Abstract
BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) is a common condition, featured by repetitive upper airway collapse during sleep manifested with poor quality of life and co-morbidities. Although continuous positive airway pressure (CPAP) is the recommended therapy, lack of patient compliance and persistent symptoms often preclude its success. The present study evaluates the effect of acetazolamide in combination with CPAP, and compares this treatment strategy to single therapy using CPAP in moderate to severe OSA. MATERIALS AND METHODS: A parallel-group, open-label randomized controlled trial consisted of 95 subjects diagnosed with moderate to severe OSA. Subjects were randomly allocated in a 1:1 ratio to CPAP plus acetazolamide (C+D) and CPAP alone (C). The baseline characteristics and the apnea-hypopnea index (AHI) metrics were comparable. Following four weeks of intervention, the outcomes measured involved changes in AHI (apnea hypopnoea index), sleep architecture, ODI (oxygen desaturation Index), and other sleep parameters. RESULTS: The combination of CPAP and acetazolamide significantly reduced total AHI (34.69 ± 18.91 events/hour) compared to CPAP alone (45.47 ± 19.09 events/hour, p = 0.0044). AHI also observed significant improvements during non-REM sleep (p = 0.0014). Although no significant difference was found in AHI during REM sleep between the groups (p = 0.6284), the C+D group demonstrated a notable decrease in severe OSA cases and an increase in mild and moderate OSA classifications. Compliance-adjusted AHI was significantly lower in the C+D group (5.67 ± 3.45) compared to the C group (7.67 ± 3.41, p = 0.0034). The C+D group exhibited improved sleep architecture with lower percentages of N1 and N3 sleep stages, and a trend towards increased REM sleep percentage (p = 0.0704). Significant reductions in WASO (p = 0.0404) and ODI (p = 0.0301) were also observed. Both groups reported minimal and comparable side effects, indicating the safety and tolerability of the combination therapy. CONCLUSION: The addition of acetazolamide to CPAP therapy improves efficacy in OSA treatment parameters among moderate-to-severe OSA, reduces total and NREM AHI as well as ODI without an increase in adverse effects. With added pharmacotherapy, the combination therapy represents a potential adjunctive treatment for managing OSA.