Other drug therapies

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Tricyclic antidepressants

There may be some amelioration of sleep-disordered breathing in OSA patients treated with tricyclic antidepressants, such as protriptyline and imipramine, possibly through a REM stage-restricting effect [68, 69]. Improvement in the OSA symptom of daytime sleepiness, independent of any effect on sleep quality or architecture, has been reported in some studies with protriptyline [70]. However, a recent Cochrane Systematic Review comparing studies using protriptyline and placebo found no significant advantage for the active drug in terms of AHI or any other objective measure of respiratory disturbance in sleep [70].

Sex steroids

There are compelling epidemiological reasons to consider the possibility that hormone replacement therapy in postmenopausal women with OSA, and use of anti-androgens in males with OSA, may be of therapeutic benefit. However, the results of such interventions in therapeutic trials have been disappointing [71]. However, the administration of medroxyprogesterone (MPG) to patients with the most severe form of OSAS, the obesity hypoventilation syndrome in which daytime hypercapnia and nocturnal/sleep hypoventilation are integral clinical features, produces a beneficial ventilatory stimulant effect [71]. In contrast, a single placebo-controlled study of ten male patients with OSA treated with MPG did not demonstrate any difference in measured outcomes of AHI or total sleep time [72]. Furthermore, the significant range of adverse effects of this agent severely limit its applicability.

There are no studies that show convincingly that hormone replacement therapy reduces sleep apnea severity in postmenopausal women with OSA [73-76].

Anti-hypertensive agents

Chronic systemic hypertension is certainly a common association of OSA. Acute blood pressure rises also occur during termination of apneas. Short-term trials of antihypertensives in OSA have had varying modest effects on indices of sleep-disordered breathing. Cilazapril, an ACE inhibitor, and the ^-blocker metoprolol both reduce AHI by about 30% in OSA patients [77]. Some calcium antagonists (isradepine, mibefradil) have also been shown to have similar modest beneficial effect in small numbers of OSA patients [78,79]. The a adrenergic agonist clonidine reduced OSA features in REM sleep in six of eight patients, but not in NREM, and overall there was no significant difference in AHI or overnight minimal oxygen saturation [80]. On a cautionary note, in a few patients in these trials of anti-hypertensives there was actually worsening of OSA features [78, 80].


The cholinesterase inhibitor physostigmine has been investigated in a small blinded, placebo-controlled study of moderate to severe OSA patients, and via steady-state intravenous infusion been shown to modestly decrease the overall AHI and severity of oxygen desaturation, predominantly in REM compared with NREM sleep [81]. The exact mechanism of the beneficial action of physostigmine in sleep apnea is not clear.

Novel therapy

A novel approach to the treatment of OSA has used the intrapharyngeal application of an exogenous surfactant preparation, which lowers the surface tension of upper airway lining liquid and thereby reduces upper airway opening and closing pressures. In a small group of severe OSA patients the measured fall in surface tension was correlated with a significant though small reduction of respiratory disturbance index [82].

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Sleeping Sanctuary

Sleeping Sanctuary

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