Drug therapy for obstructive sleep apnoea in adults
Abstract
Background
The treatment of choice for moderate to severe obstructive sleep apnoea (OSA) is continuous positive airways pressure (CPAP) via a mask during sleep. However this is not tolerated by all patients and its role in mild OSA is not proven. Drug therapy has been proposed as an alternative to CPAP in some patients with mild to moderate sleep apnoea and could be of value in patients intolerant of CPAP. A number of mechanisms have been proposed by which drugs could reduce the severity of OSA. These include an increase in tone in the upper airway dilator muscles, an increase in ventilatory drive, a reduction in the proportion of REM sleep, an increase in cholinergic tone during sleep, a reduction in airway resistance and a reduction in surface tension in the upper airway.
Objectives
To determine the efficacy of drug therapies in the treatment of sleep apnoea.
Search methods
We carried out searches on the Cochrane Airways Group Specialised Register of trials. Searches were current as of July 2006.
Selection criteria
Randomised, placebo controlled trials involving adult patients with confirmed OSA . We excluded trials if continuous positive airways pressure, mandibular devices or oxygen therapy were used. No restriction was placed upon publication language or trial duration.
Data collection and analysis
Two reviewers independently assessed studies for inclusion, undertook data extraction according to pre‐specified entry criteria, and quality assessment of studies. No response for further information was forthcoming from study authors. Results were expressed as mean differences and 95% Confidence Intervals (CI).
Main results
Twenty‐six trials of 21 drugs, involving 394 participants contributed data to the review. Most of the studies were small and many trials had methodological limitations. Each of the studies states that the subjects had OSA but diagnostic criteria were not always explicit and it is possible that some patients with central apnoeas may have been recruited. Six drugs had some impact on OSA severity and two altered daytime symptoms. One study reported that apnoea hypopnea index (AHI) was lower following treatment with intranasal fluticasone compared with placebo (23.3 versus 30.3) in 24 participants with sleep apnoea and rhinitis. Subjective alertness in the daytime also improved. Physostigmine gave an AHI of 41 compared to 54 on placebo (10 participants) and in a similar study Mirtazipine 15 mg produced an AHI of 13 compared to 23.7 for placebo (10 participants). Topical nasal lubricant given twice overnight resulted in an AHI of 14 compared to 24 with placebo (10 participants). These three latter studies were of single night crossover design and so there are no data on the acceptability of these treatments or their effect on symptoms. Paroxetine was shown to reduce AHI to 23.3 compared to 30.3 for placebo, most of the 20 participants tolerated the treatment but there was no improvement in daytime symptoms. Acetazolamide also reduced the AHI (one crossover trial of nine patients, mean difference 24 (95% CI 4 to 44). However there was no symptomatic benefit from the drug and it was poorly tolerated in the long term. Protriptyline led to a symptomatic improvement (improved versus not improved) in two out of three crossover trials (13 participants, Peto Odds Ratio 29.2 (95% CI 2.8 to 301.1) but there was no change in the apnoea frequency. In one trial naltrexone did reduce AHI, but total sleep time favoured placebo. No significant beneficial effects were found for medroxy progesterone, clonidine, mibefradil, cilazapril, buspirone, aminophylline, theophylline doxapram, ondansetron or sabeluzole.
Authors' conclusions
There is insufficient evidence to recommend the use of drug therapy in the treatment of OSA. Small studies have reported positive effects of certain agents on short‐term outcome. Certain agents have been shown to reduce the AHI in largely unselected populations with OSA by between 24 and 45%. For fluticasone, mirtazipine, physostigmine and nasal lubricant, studies of longer duration are required to establish whether this has an impact on daytime symptoms. Individual patients had more complete responses to particular drugs. It is likely that better matching of drugs to patients according to the dominant mechanism of their OSA will lead to better results and this also needs further study.
PICOs
Plain language summary
Drug therapy for obstructive sleep apnoea in adults
Obstructive sleep apnoea (OSA) is caused by collapse of the upper airway. The mainstay of medical treatment is continuous positive airways pressure (CPAP) delivered through a mask during sleep. Drug therapy has been proposed for patients with mild OSA and those intolerant of CPAP. Many drugs have been tested as treatments for obstructive sleep apnoea (when breathing stops during sleep). Most have not been found to be effective. A few have been shown to reduce the number of apnoeic episodes during sleep but have not yet been shown to improve well‐being during wakefulness. We searched and reviewed all randomised placebo controlled trials of drugs in adult patients with OSA . Most of the trials had methodological flaws. Of 21 drugs tested, eight had some impact on the severity of OSA (in terms of either markers of sleep quality or symptoms of sleepiness) although in most people changes were only modest. Physostigmine, Mirtazipine and nasal lubricant were only trialed on single night studies and the long‐term effects are therefore unknown. Topical nasal steroid was tolerated, reduced the severity of sleep apnoea and improved subjective daytime alertness in a specific sub group with both OSA and rhinitis. Acetazolamide reduced the number of respiratory events per hour of sleep but did not reduce daytime sleepiness and was poorly tolerated long term. Paroxetine had only a small effect on the amount of OSA and while it was tolerated there was no useful effect on daytime symptoms. In contrast participants reported a symptomatic benefit from protriptyline, but there was no improvement in OSA suggesting a different mechanism for their improved sense of well‐being.
