page_title: Non-24-hour sleep–wake disorder
section_title: Melatonin, light therapy and dark therapy
hierarchical_section_title: Non-24-hour sleep–wake disorder / Treatment / Melatonin, light therapy and dark therapy
caption_attribution_description: graph of a Phase Response Curve
context_page_description: Non-24-hour sleep–wake disorder is one of several chronic circadian rhythm sleep disorders. It is defined as a "chronic steady pattern comprising [...] daily delays in sleep onset and wake times in an individual living in a society". Symptoms result when the non-entrained endogenous circadian rhythm drifts out of alignment with the light–dark cycle in nature. Although this sleep disorder is more common in blind people, affecting up to 70% of the totally blind, it can also affect sighted people. Non-24 may also be comorbid with bipolar disorder, depression, and traumatic brain injury. The American Academy of Sleep Medicine has provided CRSD guidelines since 2007 with the latest update released in 2015.
context_section_description: Melatonin administration 1 hour before bedtime is considered another treatment for those suffering from non-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 hours 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 hours, in opposite phase: light PRC spikes at the beginning of the day and lowers throughout the day with a depression after 8 hours for the last 4 hours, 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 hours are called the "advance zone" whereas the last few hours 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 hours 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 hours before bedtime), it resets the clock earlier; when taken in the melatonin PRC delay zone (i.e., few hours 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 everyday until the non-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, hours 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.
caption: Phase response curves for light and for melatonin administration
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