Treatments for Non-24-Hour Sleep Wake Disorder (Non-24) are aimed at resynchronizing the patient’s internal body clock to the 24-hour day-night cycle. While appropriately timed light exposure that resets the phase (i.e., timing) of the internal body clock to the 24-hour day-night cycle is important to most people and other mammals, light exposure is only effective in the sighted. Dietary melatonin is a commonly used treatment for Non-24, although no large-scale clinical trials of melatonin therapy for Non-24 have been conducted to date.
Appropriately timed light exposure is important to non-blind humans and other mammals because it acts as the major environmental cue that resets the phase (i.e. timing) of the internal body clock to the 24-hour light-dark cycle Most sighted patients with Non-24 have a circadian rhythm period longer than 24 hours that creates a daily delay in their phase. Thus, they need to reset their rhythms with an appropriate phase advance. Under normal circumstances, morning light will cause a phase advance of the clock, and evening light will cause a phase delay. The ‘cross-over’ point, where delay responses switch to advance responses on this Phase Response Curve (PRC), occurs around the time of the core body temperature minimum, which is usually 2 to 3 hours before habitual wakeup time (typically about 5-6 am). For phase advance resetting to treat Non-24 properly, therefore, light exposure must occur after core body temperature reaches its minimum. In practice, if an individual maintains a fixed, stable light therapy time, the circadian clock should eventually reach the correct phase. Continued maintenance of a stable and regular schedule is required for continued therapeutic benefit.
In 2014, the Food and Drug Administration (FDA) approved the medication tasimelteon (found under the brand name Hetlioz) for the treatment of Non 24-Hour Sleep Wake Disorder (Non-24) in blind individuals.
Tasimelteon is a melatonin receptor agonist. It works by targeting receptors in the brain that control the timing of the sleep-wake cycle. In clinical trials, totally blind individuals with Non-24 who were treated with tasimelteon slept longer during the night. Tasimelteon was also found to decrease the amount of time totally blind individuals with Non-24 slept during the day.
The most common side effects of tasimelteon include headache, elevated liver enzymes, nightmares or unusual dreams, disturbed night’s sleep, upper respiratory or urinary tract infection, and drowsiness.
Tasimelteon should be taken as prescribed by your physician. It should be taken at the same time every night before bedtime. Because it may impair activities that require complete mental alertness, people should not plan any activities other than preparing themselves for bed after taking it.
Melatonin is a possible treatment for both blind and sighted individuals with Non-24. Melatonin is a hormone, produced by the pineal gland, and is the biochemical signal of darkness. Melatonin has a nighttime peak both in species that are active during the day and species active at night. It can be synthesized artificially and, as with light, melatonin treatment can shift the circadian clock earlier (an advance) or later (a delay) depending on the timing of administration. For those with a normal sleep-wake cycle, melatonin administration from ~1pm to 1am will cause an advance, with dosing at ~7 pm producing the maximum advance, prior to the natural melatonin rise.
Assessing the patient’s circadian phase prior to treatment is important to ensure appropriate timing of melatonin and successful results. The most important point to make about melatonin treatments is that it should be given on a strict 24-hour cycle; that is, at a fixed time each night.
Studies on the blind suggest that 0.5 mg/day is an effective dose, and research studies do suggest that it is a relatively safe drug in most patients. Since melatonin supplements sold over the counter are not rigorously tested for purity or quality, care should be taken to ensure melatonin is from a reliable source and of pharmaceutical grade. With melatonin therapy, a correct diagnosis, the initial and maintenance doses, and timing of administration must be determined while under the care of a sleep specialist.
Fatigue is a constant battle for people with Non 24-Hour Sleep Wake Disorder (Non-24). But, there are some things you can do to help fight fatigue. Here are some general tips for managing fatigue:
If you think you have Non 24-Hour Sleep Wake Disorder (Non-24) and are meeting with your doctor, it’s best to go prepared. Here are some tips to get the conversation started:
Know your symptoms, and be prepared to discuss specific questions and examples you may have. In order to keep track of the symptoms you’ve been experiencing, we’d suggest recording the hours you sleep and wake each day in a tool such as the National Sleep Foundation Sleep Diary.
Be prepared to discuss additional details of your sleep, including:
You will also want to ask specific questions of your doctor about his or her experience with Non-24. Questions you may wish to ask include:
Most physicians and Non-24-Hour Sleep Wake Disorder (Non-24) patients are unfamiliar with the circadian rhythm disorder because large-scale studies of both sighted and totally blind patients have yet to be conducted. Such studies are crucial in developing criteria for diagnosis. Without progress in research and the availability of support groups, Non-24 patients continue to suffer devastating economic and social blunders. Simply telling Non-24 patients to “try harder” will not help their condition because they have no control of their disorder.
Many Non-24 patients find it hard to obtain an accurate diagnosis because primary care and non-sleep-specialist physicians are likely to not know, or know little, about the condition. If individuals are noticing a pattern of excessive daytime sleepiness and finding it hard to maintain a normal 24-hour sleep-wake cycle, or cyclic episodes of good and bad sleep, over weeks or months at a time, it is best to contact a sleep healthcare professional as soon as possible. The doctors will likely perform both physical and hormonal circadian rhythm tests and ask for a sleep diary to be kept for several weeks or months.
Support groups and educational forums for this disorder remain scarce. The website Non-24.com provides networking opportunity for those seeking others like themselves. The website is created by a pharmaceutical company that produces and sells the only FDA-approved medication to treat Non-24. The most important thing to remember is that you’re not alone! There are many more people with Non-24 than documented, and many do not even realize they have the condition. Increasing awareness of this disorder will help create a forum where sufferers can find a place of refuge to spark conversation and find support.
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