Zonisamide reduces obstructive sleep apnoea: a randomised placebo-controlled study

• Published in: The European respiratory journal Vol. 44; no. 1; pp. 140 - 149
• Main Authors: ESKANDARI, Davoud, DING ZOU, KARIMI, Mahssa, STENLÖF, Kaj, GROTE, Ludger, HEDNER, Jan
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01-07-2014
• Subjects: ACETAZOLAMIDE; Aged; Anthropometry; Biological and medical sciences; Body Mass Index; Body Weight; Carbonic Anhydrase Inhibitors - therapeutic use; Carbonic Anhydrases - metabolism; CARBONIC-ANHYDRASE; Continuous Positive Airway Pressure; DOUBLE-BLIND; Double-Blind Method; EFFICACY; Female; Humans; INHIBITION; Isoxazoles - therapeutic use; Lungmedicin och allergi; Male; Medical sciences; Middle Aged; OBESE ADULTS; Patient Compliance; Placebos; Pneumology; Polysomnography; Respiratory Medicine and Allergy; Respiratory System; Respiratory system : syndromes and miscellaneous diseases; SCALE; Sleep; Sleep Apnea, Obstructive - drug therapy; THERAPY; VALIDATION; WEIGHT; Weight Loss; Nervous system diseases; Randomization; Sleep apnea syndrome; Respiratory disease; Placebo; Zonisamide
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.00158413

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.