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Volume 07 No. 06
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Case Reports

Sodium Oxybate and Sleep Apnea: A Clinical Case

Sarah Hartley, B.M., B.Ch.; Maria-Antonia Quera-Salva, M.D.; Mourad Machou, M.D.
AP-HP Hôpital Raymond Poincaré, Sleep Unit, Physiology Department, Versailles-St Quentin en Yvelines University, France


Sodium oxybate (GHB, Xyrem, Jazz Pharmaceuticals) is used to treat cataplexy in patients with narcolepsy. We report the case of a middle aged, normo-ponderal narcoleptic woman without risk factors who developed reversible sleep apnea and objective sleepiness when treated by sodium oxybate, with an apnea-hypopnea index (AHI) of 19.7 on sodium oxybate and AHI 4.8 without treatment. Despite a subjective improvement in vigilance, mean sleep latency on MWT decreased from 21 minutes to 8 minutes on sodium oxybate.


Hartley S; Quera-Salva MA; Machou M. Sodium oxybate and sleep apnea: a clinical case. J Clin Sleep Med 2011;7(6):667-668.

Sodium oxybate (GHB, Xyrem, Jazz Pharmaceuticals) is used to treat cataplexy in patients with narcolepsy. It is a central nervous system depressant causing sedation and respiratory depression in overdose (> 50 mg/kg), leading to the concern that the drug may trigger or worsen sleep apnea.1 A recent study of the acute effects of sodium oxybate (9 g/night in 2 doses) in patients suffering from obstructive sleep apnea with AHIs from 10-40 did not find any increase in obstructive events, although there was an increase in central events, and 3 patients developed significant nocturnal oxygen desaturations.2 A 2-week study at 4.5 g/night in 2 doses was reassuring.3 However, recent clinical case reports described increased AHI in a 60-year-old woman with a BMI of 26, and development of severe sleep apnea (AHI 45) in a 58-year-old man with a BMI of 32.4 Improvement of sleep apnea has also been reported, possibly linked to increases in slow wave sleep.5


Mrs H, aged 39, of African origin, 1.75 m and 65kg (BMI 21.2 kg/m2) first presented symptoms of narcolepsy at the age of 16 years with excessive daytime sleepiness, cataplexy, and frequent hypnagogic hallucinations. Narcolepsy was diagnosed in 1999 following polysomnography and MSLT, with reduced mean sleep latency, 2 REM sleep onset episodes (SOREM), and HLA typing of DRB1*15 DQB1*0602. Initial treatment was with modafinil 200 mg and fluoxetine 20 mg (see Table 1 for results of polysomnograms, daytime sleepiness testing, and treatment from 2003–2010). Cataplexy persisted, as did sleepiness (Epworth Sleepiness score 13) despite treatment; and in 2004, fluoxetine 20 mg was discontinued and venlafaxine 37.2 mg was initiated. Mrs. H continued to work and drive.

Treatment, clinical data, and results of PSG and MWT 2003-2010

Date of PSGTreatmentBMIESSMicro-arousals/hStage 1&2 sleep % TSTSWS % TSTREM % TSTIndex of periodic leg movements/hAHIMean sleep latency MWT (min)
    2003modafinil 200 mg21.21328867723011.5
fluoxetine 20 mg
    2004modafinil 200 mg21.21627.77681611.30.623
venlafaxine 37.5 mg
    2005modafinil 200 mg21.21641.58710333Not reportedNot performed
venlafaxine 37.5 mg
    2007modafinil 200 mg21.21621.58191016018.5
clomipramine 10 mg
clonazepam 0.6 mg
    2009modafinil 200 mg20.916326962513.40.221
clomipramine 10 mg
clonazepam 0.6 mg
    April 2010modafinil 300 mg23.51543.3705252.119.78
sodium oxybate 4.5 g
levothyroxine 100 μg
    September 2010modafinil 300 mg22.51934.5651025164.8Not performed
clomipramine 10 mg
levothyroxine 100 μg

[i] BMI, body mass index; ESS, Epworth Sleepiness Scale; AHI, apnea-hypopnea index; MWT, maintenance of wakefulness test.

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Table 1

Treatment, clinical data, and results of PSG and MWT 2003-2010

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PSGs in May 2004 and January 2005 found periodic leg movements and sleep fragmentation, but sleep latency on the maintenance of wakefulness tests (MWT) was satisfactory. Ferritin was normal, and no secondary cause of the leg movements apart from antidepressant treatment was found. Modafinil was increased to 300 mg/day, and 0.3 mg clonazepam was added to control leg movements. Venlafaxine was replaced by clomipramine 10 mg in 2006, and a trial of a dopamine agonist in 2008 (ropinirole) was poorly tolerated.

In 2009 Mrs. H underwent a thyroidectomy and started on levothyroxine 100 μg/day; her BMI increased to 23.5 kg/m2. Because of increased cataplexy, antidepressant treatment was withdrawn and sodium oxybate started at a dose of 4.5 g/day in 2 divided doses. Mrs. H was able to stop her clonazepam and felt that her sleep and daytime vigilance improved, although the ESS was stable. PSG showed a marked improvement in leg movements but sleep remained fragmented with the development of non-desaturating central and obstructive hypopneas (AHI 19.7) triggering arousals, and a marked reduction in mean sleep latency on the MWT to 8 minutes. Treatment by sodium oxybate was stopped, and repeat PSG 5 months later found a return of leg movements and disappearance of sleep apnea (AHI 4.8).


Mrs H has narcolepsy with cataplexy complicated by periodic leg movements, which improved when antidepressants were replaced by sodium oxybate, with the development of reversible sleep apnea. Could our finding be due to error? All PSGs were read by the same physician using the same equipment (Medatec, Brussels). Apneas were scored according to the AASM alternative scoring system (with > 50% airflow reduction and > 3% oxygen desaturation or arousal). Identical hypopnea scoring criteria were used for all PSGs. Mrs. H is compliant with treatment, and accidental overdose of treatment was ruled out. Were there clinical signs which could have alerted us to a potential risk of sleep apnea? Weight gain prior to starting sodium oxybate was moderate, and at no point was the BMI abnormal. ENT examination was normal. Of concern was the development of impaired vigilance on MWT despite an improvement in subjective sleepiness.

Other cases of sleep apnea triggered by sodium oxybate have been reported but in older patients with elevated BMI.4 Our patient, who was young and slender, lacked signs which would have alerted us to a potential risk of sleep apnea. Monitoring by oximetry has been suggested every two years for non obese patients treated by sodium oxybate,6 but as Mrs. H did not present desaturations, her sleep apnea would not have been detected. Our case shows that reversible sleep apnea induced by sodium oxybate can occur even in patients considered at low risk, and prescribers should remain vigilant.


This was not an industry supported study. The authors have indicated no financial conflicts of interest.



Zvosec DL, Smith SW, Hall BJ, authors. Three deaths associated with use of Xyrem. Sleep Med. 2009;10:490–3. [PubMed]


George CF, Feldman N, Inhaber N, et al., authors. A safety trial of sodium oxybate in patients with obstructive sleep apnea: Acute effects on sleep-disordered breathing. Sleep Med. 2010;11:38–42. [PubMed]


George CF, Feldman N, Zheng Y, et al., authors. A 2-week, polysomnographic safety study of sodium oxybate in obstructive sleep apnea syndrome. Sleep Breath. 2010 1 18;Epub ahead of print.


Seeck-Hirschner M, Baier PC, von Freier A, Aldenhoff J, Goder R, authors. Increase in sleep-related breathing disturbances after treatment with sodium oxybate in patients with narcolepsy and mild obstructive sleep apnea syndrome: two case reports. Sleep Med. 2009;10:154–5. [PubMed]


Ortega-Albas JJ, Lopez-Bernabe R, Diaz JR, Serrano AL, authors. Sodium oxybate and breathing. Sleep Breath. 2010;14:259[PubMed]


Feldman NT, author. Clinical perspective: monitoring sodium oxybate-treated narcolepsy patients for the development of sleep-disordered breathing. Sleep Breath. 2010;14:77–9. [PubMed Central][PubMed]