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Mayo Clinic Study Shows Melatonin Helps Alleviate Violent Sleep Disorder Symptoms

Date:  2003-09-09

ROCHESTER, Minn. -- A Mayo Clinic study shows that melatonin successfully alleviates many patients' symptoms of REM-
sleep behavior disorder (RBD), a violent sleep condition that manifests during rapid eye movement (REM) sleep, a stage
of deep sleep in which most dreaming occurs.

"Melatonin can be considered as one possible option for RBD," says Brad Boeve, M.D., Mayo Clinic neurologist and sleep
specialist, and the study's principal investigator.

People who experience RBD appear to act out their dreams, in which screaming, yelling, hitting, kicking and jumping out
of bed tend to occur. These behaviors can cause injury to these people or their bed partners.

"Normally in REM sleep, almost every muscle in your body is paralyzed and you don't move," explains Dr. Boeve.
"Therefore, when you have a dream, there's no excessive activity and no potential for injury. In this disorder, for
reasons we don't fully understand yet, that normal paralysis is lost, and people will appear to act out their dreams.
Sometimes, they're pleasant dreams. Usually, they're nightmarish, violent dreams with the person being chased or
attacked by something or someone. So, they try to defend themselves or fight against it, leading to punching and
kicking. They can injure themselves by jumping out of bed, striking the bedposts or diving out of bed. As for their bed
partners -- they often get injured."

Dr. Boeve describes the potential injuries from RBD as "pretty violent" and points out the issues faced by bed partners
of RBD patients.

"Many of them -- if they've been hit enough times or have been bruised or injured -- do move out of the bed," says Dr.
Boeve. "But, like most couples, they want to sleep together."

Due to undesirable side effects of the current standard treatment for RBD, clonazepam, Dr. Boeve and colleagues sought
to test other drugs to treat this condition. A small European study showing some success in treating RBD patients with
melatonin and the personal story of a Mayo Clinic patient who tried melatonin on his own for RBD and experienced
success, convinced the Mayo Clinic researchers that supplementing was worth studying.

The Mayo Clinic study was conducted retrospectively with 15 consecutive patients treated with melatonin at Mayo Clinic;
findings about the treatment of 14 of them were analyzed. All but one of the patients were male. All of these patients
had another neurologic disorder such as Lewy body dementia, Parkinson's disease or narcolepsy. Of these patients,
eight, or 57 percent, found melatonin treatment successful for a year or more. For two patients, melatonin was
ineffective, including one patient for whom melatonin increased both the frequency and severity of RBD episodes.

"There are gradations in frequency and severity of RBD episodes, and how effective melatonin is for RBD," says Dr.
Boeve. "For some people, RBD happens every night. For others, it happens at least two or three nights per week. So, on
the nights that would be bad, these patients have much better sleep, and therefore their dreams aren't as active or as
violent. They find the nightmare quality of their dreams decreases, and they have far less tendency to punch and kick.
Therefore, the potential for injury to themselves and their bed partners is reduced."

Only five, or 36 percent, of the patients who took melatonin for RBD experienced infrequent, minor side effects such as
headaches or sleepiness in the morning, all of which stopped when the amount of medication prescribed was reduced.

The reason melatonin is effective for some RBD patients remains a mystery to the researchers.

"Melatonin is a naturally-occurring hormone that all of us has -- it rises at night and has sleep-promoting effects,"
says Dr. Boeve. "It has been shown to be helpful in jet lag. Although we were hopeful that melatonin would be helpful
in treating insomnia, most people do not find that it helps much. Why this would decrease RBD -- we don't know. There
isn't a sound theoretical reason why it works."

Even though melatonin is available at drugstores over-the-counter, Dr. Boeve and colleagues would not advocate self-
medicating for RBD. He suggests that patients confer with a sleep specialist and get a proper diagnosis first,
especially because the symptoms of RBD can be mistaken for sleep apnea, which is treated differently than RBD. Patients
also may have other sleep disorders that can be diagnosed and treated. Furthermore, Dr. Boeve points out that it is
critical for patients to be evaluated and treated appropriately, because RBD is associated with certain neurologic
disorders and the diagnosis may have implications for one's future health care.

"First, it's important to recognize RBD is a diagnosable and treatable disorder," says Dr. Boeve. "Therefore, if a
person has violent dreams or acts out the dreams, it is worthwhile to see a clinician for this. If there is potential
for injury, then a patient should be evaluated -- see a sleep clinician and undergo a sleep study for diagnosis and
treatment. You want to make sure you know what you are treating, and then you can decide how to manage it. Importantly,
since some patients with RBD develop dementia or Parkinsonism years later, a neurologist should follow them so that
treatment can be started early if cognitive or motor symptoms develop. This will become increasingly important as
better treatments are developed for dementia and Parkinsonism."

Before advocating widespread usage of melatonin for RBD, Dr. Boeve and colleagues would like to see a prospective,
double-blind, placebo-controlled study conducted with RBD patients.

There is no established incidence or prevalence of RBD at present. According to Dr. Boeve, it is primarily a male
disorder; 80 to 90 percent of RBD patients are male. Although some patients develop the disorder in their 20s or 30s,
Dr. Boeve indicates it usually manifests in males in their 40s, 50s, 60s and 70s. There is no known association between
smoking or obesity and RBD.

"People think RBD is rare, but those of us who see many RBD patients even within our local community, believe it is
quite likely that this disorder is far more common that we have appreciated up to this point," says Dr. Boeve.

The findings of this study were published in the July 2003 issue of Sleep Medicine,
http://www.elsevier.com/locate/sleep

This story has been adapted from a news release issued by Mayo Clinic.

SOURCE: Mayo Clinic / Science Daily
http://www.sciencedaily.com/releases/2003/09/030909070413.htm

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