title: Zonisamide reduces obstructive sleep apnoea: a randomised placebo-controlled study.
abstract: Carbonic anhydrase inhibition reduces apnoeic events in sleep disordered breathing. Zonisamide inhibits carbonic anhydrase, and induces weight loss in obese patients. This study explored the relative influence of these two properties, which may both alleviate obstructive sleep apnoea (OSA). Continuous positive airway pressure (CPAP) was used as a standard care comparator. 47 patients with moderate-to-severe OSA and a body mass index of 27-35 kg·m(-2) were randomised to receive either zonisamide, placebo or CPAP for 4 weeks. The open extension phase (20 weeks) compared CPAP and zonisamide. Polysomnography, biochemistry and symptoms were evaluated. At 4 weeks, zonisamide reduced apnoea/hypopnoea index (AHI) by a mean±sd 33±39% and oxygen desaturation index by 28±31% (p=0.02 and 0.014, respectively; placebo adjusted). The mean compliance adjusted reduction of AHI after zonisamide and CPAP was 13 and 61%, respectively, (p=0.001) at 24 weeks. Body weight was marginally changed at 4 weeks, but reduced after zonisamide and increased after CPAP at 24 weeks (-2.7±3.0 kg versus 2.3±2.0 kg, p<0.001). Zonisamide decreased bicarbonate at 4 and 24 weeks. Side-effects were more common after zonisamide. Zonisamide reduced OSA independent of body weight potentially by mechanisms related to carbonic anhydrase inhibition. The effect was less pronounced than that obtained by CPAP.
authors.affiliation: Center for Sleep and Vigilance Disorders, Dept of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg.
authors.forename: Davoud
authors.initials: D
authors.lastname: Eskandari
authors.affiliation: Center for Sleep and Vigilance Disorders, Dept of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg.
authors.forename: Ding
authors.initials: D
authors.lastname: Zou
authors.affiliation: Center for Sleep and Vigilance Disorders, Dept of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg.
authors.forename: Mahssa
authors.initials: M
authors.lastname: Karimi
authors.affiliation: Sahlgrenska Center for Cardiovascular and Metabolic Research, Dept of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Stenlöf
authors.affiliation: Center for Sleep and Vigilance Disorders, Dept of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg.
authors.forename: Ludger
authors.initials: L
authors.lastname: Grote
authors.affiliation: Center for Sleep and Vigilance Disorders, Dept of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg jan.hedner@lungall.gu.se.
authors.forename: Jan
authors.initials: J
authors.lastname: Hedner
mesh_terms: D000368:Aged; D000886:Anthropometry; D015992:Body Mass Index; D001835:Body Weight; D002257:Carbonic Anhydrase Inhibitors / Q000627:therapeutic use*; D002256:Carbonic Anhydrases / Q000378:metabolism; D045422:Continuous Positive Airway Pressure; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010919:Placebos; D017286:Polysomnography; D012890:Sleep; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy*; D015431:Weight Loss; D000078305:Zonisamide
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007555:Isoxazoles; D010919:Placebos; D000078305:Zonisamide; D002256:Carbonic Anhydrases