Prospective trial of efficacy and safety of ondansetron and fluoxetine in patients with obstructive sleep apnea syndrome.
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.


METHODS
A prospective, parallel-groups, single-center trial in patients with OSA.


METHODS
35 adults with apnea hypopnea index (AHI) > 10; range 10-98.


METHODS
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.


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.
Prasad
Bharati
B
Center for Narcolepsy, Sleep and Health Research, Department of Medicine, University of Illinois at Chicago, 845 South Damen Ave, Chicago, IL 60612, USA.
Radulovacki
Miodrag
M
Olopade
Christopher
C
Herdegen
James J
JJ
Logan
Thomas
T
Carley
David W
DW
D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017294:Ondansetron / Q000009:adverse effects / Q000627:therapeutic use*; D017286:Polysomnography / Q000379:methods / Q000706:statistics & numerical data; D011446:Prospective Studies; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy*; D016896:Treatment Outcome
D005473:Fluoxetine; D017294:Ondansetron; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors