Other Agents Used to Treat Obstructive Sleep Apnea See Also Chapter

From the mid 1970s to the 1990s, prior to the FDA approval of modafinil, medications like protriptyline (Vivactil®), imipramine (Tofranil®), medroxyprogesterone (Cycrin®, Provera®), acetazolamide (Diamox®), and theophylline (Theolair®, Uniphyl®) were utilized to improve alertness and daytime functioning in those with OSA. Studies in small numbers of patients showed limited efficacy, usually improving mild to moderate symptoms only. Some studies showed no clinically significant benefit and currently these medications are infrequently used. All are included for the sake of completeness (6,14,15).

Protriptyline, a tricyclic antidepressant (TCA) with activating properties, was studied in doses of 10 to 30 mg every morning to improve wakefulness and decrease apneic episodes. Its proposed mechanism of action is two-fold: reducing rapid eye movement (REM) sleep which in turn reduces the longer oxygen desaturation periods characteristic of REM sleep, and enhancing upper airway tone. Imipramine, a less noradrenergic selective TCA, has demonstrated similar efficacy to protripty-line. Because of their REM suppressant effects, TCAs have been proposed as a reasonable option for individuals with REM-dependent OSA; however, the anticho-linergic and cardiovascular side effects of TCAs outweigh the potential benefits for most individuals (6).

Medroxyprogesterone, a synthetic form of progesterone, is thought to stimulate respiratory drive and improve oxygenation and ventilation in a dose-related manner up to 60 mg/day. Four systematic studies have concluded that it is not beneficial for the majority of patients although one double-blind study showed a reduction of the apnea-hypopnea index (AHI) for a small number of patients (15). Medroxyprogesterone 20 mg three times a day can be considered for OSA patients who do not tolerate CPAP, who refuse surgical treatment, and who are candidates for progesterone therapy for other reasons (e.g., menopause in women, paraphilia in men).

Acetazolamide is a carbonic anhydrase inhibitor that results in the development of metabolic acidosis, which normally augments ventilation. This is how it works to prevent altitude sickness in mountain climbers. The administration of acetazolamide 500 mg to 1000 mg in divided doses reduced the frequency of apneas plus hypopneas in patients with OSA, but there was no decrease in awakenings from sleep and no improved breathing during sleep (14,15). Acetazolamide use is associated with many adverse effects including fatigue, drowsiness, nausea, vomiting, hyperglycemia, hyperuricemia, and electrolyte abnormalities. Due to lack of significant efficacy and poor tolerability, acetazolamide has no place in the routine treatment of OSA (14-16).

Theophylline is a ventilatory stimulant that blocks the ventilatory depressant action of adenosine. In a placebo-controlled trial of theophylline in OSA, there was a significant reduction in obstructive events during sleep (-29%), but sleep quality was significantly worsened by theophylline with more frequent arousals and daytime impairment. Other studies have shown that any potentially beneficial effect on sleep apnea was lost with time in the majority of patients. Theophylline has no place in the routine treatment of persons with sleep apnea (6).

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