The GABAergic mechanism of sodium oxybate was able to increase simple movements in non-rapid eye movement sleep.
Sodium oxybate (SO), a first-line treatment of type 1 narcolepsy (NT1), has the ability to improve nocturnal rapid eye movement (REM) sleep behavior disorder (RBD) and REM sleep without atonia (RSWA) in patients with NT1, according to a newly published study.1
The study evaluated 19 children and adolescents with NT1 (mean age, 12.5 [±2.7] years; mean disease duration, 3.4 [±1.6] years) who underwent 3 months of stable treatment with SO. RSWA, automatically computed by means of the validated REM sleep atonia index (RAI) was significantly improved (P <.05) in patients who received the drug compared to baseline.
Study author Giuseppe Plazzi, MD, director, Sleep Laboratory, Department of Neurological Sciences, University of Bologna, and colleagues noted that the treatment “remarkably” reduced complex movements during REM sleep. They wrote that the improvements on RBD and RSWA point to a direct role of the drug in modulating motor control.
"In our cohort, the significant increase of RAI implies that the decrease of motor episodes during REM sleep cannot be only ascribed to the reduction of the amount of REM sleep and the increase of deep sleep, but reflects a direct effect of SO in improving and stabilizing muscle atonia during REM sleep,” Antelmi et al concluded.
Compared to baseline, children who received the drug improved in clinical complaints, as well as showed a decrease of the Epworth Sleepiness Scale (ESS) score (14.4 [±9.01] vs 3.25 [±4.87]; t = 5.05; P <.0001).
The treatment also had an effect on the different distribution of sleep stages. Compared to baseline, there was a decrease of the percentage of non-REM (NREM) sleep stage 1 (14.2 [±9.01] vs 3.25 [±4.87]; t = 4.04; P <.0005) and of REM sleep (23.1 [±7] vs 13.1 [±6.45]; t = –6.50; P <.0001), and an increase of NREM sleep stage 3 (11.1 [±10.13] vs 53.9 [±17.96]; t = –5.34; P <.0001).
Patients within the study underwent neurological investigations and video-polysomnography (v-PSG) at baseline and after 3 months of stable treatment with SO. In order to properly rate RBD episodes, v-PSG was independently analyzed by 2 sleep experts. The v-PSG included at least 3 electroencephalography (EEG) channels (frontal, central, and occipital leads, referred to the contralateral mastoid), bilateral electrooculogram, submentalis and anterior tibialis electromyography, respiratory parameters, and electrocardiogram.
Antelmi and colleagues noted, “this study offers class IV evidence of the positive effect of SO on modulation of muscle atonia during REM sleep in NT1 children, because of the absence of a control group.”
The investigators also noted that future studies are needed to confirm the findings in adults with NT1 and in patients with idiopathic RBD (iRBD).
In 2002, the original formulation of SO was approved as a central nervous system (CNS) depressant, marketed as Xyrem, to treat symptoms of narcolepsy in adults. The drug was only available through a risk evaluation and mitigation strategy (REMS) program mandated by the FDA. Additionally, it was approved with a black box warning because of its ability to potentially cause depression, seizures, coma, or death, especially in combination with other CNS depressants.2
In January 2017, the FDA approved the first generic version of sodium oxybate oral solution, for the treatment of both cataplexy and excessive daytime sleepiness in narcolepsy in adult patients. The treatment’s label was also expanded in October 2018, to include an indication to treat cataplexy or excessive daytime sleepiness in patients with narcolepsy ages 7 and older.3