Drug therapy for obstructive sleep apnoea in adults

Papworth Hospital NHS Foundation Trust, Papworth, England, United Kingdom
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 02/2006; DOI: 10.1002/14651858.CD003002.pub2
Source: PubMed

ABSTRACT 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.
To determine the efficacy of drug therapies in the treatment of sleep apnoea.
We carried out searches on the Cochrane Airways Group Specialised Register of trials. Searches were current as of July 2005.
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.
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).
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.
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.

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    • "Pharmacologic treatment for Obstructive Sleep Apnea (OSA) is limited (Smith et al., 2006), due to the complexity of the neurochemical control and neuromodulation of central respiratory drive and the upper airway motor output (Carley and Radulovacki, 2008). Nevertheless, the poor tolerance and long-term adherence to Continuous Positive Airway Pressure (CPAP) treatment in OSA (Weaver and Grunstein, 2008), make discovery of such therapeutic alternatives clinically relevant and important. "
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    • "Future trials of MAD designs need to be assessed according to agreed success criteria in order to guide clinical practice as to which design of OAs may be the most effective in the treatment of OSA. avoidance, and alteration of sleeping position (Shneerson and Wright, 2001; Smith et al., 2006), a range of upper airway surgical procedures (Bridgman and Dunn, 2000; Sundaram et al., 2005), pharmacological regimen (Smith et al., 2006; Jayaraman et al., 2008), and continuous positive airway pressure (CPAP; Weaver and Chasens, 2007). CPAP is the current treatment of choice as it has been successfully used to treat the symptoms of the majority of OSA patients (Elshaug et al., 2007); however, its efficacy is highly reliant on patient compliance. "
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