A Cochrane review [Abstract] 1 included 35 studies of 25 drugs with a total of 516 subjects. Acetazolamide, eszopiclone, naltrexone, nasal lubricant (phosphocholinamine) and physiostigmine were administered for 1 to 2 nights only. Donepezil in patients with and without Alzheimer's disease, fluticasone in patients with allergic rhinitis, combinations of ondansetrone and fluoxetine and paroxetine were studies of 1 to 3 months duration. The primary outcomes for the systematic review were the apnoea hypopnoea index (AHI) and the level of sleepiness associated with obstructive sleep apnoea (OSA), estimated by the Epworth Sleepiness Scale (ESS). AHI was reported in 25 studies and of these 10 showed statistically significant reductions in AHI.
Intranasal fluticasone in patients with allergic rhinitis was well tolerated and reduced the severity of sleep apnoea compared with placebo (AHI 23.3 versus 30.3; P < 0.05) and improved subjective daytime alertness. Excessive sleepiness was reported to be altered in 4 studies, however the only clinically and statistically significant change in ESS of -2.9 (SD 2.9; P = 0.04) along with a small but statistically significant reduction in AHI of -9.4 (SD 17.2; P = 0.03) was seen in patients without Alzheimer's disease receiving donepezil for 1 month. In 23 patients with mild to moderate Alzheimer's disease donepezil led to a significant reduction in AHI (donepezil 20 (SD 15) to 9.9 (SD 11.5) versus placebo 23.2 (SD 26.4) to 22.9 (SD 28.8); P = 0.035) after 3 months of treatment but no reduction in sleepiness was reported. High dose combined treatment with ondansetron 24 mg and fluoxetine 10 mg showed a 40.5% decrease in AHI from the baseline at treatment day 28. Paroxetine was shown to reduce AHI compared to placebo (-6.10 events/hour; 95% CI -11.00 to -1.20) but failed to improve daytime symptoms. Promising results from the preliminary mirtazapine study failed to be reproduced in the 2 more recent multicentre studies and, moreover, the use of mirtazapine was associated with significant weight gain and sleepiness. Few data were presented on the long-term tolerability of any of the compounds used.
Comment: The quality of evidence is downgraded by study limitations (unclear allocation concealment and blinding), by indirectness (differences between the outcomes of interest and those reported: only short-term outcomes reported), and by imprecise results (few patients and outcome events).
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