N24 Awareness Day 2014: Myths and Reality

24 November 2014 at 02:07 | Posted in Circadian rhythm | 9 Comments
Tags: , , ,

Well, it’s that time of year again. The nip of Autumn is in the air, and that can mean only one thing, N24 Awareness Day. Just one year ago, the N24 community celebrated the first N24 Day, having designated November 24th as our day to spread awareness of the condition.

2014 has certainly been an eventful year for awareness of N24. In January of this year the US Food and Drug Administration approved the first drug specifically designated for the treatment of N24 in totally blind patients. In the US, advertising of medicines is permitted and Vanda has been running advertisements on television and radio talking about N24. A year ago the average person had never heard of N24. Now, if you were to ask someone (at least in the US) if they had heard of N24 there is a good chance the answer would be yes, because of the Vanda campaign.

But awareness does not necessarily mean understanding. Unfortunately as awareness has spread, so have a number of myths and misconceptions about N24.  People with N24 I have talked to tell me of the reactions that they now get which reflect these myths. It is worth addressing this issue.

2014 Icon

Myth #1: “N24 only happens to blind persons”.

Vanda’s Non-24 campaign has particularly talked about blind persons since that is the population for which the drug is approved. It is true that if you are blind your chance of having N24 increases dramatically. Over 50% of totally blind persons will have N24. It is a serious condition — many blind persons have even said it is the worst part about being blind.

But N24 also occurs in sighted persons. I am sighted myself, and so are many other people with N24 that I know. There are many research articles on the condition and it is agreed that it does occur in individuals who have sight.

In the case of blind persons, the cause of N24 is the absence of light as a zeitgeber to regulate the circadian clock.  This is not usually the issue with sighted persons.  In sighted N24 the cause is a more complex dis-regulation of the body’s circadian system and sleep wake cycle.  Although blind and sighted N24 share the same diagnostic name, the biology is quite different.

The rate of occurrence of N24 among sighted persons is much smaller than among the blind, but there are also many more sighted people overall. We don’t really have a good estimate of the total number of sighted N24s. We can put a lower bound. There are about 100 case reports in the medical literature. And online support groups number in the low hundreds. This is still a small percent of the population, but sighted N24 does exist.

Myth #2: “N24 is a disease invented by drug companies”

It is understandable that the average person, never having heard of this somewhat exotic condition, and suddenly deluged with paid advertising might think this condition was concocted for profit. One person with N24 told me her social services worker said, “Oh, N24, that’s that disease that no one really has.”

Nothing could be farther from the truth. Anyone who thinks that is the case needs to talk to the many persons who have suffered for years with this awful condition.

In my own case, I first developed N24 in 1982. I doubt I was influenced by a drug ad 30 years in the future. I was first diagnosed in 1992 at the National Institutes of Health. They didn’t just take my word for it. They conducted a 2 year study, with round-the-clock monitoring of blood chemicals via an IV line and a slew of other medical tests. This is a real condition due to a disorder of the biological clock and the regulation of the sleep-wake cycle.

There are many others who have endured this condition. You can read some personal accounts at the CSD-N web site under “personal stories”.

Bottom line: N24 is real and the suffering it causes is real.

Myth #3: “You can just take a pill and fix your N24”.

Again, this is an understandable reaction to a drug company campaign. But the reality is more complicated.

Let’s first deal with blind persons, the target population for the new drug Hetlioz. The most straightforward way to measure response to an N24 treatment is the percent who achieve entrainment. Entrainment does not mean everything is fixed, you can still have major symptoms such as debilitating exhaustion, but lack of entrainment does really mean treatment has not worked.

In the case of Hetlioz about 20% of patients achieved entrainment after 1 month of treatment. After 7 months this rose to to 59% although that figure does not include those who dropped out of the trial or whose period was not measured at 7 months. When all subjects are included, the percent of those who started the trial and achieved both entrainment and reduced symptoms at 1 or 7 months was only 28.9% (1). So success is by no means guaranteed and treatment can take a long time to achieve results.

This isn’t meant to single out Hetlioz for criticism. It may be a useful drug for some and I am glad it is available. Melatonin is also effective in many cases of blind N24. But neither is anything close to 100% successful for blind patients. The point is not that Hetlioz is an ineffective drug, because it does help a percentage of sufferers. The point is that N24 is hard to treat.

We don’t yet have data on Hetlioz in sighted N24s. The biology of sighted N24 suggests that melatonin and melatonin agonists such as Hetlioz may be of less use than in blind subjects. The prolonged intrinsic period of some N24s may be outside the range of entrainment by melatonin-like drugs.  In practice, while some sighted N24s respond to melatonin and related drugs, most do not (2).  Whether this will be any different with Hetlioz remains to be seen.

Of course sighted N24s have some treatment options not available to totally blind persons, namely light and dark therapy. These treatments can be successful in some cases, but not all. And the light/dark regimens are complicated and time consuming. Nor does this approach correct the underlying cause of the disorder. It is a symptomatic, not a curative treatment. Even when light entrainment works patients may be left with substantial residual symptoms such as tiredness or a split sleep schedule. I am known for strongly encouraging people to try light/dark treatment, but it is not a panacea.

All of this is a far cry from popping a pill to fix the disorder.

Those are three of the myths I have heard circulating in the past year. It has changed my perspective on how to approach N24 in discussions with medical professionals and the public. In the past when I told them I had N24 (or hypernycthemeral syndrome as it used to be called) I was greeted with a blank stare or “what is that?…can you spell it?” The reaction might be skeptical. On the other hand I was dealing with a blank slate and could tell them about the condition if they were willing to listen.

Now the situation for those of us with N24 is different. The good news is, people now may have heard of the condition. The bad news is, what they think they know about the disorder may not be the truth. In the words of Mark Twain, “It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so”

With this new awareness, are we better off or not? I’m not sure. What do you think?

–posted by LivingWithN24 (James Fadden)

This post also appears on the CSD-N web site where you can find out more about N24 and other circadian disorders.

REFERENCES:

1. Marlene Dressman PhD. Clinical Program Efficacy. Tasimelteon, as presented to the FDA Peripheral and Central Nervous System Drugs Advisory Committee November 14, 2013 Silver Spring, MD slides CE-79 and CE-81

2.Kamei Y, Hayakawa T, Urata J, Uchiyama M, Shibui K, Kim K, Kudo Y, Okawa M. Melatonin treatment for circadian rhythm sleep disorders. Psychiatry Clin Neurosci. 2000 Jun;54(3):381-2.

Advertisements

9 Comments »

RSS feed for comments on this post. TrackBack URI

  1. I accidentally stumbled on this blog and am very curious regarding what to tell physicians. I live in Denmark and had never heard of this impairement in 32 years of life. However, when I did discover it, it felt like coming home (I am sighted by the way). Now I have seen my regular doctor and she has refered me to a sleep-clinic. I am very concerned because I am afraid the will not take me seriously. Do you have any advice or sources you could recomment? I apologise in advance if I am posting this in the wrong place.

  2. […] Click here to read the whole entry […]

  3. Thank you so much, LivingWithN24, for this almost impossibly well-written and readable post! This must be the go-to article for anyone wondering about N24; I can’t imagine the condition being better explained than this.
    .
    I’ve read somewhere that Vanda’s drug ‘Hetlioz’ very recently has been FDA-approved also for sighted patients. (?) If that is the case, it will be very interesting to see if it can help any of you. I share your doubts about the usefulness of ‘Hetlioz’ for sighted people with N24, but it would be sooo delightful to be proven wrong about that.
    .
    Thanks again, L, for spending the time it took to write this. It is excellent.

  4. Welcome, Trine, and thanks for writing. Sorry to hear you have N24, but at least it is no longer so *totally* unknown. If you are on Facebook, you may want to join the friendly group “Non 24-Hour Sleep-Wake Syndrome Support Group” for contact with others.
    .
    I’ve been keeping a list of doctors recommended by people with DSPS or N24, but I have no doctor listed for Denmark (yet); please let me know if you find one! I intend to add the complete list to this blog soon; meanwhile here are the names I have that are nearest you:
    .
    Frode Engtrø, M.D. familiar with Circadian Rhythm Disorders
    Spesialist i Allmenmedisin, Idnr 8352798
    Mathesongården legesenter, NO-7011 Trondheim, Norway
    Telefon: 73 87 04 80
    .
    Fred Holsten, MD, PhD, Professor of psychiatry, sleep specialist
    Bergen søvnsenter
    Bryggen 9, NO-5003 Bergen, Norway
    http://www.bergensovnsenter.no/
    .
    Hans Wickbom, Överläkare
    Avesta, Dalarna, Sweden
    Telefon: 0226-49 61 37
    http://www.ltdalarna.se/Halso–och-sjukvard/Specialiserad-vard/Medicin/Avesta/Somnlab/
    .
    Perhaps if you contact one of these men, you might be given the name of a specialist in Denmark. You could also ask your sleep clinic to contact them, if the clinic isn’t immediately cooperative. Good luck!
    .
    (Jeg kan ikke dansk, kun norsk. Til daglig skriver jeg nynorsk, men til deg bruker jeg bokmål. Jeg har forsinket søvnfase, DSPS. N24 er relatert, men verre, som du vet. Beste ønsker til deg.)

  5. I saw an ad today on TV regarding non-24. This is the first time I have heard of this, but at last, there is a name that may explain my life-long sleep patterns. I am a 64 year old sighted female that simply does not conform to a 24 hour wake/sleep day. I no longer work and stay home, sleeping when I can which is mostly during the day but varies. By grabbing naps here and there I can usually adjust my sleep times to accomodate some social events, but even then, this eventually catches up with me. Thank you for this blog. I intend to read everything I can on here and learn more about what I might do to help live in a 24 hour world. I intend to start keeping a sleep diary, but I would guess my sleep days consist of 28 to 30 hour days with only 4 to 5 hours of sleep. My mother tells that she took me to the doctor when I was preschool age regarding the fact that I didn’t sleep very many hours but stayed awake long periods of time. Do you have any recommendations on keeping an accurate sleep diary or what I should do to determine my personal internal sleep clock? Thanks. Judy V.

  6. Hi Judy, I am glad you have finally found out the explanation of your sleep problems. With regard to keeping a sleep log or chart, you may want to look at my post on Charting the Course of N24, also on this blog.

    https://delayed2sleep.wordpress.com/2010/10/27/60-charting-the-course-of-n24/

    What you said about your childhood is interesting. I was the first child in my family so my mother did not know what to expect. But my grandmother had raised many children and told her “there is something wrong with this child. He doesn’t sleep.” My mother also took me to a pediatrician who offered to prescribe phenobarbital (a powerful sleeping pill). Luckily my mom did not take up the offer. The doctor said I would be glad later in life that I didn’t need to sleep much. It didn’t quite turn out that way.

  7. to livingwith24 – thank you for your response. I have read the post you mentioned above and plan to start logging my sleep patterns as you indicated. I am just so glad to learn that I am not alone with such irregular sleep patterns and requirements. Just finding something that even begins to explain this makes me want to cry. Thank you so much for this information.

  8. In part because of your site, I believe I have N-24. Since I was a teenager I’ve had trouble sleeping during the night. I’ve always had a sleep schedule, since then, that was very delayed and also tended to become later each night. My life became a battle against staying up late and sleeping in. I always felt anxious knowing that I couldn’t regulate my sleep to be like other people’s. In the last couple of weeks, I have allowed myself to sleep when I wanted/needed to. My sleep schedule advanced around the clock and it looks like it will come back to where it was before after about 1 more week (3 weeks total), which would make my sleep cycle about 25 hours long. I have noticed for many years that my sleep cycle appeared to be more than 24 hours.

    I am a freelancer and artist, so I have the ability to follow my own sleep schedule. The question is, is that harmful in itself? I don’t feel any worse and I actually feel better now. I feel like treatment would be a big battle every day against what my body naturally wants to do.

    Thanks for your reply.

  9. That is a very interesting question and the answer is complicated. (I apologize fro the delay in responding — it’s been a tiring week.)

    Forcing yourself to stay on a 24 hour schedule is very stressful, especially if it results in constant sleep deprivation. That can’t be good in the long run.

    On the other hand free-running may also have some negative effects. I had a number of hormonal studies done and they showed that when I am free-running the production of a number of hormones is affected. The most dramatic is melatonin – I produce no melatonin when free running. Other hormones are also affected, for example my cortisol rhythm when free-running is very irregular. I also have disturbances in TSH and other hormones.

    When I am entrained with light and dark therapy, some but not all of these abnormalities are corrected. My melatonin and cortisol rhythms become normal. Other abnormalities such as TSH continue to be present.

    So there are problems both with following your own schedule and with trying to stay on 24 hours. It’s a matter of deciding which is worse, so there is no easy answer.

    I would say this: If it is a matter of just forcing yourself to be on a 24 hour schedule I think the stress of that is so difficult it is best to follow your own schedule.

    On the other hand if you are able to use light and dark treatments (or perhaps melatonin) to make staying on a 24 hour schedule tolerable (but perhaps still difficult), that would be worth considering. The aim of such treatments is to make one able to entrain without extreme effort or stress. But the degree to which that aim is achieved is variable. The treatments are not effective for everyone and even in the best cases don’t eliminate symptoms entirely.

    I myself try to entrain when I can (so I can make appointments etc.) using light/dark therapy, but it does not always work and sometimes I have to revert to free-running.


Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

Blog at WordPress.com.
Entries and comments feeds.

%d bloggers like this: