), animal studies suggest a potential therapeutic role for selective serotonin receptor antagonists (5-HT3) in REM sleep. We aimed to test the hypothesis that a combination of ondansetron (Ond) and fluoxetine (Fl) may effectively reduce expression of disordered breathing during REM and NREM sleep in patients with OSA. DESIGN AND SETTING: A prospective, parallel-groups, single-center trial in patients with OSA. PARTICIPANTS: 35 adults with apnea hypopnea index (AHI) > 10; range 10-98. INTERVENTION: Subjects were randomized to placebo, n = 7; Ond (24 mg QD), n = 9; Fl (5 mg QD) + Ond (12 mg QD), n = 9; and Fl (10 mg QD) + Ond (24 mg QD), n = 10. MEASUREMENTS AND RESULTS: AHI was measured by in-lab polysomnography after a 7-day no-treatment period (Baseline) and on days 14 and 28 of treatment. The primary endpoint was AHI reduction at days 14 and 28. OND+FL resulted in approximately 40% reduction of baseline AHI at days 14 and 28 (unadjusted P < 0.03 for each) and improved oximetry trends. This treatment-associated relative reduction in AHI was also observed in REM and supine sleep. CONCLUSIONS: Combined treatment with OND+FL is well-tolerated and reduces AHI, yielding a potentially therapeutic response in some subjects with OSA.