A safety trial of sodium oxybate in patients with obstructive sleep apnea: Acute effects on sleep-disordered breathing.
OBJECTIVE
Sodium oxybate (SXB) is an approved drug for the treatment of excessive daytime sleepiness (EDS) and cataplexy in narcolepsy. Obstructive sleep apnea syndrome (OSAS) is a condition that frequently co-occurs with narcolepsy. Given the known central nervous system (CNS) depressant effects of SXB, this study aimed to examine its effects on sleep-disordered breathing (SDB) and sleep architecture in patients with OSAS.


METHODS
Sixty patients with a history of mild to moderate OSAS (apnea-hypopnea index [AHI]>or=10 and <or=40, mean oxygen saturation [SaO(2)] >or=75%) received one of four treatments of the following: (1) 9g SXB, (2) 9g SXB/modafinil 200mg, (3) zolpidem 10mg, and (4) placebo (PBO) in a randomized, crossover design on four consecutive nights followed by overnight polysomnography.


RESULTS
Forty-two patients (70%) completed the study. The mean change from baseline in AHI and mean SaO(2) was not significantly different among groups following treatment. Central apneas in patients treated with SXB increased, and clinically significant oxygen desaturations were seen in three patients with SXB treatment. The most common treatment related adverse events were headache and nausea.


CONCLUSIONS
These results suggest that nighttime administration of 9g SXB in patients with mild to moderate OSAS does not negatively impact SDB, as measured by mean change from baseline in AHI and SaO(2), but might increase central apneas and cause oxygen desaturation in some individuals and should be used with caution.
George
Charles F P
CF
University of Western Ontario, London Health Sciences Centre, 375 South Street, London, Ont., Canada N6A 4G5. Charles.George@LHSC.ON.CA
Feldman
Neil
N
Inhaber
Neil
N
Steininger
Teresa L
TL
Grzeschik
Susanna M
SM
Lai
Chinglin
C
Zheng
Yanping
Y
D000759:Adjuvants, Anesthesia / Q000009:adverse effects* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000627:therapeutic use; D015897:Comorbidity; D045422:Continuous Positive Airway Pressure; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009290:Narcolepsy / Q000188:drug therapy / Q000453:epidemiology; D010100:Oxygen / Q000097:blood; D017286:Polysomnography / Q000187:drug effects*; D011358:Product Surveillance, Postmarketing; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy* / Q000453:epidemiology; D012894:Sleep Stages / Q000187:drug effects; D012978:Sodium Oxybate / Q000009:adverse effects* / Q000627:therapeutic use; D000077334:Zolpidem
D000759:Adjuvants, Anesthesia; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D006993:Hypnotics and Sedatives; D011725:Pyridines; D012978:Sodium Oxybate; D000077334:Zolpidem; D000077408:Modafinil; D010100:Oxygen