Sulthiame safe to use for moderate to severe Obstructive sleep apnea
New research found that Sulthiame is safe and demonstrated a good safety profile in moderate and/or severe obstructive sleep apnea (OSA) by reducing the more than 20 events/h of OSA on average. The trial results were published in the journal American Journal of Respiratory and Critical Care Medicine.
Obstructive sleep apnea (OSA) is characterized by frequent episodes of airway collapse, deranged blood gases, autonomic activation, and sleep fragmentation. Multiple therapies have been developed for OSA but there is not much data on efficacy, compliance, or tolerability. In the recent past individualized therapies, which identify the phenotypic variants have also been developed for OSA. One such management method is the pharmacological inhibition of the carbonic anhydrase (CA) enzyme. Sulthiame which is a CA inhibitor commonly used for epilepsy has been found to cause respiratory stimulation due to CA inhibition. Hence, researchers from Sweden and Germany conducted a study to explore the safety and tolerability of the carbonic anhydrase inhibitor sulthiame (STM) in OSA.
Between February 2018 and December 2019, the 4-week double-blind, randomized, placebo-controlled dose-guiding trial was conducted in patients with moderate and/or severe OSA not tolerating positive airway pressure treatment. The primary outcome of measurement was to evaluate the safety and tolerability of 4 weeks of treatment with STM in patients with moderate to intermittent OSA. Measures of sleep apnea intensity, oxygenation, sleep quality, and patient-related outcomes constituted secondary outcomes.
Findings of the study:
- Intermittent paresthesia was reported by 79%, 67%, and 18% of patients receiving 400 mg STM (n = 34), 200 mg STM (n = 12), and placebo (n = 22), respectively.
- Dyspnea was reported after 400 mg STM (18%).
- Six patients who were from the higher dose group withdrew because of adverse events but there were no serious adverse events.
- The apnea–hypopnea index was reduced from 55.2 to 33.0 events/h (−41.0%) in the 400-mg group and from 61.1 to 40.6 events/h (−32.1%) after 200 mg (P < 0.001 for both) by using STM.
- Corresponding placebo values were 53.9 and 50.9 events/h (−5.4%).
- The apnea–hypopnea index reduction threshold of ⩾50% was reached in 40% of patients after 400 mg, 25% after 200 mg, and 5% after placebo.
- Mean overnight oxygen saturation improved by 1.1% after 400 and 200 mg (P < 0.001 and P = 0.034, respectively).
- There was no change noticed in the Patient-related outcomes.
This is one of the strongest trials that explored the potential pharmacological therapy in OSA. But large-scale clinical studies are needed to justify the usage of STM in OSA.
Further reading: Hedner J, Stenlöf K, Zou D, et al. A Randomized Controlled Clinical Trial Exploring Safety and Tolerability of Sulthiame in Sleep Apnea. Am J Respir Crit Care Med. 2022;205(12):1461-1469. doi:10.1164/rccm.202109-2043OC
