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.
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- "Patients with obstructive sleep apnea-hypopnea (OSAH) have abnormal structures and neurobiological mechanisms of the upper airway (Schellenberg et al., 2000; Hsu et al., 2004; Smith et al., 2006; Lee et al., 2010). Understanding the upper airway structure and function in OSAH patients is needed to gain insight into the pathogenesis of this disorder to improve the selection of both appropriate therapies and treatment success (Halme et al., 2010). "
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ABSTRACT: Apnea and the respiratory cycle are dynamic processes in obstructive sleep apnea-hypopnea (OSAH), which occur only during sleep. Our study aimed to observe the dynamic changes in the soft palate and the uvula during wakefulness and sleep using ultrafast magnetic resonance imaging (UMRI) to provide reference data for the pathogenesis and treatment of OSAH. The dynamic changes in the soft palate and uvular tip of 15 male patients (average age: 50.43 ± 9.82 years) with OSAH were evaluated using UMRI of the upper airway while asleep and awake after 1 night of sleep deprivation. A series of midline sagittal images of the upper airway were obtained. The distance from the center of the soft palate to the X-axis (an extended line from the anterior nasal spine to the posterior nasal spine), from the uvular tip to the X-axis, from the center of the soft palate to the Y-axis (a perpendicular line from the center of the pituitary to the X-axis), and from the uvular tip to the Y-axis (designated as PX, UX, PY, and UY, respectively) were measured during sleep and wakefulness. The minimum PX, PY, UX, and UY were shorter during sleep than during wakefulness, whereas the maxima were longer during sleep (P < 0.01), the differences between the maximum and minimum PX, PY, UX, and UY were larger during sleep (P < 0.01). The upward, downward, forward, and backward ranges of movement of the soft palate and the uvular tip were larger during sleep in OSAH patients. This increased compliance may trigger each airway obstructive event.
Available from: Sandra Costa Fuchs
- "The efficacy of CPAP in patients with milder forms of OSA is still unproven , which could be secondary to the low adherence in the use of the method. Other therapies could be beneficial in such patients . "
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ABSTRACT: Obstructive sleep apnea (OSA) and hypertension are well-known cardiovascular risk factors. Their control could reduce the burden of heart disease across populations. Several drugs are used to control hypertension, but the only consistently effective treatment of OSA is continuous positive airway pressure. The identification of a drug capable of improving OSA and hypertension simultaneously would provide a novel approach in the treatment of both diseases.Methods/design: This is a randomized double-blind clinical trial, comparing the use of chlorthalidone with amiloride versus amlodipine as a first drug option in patients older than 40 years of age with stage I hypertension (140 to 159/90 to 99 mmHg) and moderate OSA (15 to 30 apneas/hour of sleep). The primary outcomes are the variation of the number of apneas per hour and blood pressure measured by ambulatory blood pressure monitoring. The secondary outcomes are adverse events, somnolence scale (Epworth), ventilatory parameters and C reactive protein levels. The follow-up will last 8 weeks. There will be 29 participants per group. The project has been approved by the ethics committee of our institution.
The role of fluid retention in OSA has been known for several decades. The use of diuretics are well established in treating hypertension but have never been appropriately tested for sleep apnea. As well as testing the efficacy of these drugs, this study will help to understand the mechanisms that link hypertension and sleep apnea and their treatment.Trial registration: ClinicalTrials.gov: NCT01896661.
Available from: David W Carley
- "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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ABSTRACT: Study Objective: Animal data suggest that Δ(9)-TetraHydroCannabinol (Δ(9)THC) stabilizes autonomic output during sleep, reduces spontaneous sleep-disordered breathing, and blocks serotonin-induced exacerbation of sleep apnea. On this basis, we examined the safety, tolerability, and efficacy of dronabinol (Δ(9)THC), an exogenous Cannabinoid type 1 and type 2 (CB1 and CB2) receptor agonist in patients with Obstructive Sleep Apnea (OSA). Design and Setting: Proof of concept; single-center dose-escalation study of dronabinol. Participants: Seventeen adults with a baseline Apnea Hypopnea Index (AHI) ≥15/h. Baseline polysomnography (PSG) was performed after a 7-day washout of Continuous Positive Airway Pressure treatment. Intervention: Dronabinol was administered after baseline PSG, starting at 2.5 mg once daily. The dose was increased weekly, as tolerated, to 5 mg and finally to 10 mg once daily. Measurements and Results: Repeat PSG assessments were performed on nights 7, 14, and 21 of dronabinol treatment. Change in AHI (ΔAHI, mean ± SD) was significant from baseline to night 21 (-14.1 ± 17.5; p = 0.007). No degradation of sleep architecture or serious adverse events was noted. Conclusion: Dronabinol treatment is safe and well-tolerated in OSA patients at doses of 2.5-10 mg daily and significantly reduces AHI in the short-term. These findings should be confirmed in a larger study in order to identify sub-populations with OSA that may benefit from cannabimimetic pharmacologic therapy.
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