Sultiame Once Daily Cuts Sleep Apnoea Events by Up to 35 Percent, Lancet Study Finds
Germany: A new multicentre phase 2 clinical trial published in The Lancet has reported encouraging results for sultiame—a long-used anticonvulsant—as a potential once-daily treatment option for obstructive sleep apnoea (OSA).
Led by Prof Winfried Randerath from the University of Cologne and Bethanien Hospital, Solingen, Germany, the study found that the medication significantly reduced breathing disturbances and improved sleep-related symptoms over 15 weeks.
OSA affects a substantial portion of the global population, with roughly 15% of men and 7% of women living with the condition. Despite its prevalence, approved pharmacological treatments remain unavailable. Continuous positive airway pressure (CPAP) therapy is currently the gold standard, but long-term adherence is typically low, driving the search for alternative therapies. Sultiame, although widely used in Europe for epilepsy, has not been approved for OSA and is not FDA-approved in the United States.
To explore its potential benefit, researchers conducted the largest clinical trial to date evaluating sultiame for OSA. The trial included 298 adults across 28 hospitals and community centres in five European countries. Participants, aged 18–75 years with moderate to severe untreated OSA, were randomly assigned to receive placebo or sultiame in doses of 100 mg, 200 mg, or 300 mg. All participants took three visually identical tablets nightly within an hour of bedtime. Sleep assessments, including polysomnography, were carried out at baseline, week 4, and week 15.
The study’s primary endpoint focused on the relative change in the Apnea–Hypopnea Index (AHI3a)—a measure of breathing interruptions during sleep—between baseline and week 15. Secondary measures included absolute change in AHI, oxygen saturation levels, sleep fragmentation, and daytime sleepiness assessed through the Epworth Sleepiness Scale (ESS).
The key findings from the trial were as follows:
- Sultiame demonstrated a clear dose-dependent improvement in OSA outcomes.
- Compared with placebo, AHI3a decreased by 16.4% with the 100 mg dose, 30.2% with the 200 mg dose, and 34.6% with the 300 mg dose.
- Sleep fragmentation was reduced by 5.7 events per hour with the 200 mg dose and 6.7 events per hour with the 300 mg dose.
- Patients receiving 200 mg reported significant improvements in daytime sleepiness.
- No notable differences were observed across groups in quality-of-life scores or heart rate.
- Adverse events increased with rising doses: 73% in the 100 mg group, 84% in the 200 mg group, and 91% in the 300 mg group, versus 61% in the placebo group.
- Frequently reported side effects included paraesthesia, headache, nasopharyngitis, and COVID-19.
- Based on the balance between benefits and side effects, the 200 mg dose was considered the most favourable.
According to the study authors, the findings offer strong justification for advancing sultiame to further clinical development. With consistent improvements observed across breathing indices, nocturnal oxygenation, and sleep quality, the study provides a promising foundation for the first potential pharmacological treatment of OSA.
Reference:
Randerath W, Grote L, Stenlöf K, Fietze I, Chevts J, Buntinx E, Albares J, Kuhn K, Hansen C, Völp A, Hedner J; FLOW study investigators. Sultiame once per day in obstructive sleep apnoea (FLOW): a multicentre, randomised, double-blind, placebo-controlled, dose-finding, phase 2 trial. Lancet. 2025 Oct 25;406(10514):1983-1992. doi: 10.1016/S0140-6736(25)01196-1. Epub 2025 Oct 9. PMID: 41077049.
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