N24HSWD

Contributor Lynne Lamberg – Improving Sleep and Alertness in the Blind: A 5-part Series: Part 5

Part 5 – Research in progress: melatonin-like medications

The recognition that melatonin can shift the timing of inner clocks has triggered efforts to develop melatonin-like medications.

“These medications potentially may prove as good as, or even more effective than melatonin, and could be regulated, prescribed, controlled, and monitored for safety,” said Harvard neuroscientist Steven Lockley.

In 2005, the FDA approved a melatonin-like medication, ramelteon, for the treatment of insomnia characterized by difficulty falling asleep. Researchers report it helped insomniacs fall asleep faster and stay asleep longer, without experiencing a daytime hangover or grogginess, or prompting dependence on its use. The National Library of Medicine provides information on this medication at http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000321/.

In 2010, the FDA granted orphan drug status to another melatonin-like investigational medication, tasimelteon, for use in totally blind adults with N24HSWD. FDA gives orphan drug status to drugs developed specifically to treat rare medical conditions.

A randomized clinical trial now underway will assess the safety and efficacy of tasimelteon in increasing total nighttime sleep time in totally blind adults with N24HSWD. In this trial, researchers will compare tasimelteon with a placebo, that is, a look-alike but inactive pill, over a six month study period.

The study is being conducted at 25 medical centers in the US and six in Germany. It is sponsored by Vanda Pharmaceuticals. Researchers hope to enroll a total of 100 participants: 50 in the active medication group, and 50 in the placebo group.

More information about the study is available at http://24sleepwake.com/, or at http://clinicaltrials.gov/ by searching on “N24HSWD.”

More information about sleep and sleep disorders is available at:

The National Institutes of Health:
http://www.nhlbi.nih.gov/health/public/sleep/

The National Sleep Foundation:
http://www.sleepfoundation.org/

The American Academy of Sleep Medicine:
http://yoursleep.aasmnet.org/

An important reminder: Poor sleep always warrants a discussion with your primary care physician. Keep a sleep diary for at least two weeks before the visit to give your doctor a better understanding of how you sleep.

Record when you go to sleep and get up, and the time of daytime naps. Note use of caffeine, alcohol, and other medications.

Your doctor may refer you to a sleep disorders center. Sleep specialists can assess your melatonin secretion pattern, suggest treatment strategies to improve both sleep and daytime alertness, and tell you about research studies in progress in which you may wish to participate.

This series was written by medical journalist Lynne Lamberg, co-author of The Body Clock Guide to Better Health, http://bodyclockguide.com/. Lamberg writes widely on sleep medicine and biological clocks for physicians and the general public.

Contributor Lynne Lamberg – Improving Sleep and Alertness in the Blind – A Five Part Series: Part 4

Part 4 – Developing New Tactics for Treatment

Karen Karsh, a Denver-based singer, songwriter, and pianist, has a busy schedule—too busy, she insists, to be stalled by sleepless nights and foggy days. The chair of the board of the American Council for the Blind of Colorado, Karsh, 59, has been blind since birth.

“I haven’t officially been diagnosed with N24HSWD,” said Karsh, “but I have every symptom.

“At times I sleep normally, and at other times, I awaken frequently,” she reports. “When I’m exhausted in the daytime, I can’t just fight it. I need to nap.

“My sense is that as I get older, these problems get worse.”

A professional singer since she was 15, Karsh has performed with the Colorado Symphony Orchestra and recorded for ABC Dunhill Records. Her website, http://www.karenkarsh.com/, offers samples from her latest CD.

Karsh has served as an artist in residence for the Denver public school system for 30 years, teaching songwriting.

She also talked her way into a job as an on-camera television reporter. She created and hosted a weekly feature called “Unsung Heroes” for Denver’s KUSA-9News for three and a half years. The program received Gannett Broadcasting’s Innovation of the Year award in 1992.

Karsh is married and the mother of a 25-year-old son. With her professional, volunteer, and family commitments, her schedule often includes late nights and early mornings.

If sleep persistently proves elusive, she may take a sleeping pill to break the cycle. “It’s tough to go without sleep night after night,” she declares. Her physician eased her concerns that occasional use of a sleeping pill would prompt dependence on such medication.

She tried melatonin a few times without finding it helpful. She concedes she did not try it in a systematic way, or know the best time to take it.

Research in progress seeks to determine which blind people are most likely to benefit from taking melatonin, what doses are appropriate, when in the cycle it works best to stabilize rhythms, and whether it has acute or long term adverse effects.

A five-year study that began in 2008, funded by the National Eye Institute (NEI), aims to describe the variability of body rhythms in blind individuals, and to assess the efficacy of 0.025 mg to 20 mg doses of melatonin in synchronizing body clocks with the 24-hour day. Researchers hope to enroll 200 participants. More information is available at http://clinicaltrials.gov/ct2/show/NCT00686907.

Recent work suggests smaller doses of melatonin may lock or entrain rhythms to the 24-hour day as well as or better than larger doses, said Jonathan Emens of Oregon Health and Science University, one of the NEI study investigators. Smaller doses, such as 0.3 or 0.5 mg, he said, may give the body a more discrete time signal than larger doses.

In the US, melatonin can be sold as a dietary supplement. The US Food and Drug Administration (FDA) has not approved its use for the treatment of any medical disorder, and does not regulate its sale. Some other countries, including the United Kingdom, most European countries, Canada, Australia, and New Zealand, regulate melatonin as they do other hormone treatments, and require a prescription for it.

“The medical literature has not produced evidence of significant risk derived from its use,” the American Academy of Sleep Medicine said in guidelines on the clinical evaluation and treatment of circadian rhythm sleep disorders published in 2007. “Thus,” the guidelines state, “the benefits are well supported, and the risks seem low.”

Melatonin’s most commonly reported adverse effects include headaches, nausea, unusually vivid dreams, and daytime grogginess.

Melatonin’s utility in resetting body clocks has spurred development of melatonin-like medications. Part 5 of this report describes some of these medications, and research in progress to assess their safety and efficacy.

Link to Introduction from the Editor: http://www.matildaziegler.com/2011/09/26/letter-from-the-editor-september-26-2011/

Link to Part 1: http://www.matildaziegler.com/2011/10/05/contributor-lynne-lamberg-5-part-series-improving-sleep-and-alertness-in-the-blind/

Link to Part 2: http://www.matildaziegler.com/2011/10/14/contributor-lynne-lamberg-5-part-series-improving-sleep-and-alertness-in-the-blind-2/

Link to Part 3: http://www.matildaziegler.com/2011/10/19/contributor-lynne-lamberg-improving-sleep-and-alertness-in-the-blind-a-five-part-series/

Contributor Lynne Lamberg – Improving Sleep and Alertness in the Blind – A Five Part Series

Part 3: The search for ways to reset inner clocks

Derek Naysmith lost his sight in 1986 when fireworks at a community display misfired and hit him in the face. “I am lucky to have survived,” he said. Both eyes had to be removed. He was 33 years old.

Naysmith, who lives in Edinburgh, Scotland, noticed changes in his sleep pattern almost immediately. “I fell asleep later and awakened later,” he recalls. “Sometimes I fell asleep in the daytime. I moved around the clock roughly every 24 days. I felt grumpy. I was out of phase with my work and my family.”

A lecturer in soil physics before he lost his sight, Naysmith moved into information technology, becoming a computer analyst and designer of data base systems.

A request to members of the British Computer Association of the Blind seeking volunteers for a sleep study at the University of Surrey, in Guildford, connected him with Steven Lockley. Naysmith enrolled in Lockley’s studies, starting around 1995. He completed questionnaires, kept a sleep and mood diary, recorded body temperature, and provided urine samples. This research confirmed that he had N24HSWD

As part of the study, he started taking melatonin, a hormone found to have body-clock resetting properties. “That made life bearable,” Naysmith said.

“I had a young family,” he noted. “Before I started using melatonin, I often missed out on family life. I might have had to go to bed around the time the kids came home from school.”

Now 57 years old, Naysmith continues to rely on melatonin, taking 4 mg. at 9:30 p.m. daily. “I go to bed between 10 p.m. and midnight, get up between 6 and 7 a.m., and have a normal day,” he said.

In his current work as a computer consultant, Naysmith strives to improve web accessibility for visually impaired people. He also devises auditory and tactile ways to convey data from graphs and charts.

Researchers began trying to synchronize the sleep/wake cycle in blind individuals with melatonin supplements in the late 1980s. Previous laboratory research had shown that daily injections of melatonin could synchronize the rhythms of rats kept in constant darkness.

In 1988, biochemist Josephine Arendt and colleagues at the University of Surrey reported they had given melatonin supplements by mouth to a blind man when his natural melatonin secretion started close to his desired bedtime. The melatonin locked his daily schedule of sleeping and waking in place. Subsequent studies showed melatonin supplements could synchronize body clocks in blind individuals.

Melatonin, a naturally-occurring hormone secreted by the pineal gland in the brain, is the biochemical signal of darkness. It serves as an internal marker of whether it is day or night. Because night length changes over the year, melatonin also serves as an internal indicator of whether it is summer or winter.

In sighted individuals, melatonin secretion usually starts several hours before bedtime, typically around 9:30 p.m. to 10 p.m. Melatonin levels stay high through the night, and taper down toward morning. Exposure to light at night turns off melatonin secretion.

Humans are day-active creatures. Melatonin onset tells the body that it is night, and the right time to sleep. When people, sighted or blind, attempt sleep in their biological night, they usually sleep better than they would if trying to sleep in their biological day. Melatonin taken in pill form may induce mild sleepiness. It is especially likely to cause sleepiness if taken in the daytime, when the body does not normally produce melatonin.

The potential of melatonin treatment to help shift workers adjust to schedule changes, travelers flying across multiple time zones to avoid jet lag, and people with other circadian sleep disorders to realign their body clocks is an active focus of current research. In all these situations, the dose of melatonin and time it is taken govern its effects. Some doses and times help body clock adjustment. Others hinder it.

Part 4 of this report discusses additional melatonin research.

Link to Introduction from the Editor: http://www.matildaziegler.com/2011/09/26/letter-from-the-editor-september-26-2011/

Link to Part 1: http://www.matildaziegler.com/2011/10/05/contributor-lynne-lamberg-5-part-series-improving-sleep-and-alertness-in-the-blind/

Link to Part 2: http://www.matildaziegler.com/2011/10/14/contributor-lynne-lamberg-5-part-series-improving-sleep-and-alertness-in-the-blind-2/

Contributor Lynne Lamberg – 5-part Series: Improving Sleep and Alertness in the Blind

Part 2: How the body clock works

Non-24-hour sleep-wake disorder (N24HSWD) is a little recognized consequence of living in constant darkness.

In sighted people, daylight exposure organizes daily life. It sets the hands of the body’s master clock, a tiny pair of nerve clusters in the center of the brain that anchor body rhythms to the earth’s 24-hour light/dark cycle.

This master clock governs the alternation of sleeping and waking, body temperature, blood pressure, secretion of hormones, hunger, urination, cell division, mood, and hundreds of other physical and mental functions that occur in synchrony with the earth’s 24-hour rotation. These daily rhythms are called “circadian,” from the Latin words, “circa,” meaning about, and “dies,” a day.

Humans and most other day-active species have a circadian clock that usually runs on a slightly longer than 24-hour cycle, typically, 24 to 25 hours long. This built-in flexibility allows people to stay up late or get up early if desired, travel across time zones, live at different latitudes, and adapt to changing day length over the year.

Researchers study circadian clocks in caves and windowless research laboratories with no clocks or other indicators of time. Both sighted and blind people participating in such studies typically go to sleep and get up from a few minutes later to about an hour later day after day. Each person’s schedule is unique.

In the outside world, daylight keeps internal clocks in sighted people from drifting. Daylight synchronizes inner rhythms with the planetary light/dark cycle every day.

The eyes, and only the eyes, detect light for this purpose, Lockley said. Light signals travel from the eyes to the master clock over a special pathway that differs from the one used to send visual signals.

About 55 per cent of people who totally lack light perception, and virtually all of those with no eyes, experience N24HSWD, Lockley said. A small proportion of blind people with no conscious awareness of light perception still retain the ability to detect light, which enables circadian synchronization of their body rhythms. Visually impaired people who can detect light seldom develop N24HSWD.

In 1977, Laughton Miles and his colleagues at Stanford University published a landmark report, “Blind man living in normal society has circadian rhythms of 24.9 hours.” Despite the man’s diligent efforts to stick to a regular schedule for bedtime, rise time, work, and meals, his body rhythms continued to drift around the clock.

A person whose body clock runs on a 25-hour cycle may go to sleep an hour later each day, moving around the clock in 25 days. He or she may experience about two weeks of good sleep followed by two weeks of bad sleep, and then repeat this cycle.

Someone whose body clock runs on a 24.1 hour schedule, however, will drift only six minutes per day and take 241 days, or about eight months, to go around the clock. This person may sleep well for four months, and then badly for four months, before returning to good sleep, then bad sleep, and so on. Such individuals and their physicians may attribute the sleep disturbance to ordinary insomnia rather than to a body clock disorder. Ordinary insomnia, however, does not wax and wane with such regularity.

Humans occasionally have body rhythms that are shorter than 24 hours. These people go to sleep earlier and get up earlier each day, drifting backwards around the clock. Totally blind people who report no cyclic difficulties may have an internal clock with a period very close to 24 hours that is synchronized by time cues other than light, such as a regular schedule for sleep, work, meals, and exercise. Some people have a clock that runs on a 24-hour cycle.

Part 3 of this report will describe efforts to help people with N24HSWD stabilize their internal clocks.

Link to Introduction from the Editor: http://www.matildaziegler.com/2011/09/26/letter-from-the-editor-september-26-2011/

Link to Part 1: http://www.matildaziegler.com/2011/10/05/contributor-lynne-lamberg-5-part-series-improving-sleep-and-alertness-in-the-blind/

Contributor Lynne Lamberg – 5-part Series: Improving Sleep and Alertness in the Blind

Part 1: It’s not just insomnia

Dan Roy, who is 52 years old, and congenitally blind, has experienced recurring bouts of troubled sleep and daytime fatigue since childhood. These alternate with episodes of good sleep and alertness.

“Sometimes I fall asleep and stay asleep. Other times I wake up after a few hours and can’t get back to sleep,” he reports. “I may feel tired at different times of day, and still not be able to fall asleep at night.”

Over the years, Roy sought help from several physicians, to no avail.

“They told me, ‘You’re not sleeping right. You must be staying up too late or sleeping too late,’” recalls Roy, who lives in Des Plaines, Illinois.

A Braille translator for Horizons for the Blind, Roy said he compensates for times when he feels less productive by working harder when his energy is high. “I try to fight through my sleepiness,” he said.

“It’s like living with arthritis,” he added. “That doesn’t mean I wouldn’t like to fix it.”

Melanie Brunson, a lawyer and executive director of the American Council of the Blind in Arlington, Virginia, has been blind since birth. Born prematurely, and given oxygen, she developed retrolental fibroplasia (RLF), today called retinopathy of prematurity.

Now 57 years old, Brunson reports she recognized only 15 or 20 years ago that variations in her sleep and alertness followed a predictable pattern.

“I may be fine for several months,” she said. “Then I will have trouble falling asleep and staying asleep again.” Daytime sleepiness occasionally proves overwhelming. Fortunately, she said, she can tell her assistant, “I’m closing the door to my office for 30 minutes. I have to take a nap.”

Some members of the blind community send email at 3:30 a.m. and joke about insomnia, Brunson said. Many avoid complaining about daytime fatigue, however. They don’t want to imply that they fall asleep on the job.

Roy and Brunson both found their way to Boston’s Brigham and Women’s Hospital, and to Harvard Medical School neuroscientist Steven Lockley. Lockley has been studying disturbances of the sleep/wake cycle in blind people for the past 15 years, first in England, and more recently, in the US.

The symptoms Roy and Brunson experience characterize what sleep specialists call non-24-hour sleep-wake disorder (N24HSWD). This disorder occurs far more often in people who are blind than in those who are sighted. An estimated 50 000 to 100 000 blind individuals in the US, and140 000 in Europe, have N24HSWD.

Lockley heads a multi-center clinical trial to determine if a new medication is both safe and effective in helping totally blind people obtain regular and sufficient sleep at their preferred sleep time.

The researchers are seeking study participants. More information is available at http://24sleepwake.com/, or at http://clinicaltrials.gov/ by searching on “N24HSWD.”

Part 2 of this report will discuss how the body clock works and why blind people experience N24HSWD.

Link to Introduction from the Editor: http://www.matildaziegler.com/2011/09/26/letter-from-the-editor-september-26-2011/

Letter from the Editor – September 26, 2011

Hello Everyone,

As always, I hope you all had a nice weekend.

We’ve got a great magazine lined up for you all this week and I hope you all enjoy it. Also, I’m still in the process of putting together a comprehensive events supplement for Fall and Winter 2011, so please feel free to continue sending in suggestions. The more the merrier.

I also want to let you all know about a series of articles that will be coming up in October. I was contacted a little while ago by a research institute that is investigating Non-24-Hour Sleep-Wake Disorder, something that occurs almost exclusively in people who are totally blind. This disorder results in recurring bouts of trouble falling asleep and staying awake. Since our magazine reaches many blind and visually impaired individuals throughout the United States and the rest of the world, they felt that we would be a good medium to get the word out about the study they’re doing. The articles will also serve as an opportunity to bring this issue out into the open and possibly clear up and misconceptions or questions you all may have.

The series will be made up of five parts, beginning next week with an introduction that will outline what Non-24-Hour Sleep-Wake Disorder is, and will include various interviews of blind individuals who live with it. The series will then outline current treatments and ongoing research that is being performed to remedy the disorder.

These articles will be written by Lynne Lamberg, co-author of The Body Clock Guide to Better Health, published in 2000. Lynne has written extensively about sleep medicines and disorders for both physicians and the general public.

If you would like to familiarize yourself with the studies being done prior to the appearance of the articles in this magazine, you can visit www.non24registry.com or call 888-389-7033. For more information on Non-24-Hour Sleep-Wake Disorder, you can visit www.24sleepwake.com

Since we have had articles published in the past, as well as Reader’s Forum discussions regarding troubles sleeping and the various remedies, I thought that this series would be interesting to all of you and may answer some questions you have. I also want to point out that we are not being paid, nor are we paying to feature this series. This series will not be an advertisement for the company performing the research. If you are interested in participating in any studies that they are doing, you are free to contact them, but the main goal of this series for me was to provide all of you with the best information possible regarding a disorder that almost exclusively affects the blind and visually impaired population.

That should cover everything for now. I hope you all have a great week.

Take care, and thanks for reading.

Sincerely,
Ross Hammond, Editor