Serotonin and Sleep Apnea See Also Chapter

Serotonin is thought to be a key neurotransmitter involved in the modulation of upper airway tone. The hypoglossal nerve, which supplies the genioglossus muscle, is depolarized by serotonin. During sleep (especially REM sleep), there is a reduction in serotonergic output to the hypoglossal nucleus—suggesting that augmentation of serotonin around the nucleus may increase upper airway tone and improve sleep-disordered breathing. Although animal studies have shown increased genioglossus muscle activity when serotonin activity is augmented on brainstem preparations, the data that this therapy is likely to benefit human patients with OSA are limited (94-96).

Because serotonin does not cross the blood-brain barrier, selective serotonin reuptake inhibitors (SSRIs) have been used to counter the reduction in upper airway muscle activity (which occurs at sleep onset in OSA patients). Sunderram et al. (97) administered paroxetine (Paxil®, Pexeva®) to 11 normal subjects and measured genioglossus electromyography under varying conditions (CPAP, hypercapnia, room air); the use of paroxetine resulted in a significant increase in genioglossus activity suggesting that the drug may be helpful. However, the results in patients with OSA have been disappointing. Berry et al. (98) administered a single dose 40 mg dose of paroxetine to eight men with severe OSA; although peak genioglossus activity increased, there was no effect on the severity of sleep apnea (75 events/hour vs. 74 events/hour for drug vs. placebo, respectively). Kraiczi et al. (99) performed a placebo-controlled crossover trial of paroxetine (20 mg/day) and placebo in 20 patients with OSA. After treatment, there was a significant difference in AHI in the paroxetine versus the placebo group (36 vs. 30 events per hour) but the overall magnitude was small. There was no significant difference in symptoms.

SSRIs cannot presently be recommended as a treatment option for OSA, especially given their potential toxicities (i.e., insomnia, REM suppression, worsened periodic limb movements, increased appetite, serotonin syndrome, and hypo-mania). One possibility is that the amount of serotonergic input into the hypoglos-sal nucleus during sleep may be insufficient for the effectiveness of reuptake inhibitors. As such, direct serotonin agonists (or antagonists acting at autoregulatory presynaptic receptors) may be more effective in treating patients with sleep apnea, and we await future studies in this area (100).

Sleep Apnea

Sleep Apnea

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