The term 'hypersomnia' describes a group of symptoms that includes severe daytime sleepiness
and sleeping long periods of time (more than 10 hours per night). Sometimes, hypersomnia is
caused by a problem with the quality of sleep occurring at night, for instance when nighttime
sleep is disrupted by frequent breathing pauses. In other cases, however, hypersomnia occurs
even when nighttime sleep is of good quality. These cases of hypersomnia are presumed to be a
symptom of brain dysfunction, and so are referred to as hypersomnias of central (i.e., brain)
origin.
The causes of most of these central hypersomnias are not known. However, our group has
recently identified a problem with the major brain chemical responsible for sedation, known
as GABA. In a subset of our hypersomnia patients, there is a naturally-occurring substance
that causes the GABA receptor to be hyperactive. In essence, it is as though these patients
are chronically medicated with Valium (or Xanax or alcohol, all substances that act through
the GABA system), even though they do not take these medications.
Current treatment of central hypersomnias is limited. For the fraction of cases with
narcolepsy, there are FDA-approved, available treatments. However, for the remainder of
patients, there are no treatments approved by the FDA. They are usually treated with
medications approved for narcolepsy, but sleep experts agree that these medications are often
not effective for this group of patients.
Based on our understanding of the GABA abnormality in these patients, we evaluated whether
clarithromycin (an antibiotic approved by the FDA for the treatment of infections) would
reverse the GABA abnormality. In a test tube model of this disease, clarithromycin does in
fact return the function of the GABA system to normal. The investigators have treated a few
patients with clarithromycin and most have felt that their hypersomnia symptoms improved with
this treatment.
To determine whether clarithromycin is truly beneficial for central hypersomnia, this study
will compare clarithromycin to an inactive pill (the placebo). All subjects will receive both
clarithromycin and the placebo at different times, and their reaction times and symptoms will
be compared on these two treatments to determine if one is superior. If this study shows that
clarithromycin is more effective than placebo in the treatment of hypersomnia, it will
identify a potential new therapy for this difficult-to-treat disorder.