Epilepsy Drug Shows Promise in Reducing Obstructive Sleep Apnea Symptoms

Sulthiame, an epilepsy drug sold under the brand name Ospolot in Europe, appeared to reduce symptoms of obstructive sleep apnea (OSA) in a late-breaking clinical trial presented at the European Respiratory Society (ERS) Congress 2024.¹

Patients who took the carbonic anhydrase inhibitor experienced fewer breathing interruptions during sleep and improved oxygen levels. The apnea-hypopnea index (AHI3a), which tracks the frequency of respiratory pauses, decreased by 17.8% in those on the lowest dose (100 mg), 34.8% on the medium dose (200 mg), and 39.9% on the highest dose (300 mg). When using the AHI4 measure for when oxygen levels were more severely affected, the reduction in respiratory pauses was nearly 50%. Patients also reported feeling less daytime sleepiness while on the medication.

These findings are based on a double-blind, randomized, placebo-controlled trial presented at the ERS Congress by Jan Hedner, MD, PhD, professor of respiratory medicine at Sahlgrenska University Hospital and the University of Gothenburg in Sweden and lead author of the study.²

The trial included 298 patients with OSA who were being treated at 28 different centers across Spain, France, Belgium, Germany, and the Czech Republic. All patients had reported that they could not tolerate or refused to use continuous positive airway pressure (CPAP) machines or mouthpieces designed to keep their airways open. Sulthiame is instead taken as an oral tablet and works by stimulating the upper airway muscles.

“The standard treatment for obstructive sleep apnoea is sleeping with a machine that blows air through a face mask to keep the airways open,” Hedner explained. “Unfortunately, many people find these machines hard to use over the long term, so there is a need to find alternative treatments. We also a need better understanding of the underlying mechanisms in OSA to help clinicians give more personalised treatment.”

New findings offer hope for patients with OSA who cannot tolerate CPAP machines | Image credit: sbw19 – stock.adobe.com

Participants were divided into 4 groups, with 74 patients taking the lowest dose of 100 mg of sulthiame daily, 74 patients taking 200 mg daily, 75 taking 300 mg daily, and 75 taking a placebo pill. Patients underwent polysomnography—which records breathing patterns, blood oxygen levels, heart rhythm, eye movements, and brain and muscle activity during sleep—at the beginning of the trial and after 4 and 12 weeks of treatment.

Some adverse effects of the epilepsy drug included paresthesia or pins and needles, headache, fatigue, and nausea, but these symptoms were generally mild or moderate.

For Americans, it’s important to note that sulthiame is not approved in the US, though it has shown promise as an alternative treatment for sleep-disordered breathing. It could also potentially reduce the need for CPAP machines, as Hedner told The American Journal of Managed Care^® after presenting prior findings at the American Thoracic Society 2024 International Conference in May 2024.³

During the interview, Hedner emphasized that sulthiame improved sleep quality, reduced hypoxia, and addressed excessive daytime sleepiness, and suggested it could be part of a more personalized, pharmacological approach to treating sleep-disordered breathing. He also highlighted the growing interest in non-CPAP therapies, including nerve stimulation and muscle training, as part of an evolving treatment landscape.

“Although sulthiame is already available as a treatment for childhood epilepsy, we still need to carry out a phase III study to confirm the beneficial respiratory effects of this drug in a larger group of patients with OSA,” Hedner said regarding the newer findings.²

Individuals with OSA frequently experience loud snoring, interrupted breathing throughout the night, and may wake up multiple times. This not only leads to fatigue but also raises the risk of developing high blood pressure, stroke, heart disease, and type 2 diabetes. OSA is a widespread condition, though many individuals are unaware they have it.

“Many of us know that we snore or that our partner snores,” said Sophia Schiza, MD, PhD, head of the ERS assembly on sleep-disordered breathing and professor of respiratory and sleep medicine in the School of Medicine at the University of Crete, Greece, who was not involved in the study. “If snoring is accompanied by other symptoms, such as waking up often in the night, feeling fatigued and/or sleepy during the daytime, then it’s time to speak to a doctor. Because obstructive sleep apnoea increases the risk of serious health problems such as high blood pressure, heart and metabolic disease, it’s vital that we diagnose and treat the condition.”

While treatments for OSA exist, they are not effective for everyone, highlighting the need for more personalized diagnostic and therapeutic options. Schiza added that this study is among the first to demonstrate promising results that drug therapy, specifically sulthiame, could benefit certain patients with OSA. Further research is needed to evaluate the long-term effects and potential side effects of sulthiame and similar treatments, including their impact on reducing blood pressure and preventing cardiovascular disease in people with OSA.

References

1. Schwarz E, Testelmans D. Emerging insights in prognostic aspects and positive airway pressure treatment for obstructive sleep apnoea. ERS Congress 2024 webinar. Presented September 10, 2024. https://k4.ersnet.org/prod/v2/Front/Program/Session?e=549&session=17922
2. Hedner J, et al. A randomized, double-blind, placebo controlled, dose-finding trial of sulthiame in obstructive sleep apnea. Presented at: ERS Congress 2024; September 10, 2024; Vienna, Austria. https://k4.ersnet.org/prod/v2/Front/Program/Session?e=549&session=17922
3. Santoro C. Dr Jan Hedner explores benefit of sulthiame, new avenue in SDB treatment. AJMC^®. May 21, 2024. Accessed September 10, 2024. https://www.ajmc.com/view/dr-jan-hedner-explores-benefit-of-sulthiame-new-avenue-in-sdb-treatment