Randomized trial shows sulthiame significantly reduces breathing interruptions in sleep apnea patients — Evidence Review
Published in The Lancet, by researchers from University of Gothenburg
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Table of Contents
A new clinical trial found that sulthiame, a drug previously used for epilepsy, significantly reduced breathing interruptions in people with moderate to severe sleep apnea. Related research generally supports these findings, suggesting sulthiame may offer a promising alternative for patients unable to tolerate mask-based treatments, according to the University of Gothenburg.
- Prior randomized trials have shown that sulthiame can reduce apnea-hypopnea events and improve oxygen levels, supporting the magnitude and direction of effects seen in the new study 1 3.
- Multiple studies confirm that sulthiame is generally safe and well-tolerated, though mild and temporary side effects such as paresthesia are common at higher doses 1 3.
- Existing reviews highlight the challenges in sleep apnea treatment adherence and the need for non-invasive alternatives, with sulthiame representing one of the most robust pharmacological candidates to date 4 5 6.
Study Overview and Key Findings
Obstructive sleep apnea is a prevalent condition with substantial health risks, and many patients struggle to use standard treatments like CPAP masks. The recent multi-country European trial led by researchers at the University of Gothenburg explores the potential of pharmacological intervention using sulthiame, a medication already approved for childhood epilepsy, as an alternative therapy. This study is notable for its size, rigor, and focus on medication-based management in a field dominated by device-driven therapies.
| Property | Value |
|---|---|
| Study Year | 2025 |
| Organization | University of Gothenburg |
| Journal Name | The Lancet |
| Authors | Winfried Randerath, Ludger Grote, Kaj Stenlöf, Ingo Fietze, Julia Chevts, Erik Buntinx, Javier Albares, Katrin Kuhn, Corinna Hansen, Andreas Völp, Jan Hedner, Dries Testelmans, Jean-Benoit Martinot, Farhad Baharloo, Benny Gimbada Mwenge, Erik Buntinx, Pierre Philip, Jean Louis Pepin, Frederic Gagnadoux, Maxime Patout, Maria Fernanda Troncoso Acevedo, Alejandro Iranzo de Riquer, Francisco Martinez-Orozco, Francisco Javier Puertas Cuesta, Ainhoa Alvarez Ruiz de Larrinaga, Francisco Javier Albares Tendero, Christian Viniol, Winfried Randerath, Heike Benes, Ingo Fietze, Geert Mayer, Katrin Gade, Christian Deckert, Peter Heymer, Frank Kaessner, Julia Chevts, Henning Candler, Zbysek Pavelek, Samuel Genzor |
| Population | Individuals with moderate to severe sleep apnea |
| Sample Size | n=298 |
| Methods | Randomized Controlled Trial (RCT) |
| Outcome | Breathing interruptions, sleep quality, oxygen levels |
| Results | Higher doses of sulthiame reduced breathing interruptions by up to 47% |
Literature Review: Related Studies
To situate this research within the broader scientific context, we searched the Consensus database, which indexes over 200 million research papers. The following queries were used to identify relevant studies:
- sulthiame sleep apnea treatment effectiveness
- breathing interruptions sulthiame dosage comparison
- non-invasive sleep apnea therapies research
Table: Key Topics and Findings from Related Studies
| Topic | Key Findings |
|---|---|
| How effective and safe is sulthiame for treating obstructive sleep apnea? | - Sulthiame significantly reduces apnea-hypopnea events in moderate to severe OSA and is generally well tolerated, though higher doses may cause mild, temporary side effects 1 2 3. - The drug improves overnight oxygenation and sleep quality, with effect sizes among the strongest reported for pharmacologic OSA treatments 1 2 3. |
| How do pharmacological therapies compare to standard and alternative OSA treatments? | - CPAP remains the gold standard for OSA but has poor long-term adherence rates; mandibular advancement devices (MAD) and positional therapy are less effective but better tolerated 4 5. - Sulthiame is the most promising pharmacological candidate to date, but other alternatives like hypoglossal nerve stimulation and non-invasive laser therapies are also under investigation 5 7 8. |
| What are the remaining gaps and future directions in OSA therapy? | - No current therapy cures OSA, and multidisciplinary, integrated approaches may maximize treatment success 6. - There is a need for long-term studies on sulthiame’s safety, efficacy, and sustained effects, as well as comparative effectiveness with emerging device-based and minimally invasive therapies 3 4 6. |
How effective and safe is sulthiame for treating obstructive sleep apnea?
Multiple randomized trials and mechanistic studies have found that sulthiame can substantially reduce the frequency of breathing interruptions (apnea-hypopnea index) and improve overnight oxygen saturation in patients with moderate to severe OSA. The new study's findings of a 47% reduction in breathing interruptions are consistent with previous results, which reported reductions of 32-41% depending on dosage and study population 1 3. Safety profiles are favorable, with most side effects being mild and temporary, such as paresthesia and occasional dyspnea at higher doses. These data suggest that sulthiame is among the most effective pharmacological treatments examined in OSA to date.
- Prior RCTs demonstrated reductions in apnea-hypopnea index of 32-41% with sulthiame, aligning closely with the new trial’s outcomes 1 3.
- Overnight oxygenation and sleep quality improvements have been observed across multiple studies, reinforcing the consistency of these benefits 2 3.
- Side effects are predominantly mild, with transient paresthesia being most common; serious adverse events are rare 1 3.
- The mechanism of action, targeting carbonic anhydrase, is well supported by mechanistic studies elucidating sulthiame’s impact on respiratory regulation 2.
How do pharmacological therapies compare to standard and alternative OSA treatments?
CPAP remains the most effective intervention for reducing apnea events and improving objective sleep metrics, but it suffers from low long-term adherence due to discomfort and inconvenience 4 5. Mandibular advancement devices and positional therapies are less effective but offer alternatives for mild to moderate cases or those intolerant to CPAP. Pharmacologic treatments like sulthiame represent a new direction for OSA management. While other alternatives, such as hypoglossal nerve stimulation and minimally invasive laser procedures, show promise—especially in CPAP-intolerant populations—sulthiame stands out for its robust effect size in clinical trials 5 7 8.
- CPAP achieves the greatest reduction in apnea-hypopnea index but is discontinued by up to half of patients within a year 4 5.
- Mandibular advancement devices are best suited to mild or moderate OSA, with limited efficacy in severe cases 4 5.
- Sulthiame’s magnitude of effect in RCTs approaches that of some device-based therapies, making it a compelling alternative for specific patient groups 1 3.
- Other non-invasive and minimally invasive treatments, such as hypoglossal nerve stimulation and laser-assisted uvulopalatoplasty, are effective in select populations but require further comparative research 5 7 8.
What are the remaining gaps and future directions in OSA therapy?
Despite advances in both device-based and pharmacological treatments, no current therapy cures OSA, and the multifactorial nature of the disorder complicates management. Reviews emphasize the importance of multidisciplinary, individualized care and ongoing research into new therapies. Large-scale, long-duration studies are needed to assess the durability of sulthiame’s effects, long-term safety, and how it compares in real-world settings to both established and emerging alternatives 3 4 6.
- Multidisciplinary and integrated management approaches may maximize treatment outcomes for OSA 6.
- Long-term data on sulthiame’s sustained efficacy, safety, and patient-reported outcomes are still lacking 3.
- Comparative effectiveness studies are necessary to evaluate sulthiame alongside device-based and minimally invasive therapies 4 6.
- Research into the pathophysiological mechanisms of OSA and how different interventions target these pathways will inform future therapeutic innovation 2 6.
Future Research Questions
Although sulthiame shows promise as a drug-based therapy for obstructive sleep apnea, several important questions remain. Future research should address long-term safety and efficacy, comparative effectiveness with other treatments, patient selection, and the mechanisms by which sulthiame exerts its therapeutic effects.
| Research Question | Relevance |
|---|---|
| What are the long-term safety and efficacy outcomes of sulthiame in patients with obstructive sleep apnea? | Most existing studies are short-term; long-term data are needed to assess sustained benefits, side effects, and risks associated with chronic use of sulthiame 1 3. |
| How does sulthiame compare to CPAP and other non-invasive therapies in terms of effectiveness and adherence? | Direct comparisons are lacking; understanding relative benefits and patient adherence will inform clinical guidelines and individualized care 4 5. |
| Which patient subgroups benefit most from sulthiame treatment for sleep apnea? | Identifying characteristics (e.g., OSA severity, comorbidities, previous therapy adherence) linked to better outcomes will enhance patient selection 3 5. |
| What are the mechanisms by which sulthiame improves breathing regulation in sleep apnea? | Elucidating the drug’s action on respiratory physiology and carbonic anhydrase inhibition can guide further drug development and optimization 2. |
| How does sulthiame treatment impact cardiovascular and metabolic outcomes in OSA patients? | Since untreated OSA increases risk for cardiovascular disease and diabetes, it is important to determine whether sulthiame improves these long-term health outcomes 4 6. |
This article summarizes current evidence on sulthiame as a potential drug therapy for obstructive sleep apnea, situating the new trial in the context of related research and identifying key directions for future investigation.