Anesthesiologist Paul Garcia and his colleagues are presenting two posters at the Society of Neuroscience meeting this week, whose findings may raise concerns about two non-stimulant drugs Emory sleep specialists have studied for the treatment of hypersomnia: flumazenil and clarithromycin.
For both, the data is in vitro only, so caution is in order and more investigation may be needed.
With flumazenil, Garcia and colleagues found that when neurons are exposed to a low dose for 24 hours, the cells increase expression of some GABA receptor forms.
This could be part of a mechanism for tolerance. I heard some anecdotes describing how flumazenil’s wake-promoting effects wear off over time at the Hypersomnia Foundation conference in July, but it’s not clear how common the phenomenon is.
Flumazenil’s utility in hypersomnia became known after the pioneering experience of Anna Sumner, who has reported being able to use the medicine for years. See this 2013 story in Emory Medicine. Read more
A visitor might not realize this was a meeting devoted to people who experience excessive daytime sleepiness. The 2015 Hypersomnia Foundation Conference on Saturday was full of energy, with:
*more than 245 attendees, about twice as many people as last year’s conference
*medical experts from France, Wisconsin and Louisiana — in addition to Emory
*data from several recent clinical trials
*some signs of industry interest in hypersomnia
Hypersomnia is a sleep disorder in which individuals feel frequent or constant sleepiness and need to sleep for long portions of the day (more than 70 hours per week). It is distinct from other sleep disorders such as narcolepsy and sleep apnea, but its prevalence is still unclear. Conventional stimulants such as amphetamine or modafinil often can be used to treat the sleepiness, but some with hypersomnia find these drugs ineffective or hard to tolerate.
Previous research at Emory has shown that many individuals with hypersomnia have a substance in their spinal fluid that acts like a sleeping pill, enhancing the action of the neurotransmitter GABA. The identity of this mysterious substance is unknown, but Emory researchers report that they are close to identifying it. That could give hypersomnia a “molecular handle” similar to what narcolepsy has, with loss of hypocretin-producing neurons.
The terminology is still up in the air — keynote speaker Isabelle Arnulf from Paris said, “The term ‘idiopathic hypersomnia’ does not mean that you are an idiot.” Rather, she said, it means that even specialists can have trouble distinguishing hypersomnia from other sleep disorders, and “idiopathic” signifies that the detailed cause is still under investigation.
From Emory Medicine, Spring 2013
A small clinical study of clarithromycin for the sleep disorder hypersomnia shows that the antibiotic can combat patients’ subjective experience of sleepiness, but it does not seem to improve reaction time measured in a video-game-type vigilance task.
The effects of clarithromycin in hypersomnia were first observed by Emory doctors when a pioneering patient (Anna Sumner, whose story is told in this Emory Medicine article) unexpectedly experienced sleeplessness when taking it for a respiratory infection.
The results of the study were published online by Annals of Neurology on June 10.
Lynn Marie Trotti, MD, David Rye, MD, PhD and colleagues from the Department of Neurology and Emory Sleep Center conducted the study, which involved 23 patients.
Advantages of clarithromycin:
- It’s inexpensive and widely available.
- It’s an option for people dealing with hypersomnia for whom other medications, such as modafinil, are not helpful or tolerable.
- It represents an alternative to flumazenil, the benzodiazepine antidote that has been shown to help some hypersomnia patients. Flumazenil used to be very scarce, and shortages occur (Hypersomnia Foundation/American Society of Health System Pharmacists).
Disadvantages of clarithromycin:
- It’s an antibiotic, so it probably changes intestinal bacteria.
- Chronic use could promote the growth of antibiotic-resistant bacteria.
- Most patients reported an altered sense of taste or smell. Some describe this as a metallic mouth sensation.
It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After divertingÂ some of these topics into the 2015 crystal ball
,Â I corralledÂ them into themes.
1. Cardiac cell therapy
2. Mobilizing the body’s own regenerative potential
4. Parkinson’s disease therapeutic strategies
(Gary Miller, better packaging for dopamine could avoidÂ stress to neurons).
5. Personal genomics/exome sequencing
, likeÂ Emory’s Robert Gross
and Costas Hadjpanayis, do amazing things
7. Fun vsÂ no fun
Our Web expert
tells me this was Lab Land’s most widely read post last year.
9. Fine-tuning approaches to cancer
Alzheimer’s protein pathology
While a wise Dane once proposed that predictions are dangerous, especially concerningÂ the future, it’s usuallyÂ helpful to plan ahead. Here are five biomedical research topicsÂ we think will occupy our attention in 2015.
1. Alzheimer’s Weâ€™re hearing discordant music coming from Alzheimerâ€™s researchers. Large pharmaceutical companies are shutting down clinical trials in frustration, but researchers keep coming forward with biomarkers that mightÂ predict future disease. This confusing situation calls for some new thinking. Allan Levey, Jim Lah and colleagues have been preparing the way for a â€œbeyond the usual suspectsâ€ look at Alzheimerâ€™s disease. We are looking forward to Leveyâ€™s appearance at the 2015 AAAS meeting and to drug discovery wizard Keqiang Yeâ€™s continuing work on new therapeutic targets.
2. Ebola While the scare over Ebola in the United States may be over (we hope so!), the outbreak continues to devastate countriesÂ in West Africa. Clinical trials testingÂ vaccines and experimental drugs are underway or will be soon. Read more
It’s not sleep apnea. It’s not narcolepsy. Hypersomnia is a different kind of sleep disorder. There’s even an “apples and oranges” T-shirt (see below) that makes that point.
This weekend, your correspondent attended a patient-organized Living with Hypersomnia conference. One of the main purposes of the conference was to update sufferers and supporters on the state of research at Emory and elsewhere, but there was also a lot of community building — hence the T-shirts.
The story of how sleep took over one young lawyer’s life, and how her life was then transformed by flumazenil, a scarce antidote to sleeping pills she was not taking, has received plenty of attention.
Now an increasing number of people are emerging who have a condition similar to Anna Sumner’s, and several questions need answers. Read more
The story of Anna Sumner’s extraordinary experience — disabling chronic sleepiness, leading to scientific discovery and treatment at Emory — has been told in several places, among them the Wall Street Journal and the Today Show.
One of the most extensive and elegant approaches, in our opinion, was science journalist Virginia Hughes‘ post “Re-Awakenings,” originally written for the group blog Last Word on Nothing. (Hughes is now part of National Geographic’s Phenomena quartet of bloggers.) Yesterday “Re-Awakenings” won some recognition, receiving the “Post of the Year” award from ScienceSeeker, a community square for science blogging.
Note: We here at Emory Health Now are still learning about the thriving world of science blogging, but Scientific American’s blog impresario cheap oakley sunglasses Bora Zivkovic calls ScienceSeeker “the main portal for collecting, connecting and filtering science writing online.” The judges for the awards were Fraser Cain, Maggie Koerth-Baker, and Maryn McKenna.
In addition, the most recent issue of Emory Medicine has a feature on Anna’s story, and neurologist David Rye, who leads the Emory team who treated Anna, has his own take in the June issue of Discover magazine.
Posted on May 15, 2013