Ambien Appears to Remedy Central Sleep Apnea

[robbieh]

From MedPage Today: http://www.medpagetoday.com/PrimaryCare ... s/tb2/3594

Ambien Appears to Remedy Central Sleep Apnea

By Michael Smith, MedPage Today Staff Writer
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
June 22, 2006

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.

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.

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[Slinky]

Thanks for the headsup and info, robbieh.

I assume that the reference to "commercial supporter" was the maker of Ambien who has a vested interest in these results.

[robbieh]

Is hard to say... I am a nurse case manager and read tons of articles daily to keep up with what is being put forth in the medical literature. It is valuable to read them all because that is what is affecting our health care, whether or not it is accurate. This particular source of information seems to be reliable and they list the author's/reasearcher's connections to companies that have an interest in what they are saying.

[Snoredog]

"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?"

mmm.... that seems totally contrary to what the general consenus found here is on the topic, but I guess I haven't read enough hypnograms yet

[christinequilts]

"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?"

mmm.... that seems totally contrary to what the general consenus found here is on the topic, but I guess I haven't read enough hypnograms yet

Doesn't sound contrary to me at all- centrals during sleep onset or post arousal are very common and happen in normal people without any type of sleep apnea. Its only contrary to what you want to believe about centrals always causing an arousal & needing to be avoided at all cost. In most people, its the arousal that causes the central. Its that old changing of O2/CO2 needs across the various stages of sleep and the body needing to catch up with the changes during transition, just like we have to adjust our speed as the speed limit changes. Think of a central as putting on the brakes to meet the lower speed limit.

I have centrals across all stages of sleep, though noticeable less in REM, and rarely have obstructive events (obstructive AHI less then 3-4 compared to central AHI of 60+ on original PSG, with Ambien taken). I made the assumption when I was started on BiPAP ST nearly 4 years ago that my sleep doctor would want me to go off my nightly Ambien, using it only occasionally. He corrected me before too long at a follow up appointment, telling me that most people with CSA need to be Ambien or similar type sleep medication and this was long before this study was published. His explanation was that BiPAP ST works in part by reacting to events when they are already occurring, unlike xPAP for OSA, which prevents apneas before they happen, plus BiPAP ST isn't that great at even treating a central in some cases, like mine. The other reason is that people with CSA tend to remember waking up more often & have poorer sleep quality then similar people with OSA.

I tried different sleep medications as they came out, partly because Ambien can lose its effectiveness and to see if anything else would work better. Nothing ever did, though my sleep was never great, even with Ambien & BiPAP ST. I did experiment with when I took my Ambien, since I take my meds via a feeding tube, which bypasses my stomach, which meant Ambien CR was not an option, but I didn't have to be awake to take the second half of the dose either. It was interesting to see how it affected my nightly Encore Pro data and there was a correlation with when I received & how my stats looked last fall. And how much worse it got when I tried a night or two without any sleep medications, though none of the nights were that great to start with.

Getting into the sleep-wake instability issue, I had a split night PSG last fall, with taking half my Ambien at bedtime & half for second part, but no BiPAP ST for the first couple of hours. The no BiPAP ST portion was a pretty sad excuse for 'sleep'- including descriptions like 'difficult to score sleep' & 'as soon as she had a microsleep, she was awakened by central hypopneas & periodic breathing'. Unfortunately, I was never asleep long enough to even score any of the hypopneas under Medicare guidelines, so I had an AHI of 2 obstructive events for that 2 hours & less then 50% sleep efficiency. Definitely a sleep-wake instability issue. Second part of study with BiPAP ST was a little better, at least I got some sleep, though still very poor quality with plenty of periodic breathing, Alpha Intrusion & excessive cyclic alternating pattern (CAP). When you look at any of my past PSG's, you see solid blocks of time where the graphic for sleep staging looks more like an EGG line then anything else, as it bounces back and forth from wake to stage I sleep after any time I've been awakened fully, for whatever reason, or at sleep onset. Thankfully that pattern only made a brief appearance at the beginning of my Adapt titration.

So is CSA associated with sleep-wake instability, yes- but its not the only issue for most people diagnosed with CSA. Can Ambien help? Sometimes, but its definitely not a replacement for BiPAP ST or ASV. Thankfully with my Adapt, I've been able to decrease my use of Ambien considerably.

Back to the study:

Methods : We conducted an open label trial of zolpidem in 14 patients with newly diagnosed idiopathic central sleep apnea (central apnea-hypopnea index >/=10 and symptoms of snoring and /or excessive daytime sleepiness). Patients were started on zolpidem 10 mg at bedtime. In 11.4 +/- 7.4 weeks a repeat 8 hour polysomnogram and assessment of daytime sleepiness by the Epworth Sleepiness Scale (ESS) were performed.

Results:
On zolpidem the AHI decreased from 32 +/- 21(SD) to 16 +/- 13 (p< 0.005).
Central apnea-hypopnea index decreased from 27 +/- 20 to 9 +/- 14 (p<0.001) without change in obstructive apnea-hypopnea index (pre 5+/-5, with zolpidem 7 +/- 10).
Mean lowest NREM arterial oxygenation saturation was the same (pre 87+/-4%, with zolpidem 87+/-4%).
Sleep efficiency, NREM, REM and slow wave sleep percents did not change. Percent stage 1 sleep decreased from 40+/- 23 to 26 +/- 14 (p<0.003) and percent stage 2 increased from 52 +/- 25 to 64 +/- 16(P<0.001).
ESS improved from 14 +/- 5 to 8 +/- 5 (p<0.002).

The AHI did decrease over all, but only to 16, not the 6 quoted in the article, which is very different result- you still are having a lot of events at 16 per hour. Sleep Efficiency didn't change, though there was more Stage II then stage I sleep. Patients were new to Ambien and retested after several weeks, which has always made me wonder what my AHI might have been if I hadn't already been on Ambien for several years at that point.