For the approximately 30 million Americans living with obstructive sleep apnea, treatment has meant one thing for decades: a CPAP machine — a pressurized mask worn over the face during sleep, connected by a hose to a motorized pump that forces air through a collapsing airway throughout the night. The device works. The problem is that up to half of patients who need it stop using it within a year.
A European clinical trial published in The Lancet and featured by ScienceDaily in March 2026 offers the most promising evidence yet that the future of sleep apnea treatment may include a pill taken once before bed. The drug is sulthiame — an existing medication approved in several countries for childhood epilepsy — and in the highest doses studied, it reduced breathing interruptions during sleep by up to 47% and improved overnight oxygen levels compared to placebo.
"We have been working on this treatment strategy for a long time, and the results show that sleep apnea can indeed be influenced pharmacologically," said Jan Hedner, senior professor of pulmonary medicine at the Sahlgrenska Academy at the University of Gothenburg, who led the research.
What the Trial Found — Design, Participants, and Results
The FLOW trial — formally titled "Sulthiame once per day in obstructive sleep apnoea: a multicentre, randomised, double-blind, placebo-controlled, dose-finding, phase 2 trial" — enrolled 298 adults with moderate-to-severe obstructive sleep apnea across 28 centers in four European countries (the provided summary states five; multiple news reports confirm four). Participants were randomized to receive either placebo or sulthiame at one of several dosing levels. Neither participants nor researchers knew who received the active drug — a rigorous double-blind design.
The primary outcome was the apnea-hypopnea index (AHI) — the number of breathing interruptions per hour of sleep. The results:
- Patients receiving higher doses of sulthiame experienced up to 47% fewer breathing interruptions compared to placebo
- Overnight oxygen levels improved in the treatment group — a clinically important finding, as oxygen desaturation is the mechanism by which untreated sleep apnea damages the heart, brain, and kidneys over time
- Side effects were mostly mild and temporary , and the drug was generally well tolerated across the study population
The trial is classified as a Phase 2 dose-finding study — meaning its primary purpose was to determine the appropriate dose range for future Phase 3 efficacy confirmation. Sulthiame has not yet been approved for sleep apnea anywhere in the world. It is classified as an investigational drug for this indication in the United States and Canada.
| Sulthiame Sleep Apnea Trial Key Data | Detail |
| Published in | The Lancet (2025; 406 (10514): 1983) DOI: 10.1016/S0140-6736(25)01196-1 |
| ScienceDaily coverage | March 11, 2026 (University of Gothenburg source) |
| Trial design | Multicenter, randomized, double-blind, placebo-controlled, dose-finding, Phase 2 |
| Participants | 298 adults with moderate-to-severe OSA |
| Centers | 28 across European countries |
| Allocation | 1/4 placebo; remainder received different sulthiame doses |
| Key finding — high dose | Up to 47% fewer breathing interruptions vs. placebo |
| Key finding — oxygenation | Improved overnight oxygen levels in treatment group |
| Side effects | Mostly mild and temporary; drug well tolerated |
| Sulthiame mechanism | Stabilizes breathing control; increases respiratory drive; reduces upper airway collapse |
| Current approval status (sleep apnea) | Investigational — not approved for OSA in U.S. or Canada |
| Current approval status (epilepsy) | Approved in several countries for childhood epilepsy |
| Phase 3 trial status | Not yet initiated as of mid-2026 |
Why Sulthiame's Mechanism Makes It a Genuinely Different Kind of Treatment
To understand why this pharmacological approach is compelling, it helps to understand why OSA was long considered resistant to drug treatment. Obstructive sleep apnea occurs when the muscles of the upper airway — including the genioglossus tongue muscle and the pharyngeal dilators — relax during sleep to the point where the airway collapses. This collapse interrupts breathing and drops oxygen levels, which triggers the brain to partially arouse the sleeper to restore airway tone. The cycle can repeat hundreds of times per night.
Most drug approaches have tried to address this by targeting upper airway muscle tone directly — a pharmacologically difficult problem because the muscles involved are only one component of a multi-factor collapse process that also involves anatomy, airway pressure, and arousal threshold.
Sulthiame takes a different approach. The drug — a carbonic anhydrase inhibitor — works by affecting the brain's central control of breathing, increasing what is called "respiratory drive." By strengthening the brain's signal to breathe, sulthiame appears to reduce the likelihood that brief lapses in upper airway tone will result in complete airway collapse. According to the University of Gothenburg's press release: "Sulthiame works by stabilizing the body's breathing control and increasing respiratory drive, thereby reducing the risk of the upper airway collapsing during sleep."
This mechanism — central respiratory stabilization rather than peripheral muscle activation — represents a conceptually distinct pharmacological approach from most prior attempts to treat sleep apnea with medication.
The CPAP Problem — Why a Pill Matters So Much
CPAP (continuous positive airway pressure) therapy remains the gold standard for OSA treatment and is highly effective when used consistently. The problem is consistency. Multiple studies have documented that up to 50% of patients prescribed CPAP discontinue use within a year. Reasons cited include discomfort from the mask, noise, claustrophobia, difficulty with air pressure, dry mouth or nasal congestion, and the practical challenges of traveling with or maintaining the equipment.
For the millions of patients who cannot or will not tolerate CPAP — and the millions more who remain undiagnosed because they resist the prospect of CPAP — a well-tolerated oral medication that meaningfully reduces breathing interruptions and improves oxygen levels represents a transformative alternative. Even partial reduction in AHI can reduce the cardiovascular consequences of untreated sleep apnea, which include hypertension, heart failure, stroke, and type 2 diabetes.
Two FDA-approved alternatives to CPAP exist: oral appliances (mandibular advancement devices, worn in the mouth to keep the jaw and tongue forward) and surgical procedures. Neither is as broadly effective as CPAP, and neither approaches the simplicity of a once-daily pill. Daridorexant and other sleep medications treat insomnia, not sleep apnea. Tirzepatide (Zepbound) has shown efficacy in reducing sleep apnea severity in obese patients — but through weight loss as the mechanism, and only in that subgroup.
A pharmacological agent that works directly on the breathing control mechanism, applicable across body types and anatomical variations, and deliverable as a once-daily tablet would fill a gap that the field has pursued for decades without success. Sulthiame's Lancet trial does not prove it is that agent — Phase 2 trials are not powered for definitive efficacy conclusions — but it demonstrates that the pharmacological target is real and that meaningful effect sizes are achievable.
Frequently Asked Questions
What is sulthiame and how does it work for sleep apnea?
Sulthiame is a carbonic anhydrase inhibitor currently approved in several European countries for childhood epilepsy. For sleep apnea, it appears to work by increasing respiratory drive — the brain's signal to breathe — stabilizing breathing control during sleep and reducing the likelihood of upper airway collapse. It is an investigational drug for sleep apnea and has not been approved for this indication in the U.S. or Canada.
What did the Lancet trial find?
A multicenter, double-blind, randomized, placebo-controlled Phase 2 trial of 298 adults with moderate-to-severe OSA found that higher doses of sulthiame reduced breathing interruptions during sleep by up to 47% and improved overnight oxygen levels compared to placebo. Side effects were mostly mild and temporary.
Can I get sulthiame for sleep apnea?
Not yet. Sulthiame is not approved for sleep apnea anywhere in the world. It is an investigational drug for this indication. The Lancet trial was a Phase 2 dose-finding study; Phase 3 confirmatory trials would be needed before any regulatory approval.
Is this better than CPAP?
It cannot be directly compared based on current data. CPAP, when used consistently, typically reduces the AHI by 80–90% in most patients. Sulthiame reduced AHI by up to 47% in the Phase 2 trial. However, a 47% reduction in a patient who would otherwise stop using CPAP entirely may represent a better clinical outcome than 80% reduction on paper in a device the patient doesn't actually use.
What are the next steps for sulthiame as a sleep apnea treatment?
Phase 3 clinical trials would be required to confirm efficacy, establish the optimal dose, characterize the full safety profile, and generate data needed for regulatory applications. As of mid-2026, no Phase 3 trial dates have been announced publicly.
