Tasimelteon The Food and Drug Administration (FDA) approved in January 2014 the melatonin agonist tasimelteon for the treatment of<unk> -24 for blind people. This is the first FDA-approved drug for any circadian rhythm sleep disorder, since melatonin is unregulated. In the largest treatment study with<unk> -24 patients, it was demonstrated that tasimelteon safely and effectively treated totally blind patients: entrainment occurred in 20% (8 of 40) of patients receiving the drug compared with 3% (1 of 38) receiving placebo. In a separate meta-analysis, melatonin supplementation achieved a 67% (12 of 18) entrainment rate. Studies directly comparing tasimelteon and melatonin have yet to be performed. Study authors noted that the lower rates of entrainment with tasimelteon may have been due to short duration of treatment. Melatonin, light therapy and dark therapy Phase response curves for light and for melatonin administration Melatonin administration 1<unk>  before bedtime is considered another treatment for those suffering from<unk> -24. However, it is important to note that melatonin may only treat the inability to sleep and may not help to improve the daytime sleepiness. Light therapy, which involves a bright light exposure of thousands of lux of white light or about 400 lux of blue light on awakening to counteract the tendency for circadian rhythms to delay (similar to treatment for delayed sleep phase disorder and seasonal affective disorder), is not currently recommended until more studies appear, although it has been found to be effective in some cases. This can be combined with dark therapy (or scototherapy), which involves filtering blue light (using software, screen filters or (amber-color) glasses) and preferring red-colored lights with a low amount of lux in the few<unk> s before bedtime to avoid melatonin suppression. Both melatonin administration and light therapy work by shifting circadian rhythms according to a phase response curve (PRC), with the melatonin PRC being essentially the inverse of the light PRC. Furthermore, light can suppress melatonin secretion. Both have a duration of approximately 12<unk> s, in opposite phase: light PRC spikes at the beginning of the day and lowers throughout the day with a depression after 8<unk> s for the last 4<unk> s, whereas natural melatonin spikes at the start of the biological night and drops around the time of waking up or light perception. The first 8<unk> s are called the "advance zone" whereas the last few<unk> s the "delay zone". The change from advancement to delay zones is progressive, passing through a long area of no effect (a "dead zone"), but the change from delay to advancement is abrupt, occurring a few<unk> s before wake-up time or bedtime for light or melatonin respectively. When melatonin supplementation is taken in the melatonin PRC advance zone (i.e., the last few<unk> s before bedtime), it resets the clock earlier; when taken in the melatonin PRC delay zone (i.e., few<unk> s before and after wake-up time), it shifts the clock later. In other words, melatonin has most effect when it is taken at times when natural melatonin is not normally present, thus during the day: when taken in the morning, melatonin causes phase delays (shifts to a later time), and when taken in the afternoon/evening it causes phase advances (shifts to an earlier time). However, for a sleep phase delayed person, the time of biological morning and biological afternoon/evening might differ depending on the circadian clock shift in the affected person. This means that if melatonin is taken during the usual bedtime and wake-up time (i.e., usual nighttime), it may have no effect. Therefore, successful entrainment depends on both the melatonin dosage and the appropriate timing of melatonin administration. The accuracy needed for successfully timing the administration of melatonin might require a period of trial and error, as does the dosage. However, entrainment was also observed when giving a dose of melatonin as low as 0.05 mg and without any timing, by just continuing melatonin administration at the same time every day until the<unk> -24 sufferer's circadian rhythm shifted enough to coincide with melatonin administration (which took from 1 to 2 months). In addition to natural fluctuations within the circadian rhythm, seasonal changes including temperature,<unk> s of daylight, light intensity and diet are likely to affect the efficacy of melatonin and light therapies since these exogenous zeitgebers would compete for hormonal homeostasis. Further to this, there are unforeseen disruptions to contend with even when a stabilized cycle is achieved, such as travel, exercise, stress, alcohol, or even the use of light-emitting technology close to a subjective evening/night.
Non-24-hour sleep–wake disorder
Circadian rhythm sleep disorder
Delayed sleep phase disorder
Irregular sleep–wake rhythm
Advanced sleep phase disorder
Shift work sleep disorder
Excessive daytime sleepiness
Sleep state misperception