SLEEP: Ambien Appears to Remedy Central Sleep Apnea

SALT LAKE CITY, June 22 - The sedative Ambien (zolpidem) appears to reduce the symptoms of central sleep apnea, according to a small open-label study reported here.

Patients taking the medication saw both total sleep apnea and central sleep apnea events fall significantly after six weeks of treatment, reported Syed Quadri, M.D., of Henry Ford Hospital at Sleep 2006, the joint meeting of the Sleep Research Society and the American Academy of Sleep Medicine.

The reduction in central apnea events appeared, in turn, to improve several other sleep parameters, including total arousals, sleep latency, and sleep efficiency, Dr. Quadri said.

Central sleep apnea is a rarer condition than obstructive sleep apnea, involving a dysfunction in the brain systems that govern breathing rather than a blockage of the airway. Many patients with central sleep apnea also have some obstructive apnea. In this study, patients were classified as having the central form if they had 10 or more central events an hour, but five or fewer obstructive events.

Because of earlier studies suggesting the sedative-hypnotic drugs might help central sleep apnea, Dr. Quadri and colleagues established a protocol under which eligible central sleep apnea patients were given Ambien for six weeks-10 mg/day 30 minutes before bedtime-after an eight-hour polysomnographic exam.

The polysomnographic exam was repeated at six weeks, Dr. Quadri said. All told, 28 patients were eligible for the study but only 20 completed it.

On treatment, the study found:

• The average total apnea-hypopnea index-including both central and obstructive events-fell from 30 per hour to 13, a difference that was statistically significant at P<0.001.
• Central events fell from 26 per hour to seven a difference that was significant at P<0.001.
• At the same time, the total arousal index fell from 24 to 15 per hour-also significant at P<0.001.

There was a significant linear correlation between the apnea-hypopnea index and total arousal, Dr. Quadri said. However, the researchers performed a covariate analysis, controlling for both central events and total arousal, and found that the change in arousal was no longer significant when they controlled for central events, although central events remained significant when they controlled for arousal.

The implication, Dr. Quadri said, is that "the change in arousal is most likely driven by the change in central events," and that the improvements in other sleep parameters are a function of the change in arousal.

To prove that link will probably take a randomized controlled trial, said Susheel Patil, M.D., of Johns Hopkins in Baltimore, who chaired the session in which Dr. Quadri made his report.

"Central sleep apnea is associated with sleep-wake instability," Dr. Patil said in an interview, "and so it's a little bit of a chicken and egg issue: Is it the central sleep apnea that's leading to the sleep disruption or is it the sleep-wake instability that's leading to the apnea?"

The answer to the conundrum has safety implications, he said, since central sleep apnea patients-if they use a hypnotic drug to control the condition-are likely to be using it for a long time. "It's an issue with using Ambien," he said.