How Can Melatonin Be Used to Help Sleep?

Patient Presentation
A 20-year-old male came to clinic because of several nights of insomnia. He had several nights where he suddenly significantly changed the time he normally went to sleep, and then for the next 5 evenings when he could restart his normal bedtime, he had a hard time being able to initiate sleep. “I just sit there with my eyes wide awake and just can’t fall asleep,” he said. “I finally get to sleep about 4 hours later and then I can’t get up in the morning. When I do wake up I’m too scared to drive to my college classes,” he related. He denied any depression or anxiety. He said he had normal stress about his classes but was doing well. He was studying software engineering and therefore was often using electronic devices up until the time he went to bed. He denied any medications or drug use. He said that sometimes eating some food would help him fall asleep but a bigger meal made it worse. The past medical history showed a healthy male, who had previous episodes of a similar sleep problem that generally stopped after 1-2 nights. The family history showed some diabetes, and occasional insomnia in the father. There was no history of mental health problems. The review of systems was normal.

The pertinent physical exam showed a healthy male with normal vital signs and physical examination. The diagnosis of a short term sleep-onset problem was made. The patient was counseled to improve his sleep hygiene with careful attention to his schedule and also the amount of screen use he had. “Because you are using computers for school and will be for work, you are going to have to be very aware of the amount of the use, and the timing of the use, as you seem to be more prone to this sleep problem. Having a bedtime routine where you can stop the computers, maybe read or listen to music for a little while in a chair or couch and then go to your bed will probably help,” the pediatrician counseled. “Your bed should be for sleeping and not for other things like coding and homework. You can also try drinking something warm, making sure there is low-lighting in the room,” he added. “Since you are already having a problem you can also try some melatonin for a few days as a sleep aid. You should take it 2 hours before you want to fall asleep and you can do it for about a week if you need to. If it is not working call me. If this happens again, try restarting your schedule and sleep practices, and if needed you can try the melatonin again,” he said.

Discussion
Sleep is regulated by the homeostatic sleep drive and the circadian system which controls periods of activity and inactivity throughout the day. The circadian rhythm is slightly longer than 24 hours in humans and is controlled by the hypothalmic suprachiasmatic nucleus. When the circadian system and the external environment are misaligned, such that sleep occurs outside of normal times, a circadian rhythm sleep disorder can occur.

Everyone experiences disturbances of sleep throughout their lifetime. During adolescence, there is a normal physiologic change so that there is a shift to a later sleep phase for adolescents. Adolescents also commonly have inadequate sleep that occurs on an ongoing basis because of societal norms of having to awaken early in the morning. Pediatric insomnia is defined as “repeated difficulty in sleep initiation, duration, consolation, or quality that occurs despite age-appropriate time and opportunity for sleep and results in daytime functional impairment for the child and/or family.” Mild or transient problems are not a sleep disorder or insomnia. The problem must be more consistent, and be developmentally inappropriate.

Adolescents and young adults can have circadian rhythm problems occur.

Delayed sleep phase disorder (DSPD) is the most common in this group with a the prevalence of 7-16%. DSPD delays sleep onset by 3 to 4 hours compared to usual normative evening time (i.e. 10-11 PM). If left alone, the sleep is normal in quality and duration. Sleep wakening is then necessarily delayed causing problems with social needs (e.g. not getting up in time to go to school). The adolescent then has inadequate sleep which then leads to poor sleep hygiene which helps to change the intrinsic circadian rhythm which continues to cause the delayed sleep onset. Overtime, DSPD develops. DSPD is treated using good sleep hygiene but other interventions may be necessary.

  • Chronotherapy delays sleep onset progressively over several days until the normal sleep onset time is achieved and then anchors that new time with post-sleep morning light.
    Light therapy especially in the morning can be helpful.

  • Light in the evening delays sleep onset and light in the morning advances it (i.e. makes it earlier in the evening the next night). Light intensity between 2500-10000 lux will advance circadian rhythms.
  • Melatonin can also be used.

Sleep hygiene including establishing regular sleep routines and timing that can be consistently adhered to (both for sleep onset and duration), limiting technology devices especially those with a blue screen such as television and computers, limiting caffeine and energy-dense food before bedtime, regular exercise during the day and not in the evening and treatment for any underlying problems such as depression or anxiety.

Psychophysiologic insomnia (PPI) is a sleep-onset disorder and is not a circadian rhythm sleep disorder. Individuals have a very hard time initiating sleep and then difficulty in wakening in the morning. PPI and DSPD can be concurrent.

To learn more about circadian rhythms in newborns click here and a review of sleep hygiene for infants can be found here.

Learning Point
Melatonin is an indolamine that is made in the pineal gland and has chronobiotic and hypnotic properties. It also has anti-inflammatory, antioxidant and free radical scavenging abilities. Circulating endogeneous levels are high in childhood and decrease during puberty. It is metabolized by the liver and has a half-life of 45-60 minutes. Medications such as oral contraceptives and cimetidine decrease melatonin metabolism and carbamazepine and ompeprazole can increase melatonin metabolism. In humans endogenous melatonin starts to rise about 2 hours before sleep onset and peaks about 5 hours after sleep onset.

It can be used to help re-entrain short-term or long-term circadian rhythm problems or be used to help prevent sleep disruption following environment insults. It has also been used to treat headaches and seizures.

  • For PPI, melatonin is taken 2 hours before desired sleep onset as a soporific (weak sleep aid). Dosages vary but 0.2-0.5 mg can be used as a starting point.
  • For DSPD, melatonin is taken 5 hours before desired sleep onset to help retrain the system. Dosages vary but small doses have been found to be as effective. For children a 0.2-0.5 starting dose or 0.5- 1 mg in adults, which can be increased by 0.2-0.5 mg weekly until desired effect with a maximum of 3 mg in children/teens 40 kg is one regimen. Once a consistent, desired bedtime is achieved, smaller dose (such as 0.2-0.5 mg) given 2 hours before desired sleep onset helps to establish the circadian pattern.
  • For jet lag in adults 3 mg is often prescribed.
  • In children with long-term insomnia such as those with neurological disease can benefit. Melatonin should be re-evaluated at not less than 1 month after starting to determine effectiveness. Melatonin treatment is recommended to be stopped for at least 1 week yearly to again evaluate need for ongoing treatment.
    Long-term therapy can be stopped just before or after puberty.

Melatonin is considered safe but side effects can include drowsiness, headache, hypothermia, dizziness, diarrhea, enuresis, and rash.

Questions for Further Discussion
1. What health problems are associated with inadequate sleep? For a review click here.
2. What sleep hygiene recommendations do you offer families?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Sleep Disorders

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Bartlett DJ, Biggs SN, Armstrong SM. Circadian rhythm disorders among adolescents: assessment and treatment options. Med J Aust. 2013 Oct 21;199(8):S16-20.

Reiter J, Rosen D. The diagnosis and management of common sleep disorders in adolescents. Curr Opin Pediatr. 2014 Aug;26(4):407-12.

Meltzer LJ, Mindell JA. Systematic review and meta-analysis of behavioral interventions for pediatric insomnia. J Pediatr Psychol. 2014 Sep;39(8):932-48.

Bruni 0, Alonso-Alconada D, et.al. Current role of melatonin in pediatric neurology: clinical recommendations. Eur J Paediatr Neurol. 2015 Mar;19(2):122-33.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital