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Area of Science:

  • Sleep Medicine
  • Pharmacology
  • Respiratory Medicine

Background:

  • Carbonic anhydrase inhibitors can reduce apnoeic events in sleep disordered breathing.
  • Zonisamide is a carbonic anhydrase inhibitor known to induce weight loss in obese patients.
  • Both properties may potentially alleviate obstructive sleep apnoea (OSA).

Purpose of the Study:

  • To investigate the influence of zonisamide's carbonic anhydrase inhibition and weight loss effects on obstructive sleep apnoea (OSA).
  • To compare the efficacy of zonisamide with placebo and continuous positive airway pressure (CPAP) in treating moderate-to-severe OSA.

Main Methods:

  • A randomized controlled trial involving 47 patients with moderate-to-severe OSA (BMI 27-35 kg·m⁻²).
  • Participants received zonisamide, placebo, or CPAP for 4 weeks, followed by an open extension comparing zonisamide and CPAP for 20 weeks.
  • Evaluations included polysomnography, biochemistry, and symptom assessment.

Main Results:

  • Zonisamide significantly reduced the apnoea/hypopnoea index (AHI) by 33% and oxygen desaturation index by 28% compared to placebo (p=0.02 and p=0.014).
  • At 24 weeks, zonisamide showed a 13% AHI reduction (compliance adjusted), while CPAP achieved 61% (p=0.001).
  • Zonisamide led to a weight reduction of -2.7 kg, whereas CPAP increased weight by 2.3 kg (p<0.001) at 24 weeks. Zonisamide also decreased bicarbonate levels.

Conclusions:

  • Zonisamide reduces OSA, potentially through carbonic anhydrase inhibition mechanisms, independent of significant body weight changes.
  • The therapeutic effect of zonisamide on OSA was less pronounced than that of CPAP.
  • Zonisamide is associated with more frequent side-effects compared to placebo and CPAP.