Treatments for Non-24 Hour Sleep Wake Disorder (N24HSWD) 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 N24HSWS, although no large-scale clinical trials of melatonin therapy for N24HSWS 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 N24HSWS 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 N24HSWS 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.
Melatonin is a possible treatment for both blind and sighted individuals with N24HSWD. 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.
Will I be fully cured of my Non-24 Hour Sleep Wake Disorder?
Unfortunately, there is no permanent cure for N24HSWD. There are a number of clinical research trials being conducted to investigate the safety and efficacy of new treatments, however. The drug tasimelteon, a melatonin agonist, is currently under clinical trials to assess its ability to reset non-24-hour rhythms in totally blind patients with N24HSWS.