Are You Sleeping?

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Do you get enough sleep?

This is what happens to your body if it’s deprived of sleep:

  • You have problems with memory and concentration.
  • You have problems finding the right word.
  • You get irritable – you think so?
  • Neurotransmitters in the brain become altered.
  • You become more susceptible to infection.
  • At its extreme, sleep deprivation can lead to death.

h1sciqsleepwalkingIt seems that no matter how many Ambiens (zolpidem) and Lunestas (eszopiclone) we take, we wake up feeling like shit (sorry – there is just no other word!): feeling hung over and inattentive. So much so that the FDA recently cut recommended doses of Ambien and other drugs that contain zolpidem for fear that their use, even the night before, might impair driving or other activities the next day.

This is because Lunesta and Ambien affect GABA receptors, which are found throughout the brain and are associated with side effects, including thinking disturbances, and deficits in attention and memory, explains Jason Uslaner, lead author of a study published in the April 3 issue of Science Translational Medicine.

A new study funded by Merck (of which Uslaner is director of In Vivo Pharmacology at Merck & Co.) has shown that a new class of sleep medications appears to help people fall asleep without causing grogginess the next day (YES! You did read that correctly!)

These new medications – known as dual orexin receptor antagonists (DORA) – target a more specific region of the brain than the other popular sleep drugs, promoting sleep without affecting cognition.

About 15 years ago, scientists discovered chemical messengers known as orexins, which are released by a relatively small brain region known as the lateral hypothalamus. lateralThis area of the brain releases orexins during the day to keep us awake and lowers levels at night so we can sleep.

The appeal of orexin antagonists, said Dr Michael Thorpy, director of the Sleep-Wake Disorders Center at Montefiore Medical Center in New York City, is that they “target a system that’s more specific for sleep.”

That means, theoretically, fewer side effects and perhaps less of a tendency to be habit-forming, Thorpy explained.

Merck already has one such drug, suvorexant, under review by the FDA.

But with this study, Uslaner and his colleagues investigated a compound called DORA-22, which has the same mechanism of action as suvorexant, to see how it fared alongside Ambien, Lunesta and also diazepam (Valium) in rats and rhesus monkeys.

DORA-22 did not lead to the same mental impairments as the other three drugs. Rhesus monkeys and rats performed just as well on memory and attention tasks shortly after being administered DORA-22 as they did on the placebo.

This is the first time in years that scientists have targeted a totally different receptor in the quest to combat insomnia, said Dr Alexandre Abreu, co-director of the UHealth Sleep Center at the University of Miami Miller School of Medicine.

444-36-cartoonBut many questions remain as even experts note that findings from animal studies do not always hold up in human trials: Do the drugs truly have fewer side effects? Will they be habit-forming? And will they change the quality of sleep in any way?

Those questions will only be answered with more testing and use in humans…(waiting…waiting…waiting…)

 

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More Sleep (on this blog…not for us!)

Good news! The most widely prescribed sleeping pills DO help people get to sleep, but maybe not only because of the medicine, a new study suggests.

Chronic Comic 157When researchers combined studies of some of the newer prescription sleep drugs, they concluded that the drugs owe about half their benefits to a placebo effect. Personally, who cares? If the placebo effect gets me to sleep – that’s fabulous!

But at least one sleep expert disagrees with that conclusion.

AmbienLunesta, and Sonata and their generic versions were all included in the study.

The researchers conclude that these drugs improved people’s ability to fall asleep compared to a placebo; however, the size of the effect was small.

They add that the risk of side effects and the potential for addiction need to be considered when considering using these medications for treating insomnia.

Side effects of sleeping pills can include memory loss (would you actually notice through the fibro fog?), daytime sleepiness, and increased risk of falls, and researchers say the drugs may be especially risky for older patients.

But a sleep specialist says the study does little to convince him that the drugs are less effective than studies suggest.

“The fact is that it is difficult to measure the effectiveness of sleep medications in studies. Patients take them and they either work or they don’t.”

“I don’t see how these researchers can come to the conclusion that 50% of the effect of these sleeping pills are due to the placebo effect,” says David Volpi, MD, of the sleep disorders division of Lenox Hill Hospital in New York.

141. sleep deprivationAccording to researcher A. Niroshan Siriwardena, MD, PhD, one of the major limitations of studies submitted to the FDA is that they failed to measure some of the most troubling issues associated with sleep disturbances including total sleep time, waking after falling asleep, and daytime sleepiness.

“Because the studies didn’t measure these things, we cannot say whether these drugs are useful for improving these outcomes,” he says.

And, Volpi says prescription sleeping pills are often used by patients for much longer than they were originally intended – These drugs are overprescribed and patients stay on them too long, he says.

Siriwardena and Volpi also agree that other types of sleep treatments, such as talk therapy, are underutilized and could be used to help many more patients with sleep issues.

“There are so many things you can try for sleep problems, and cognitive behavioural therapy is one of the best things patients can do to get off of these medication,” Volpi says.

The new analysis, published in BMJ, was a collaborative effort by scientists from the University of Lincoln in the UK, Harvard University, and the University of Connecticut.

It included data from 13 trials submitted by pharmaceutical companies to the FDA for approval of eszopiclone (Lunesta), zaleplon (Sonata), and zolpidem (Ambien).

The studies focused on the time it took to fall asleep after taking the drug.

The new analysis shows that sleeping pill users fell asleep about 22 minutes faster than non-users. Those on placebo fell asleep after 42 minutes.

Prior to publication of this study, the manufacturer of Ambien declined to comment; and the makers of Lunesta and Sonata did not respond.