ADxS.org Logo
ADxS.org Logo
Search Donations Recent changes ADHD forum Deutsche Version
Register

Already have an account? Login

Header Image
Melatonin for ADHD

Melatonin for ADHD

Previous page Next page

Melatonin is a hormone. It is produced by the pineal gland from tryptophan via several intermediate steps. The onset of darkness (the loss of melatonin-inhibiting brightness) is registered via the retina and stimulates melatonin production via the suprachiasmatic nucleus in the hypothalamus. Melatonin regulates the circadian rhythm. Blind people often have sleep problems and benefit from melatonin supplementation.1 In Germany, immediate release melatonin is freely available up to a dose of 1 mg.2 In the USA, melatonin is freely available as a dietary supplement. In other countries, such as Australia and Scandinavia, melatonin is only available on prescription.

Melatonin appears to be an effective, tolerable and safe treatment for comorbid sleep disorders in both adults and children with ADHD. We are not aware of any reports of inappropriate side effects.

Problems falling asleep and staying asleep occur in 15 % to 25 % of all children and adolescents and in 25 % to 50 % of those with ADHD. Several studies and reviews show the benefits of melatonin for sleep disorders, especially in children and adolescents with ADHD, ASD or other neuropsychiatric disorders, with minimal side effects.3 There is limited data on the safety and efficacy of long-term use of melatonin.45 Others report 75% circadian disorders in children and adults with ADHD.6
A systematic review of 62 studies totaling 4,462 ADHD subjects found consistent evidence that ADHD is associated with an evening/late chronotype and phase delay of circadian phase markers such as weak melatonin onset at dusk and delayed sleep onset. There was evidence that melatonin is an effective treatment for sleep problems in ADHD. A small number of genetic association studies reported links between polymorphisms in circadian clock genes and ADHD symptoms. Overall, there was consistent evidence of a disorder of the circadian rhythm in ADHD7
Several other meta-analyses and reviews on sleep problems in children and adults with ADHD also confirmed that melatonin can shorten the time it takes to fall asleep and improve sleep quality without any significant side effects.891011

For ADHD-related sleep problems, immediate release melatonin between 0.5 and 3 mg is recommended (plasma half-life approx. 20-50 minutes, duration of action 3-4 h), which should be taken at least approx. 1 hour before bedtime and not after midnight.12
If you have problems sleeping through the night (more typical in older adults), sustained release melatonin may be useful.

1. Melatonin against sleep disorders

1.1. Melatonin for sleep disorders in children and adolescents

1.1.1. Melatonin for sleep disorders in children and adolescents with ADHD

According to various studies, melatonin is also effective for sleep problems in children with ADHD,1314 15 16 17 while melatonin has no direct effect on the ADHD symptoms themselves.18
In a study of 74 children and adolescents with ADHD (mean 11.6 years) receiving MPH, 60.8% showed a large or very large improvement in sleep behavior on melatonin treatment (mean dose 1.85 mg/day).19 One small study found improved sleep onset behavior, fewer sleep throughs and more sleep with melatonin in a group of children with mental disorders, including ADHD. There were no serious side effects.20

A systematic review on the treatment of sleep problems in ADHD in children and adolescents found a positive effect of melatonin on falling asleep, sleep duration and sleep quality. Clonidine also improved insomnia (which is why we suspect the same for guanfacine), while zolpidem and L-theanine barely showed any improvement.21

A meta-analysis on the use of melatonin for the treatment of sleep problems in children with ADHD reports that melatonin is often prescribed as an adjunctive pharmacotherapy when optimization of stimulant adjustment, sleep hygiene and behavioral therapy have not been sufficient. Melatonin regulates sleep disorders in the circadian rhythm, such as difficulty falling asleep in children with ADHD. Four studies in children aged 6 to 14 years with ADHD and insomnia showed an improvement in sleep onset and sleep latency. Adverse events were transient and mild in all studies.22 Another meta-analysis also found a significant improvement in sleep duration and sleep onset latency in children with ADHD or ASD compared to placebo, with a high response rate. Melatonin was well tolerated in the dose range of 2 to 10 mg/day in children and adolescents in both short and long application tests with few side effects.23 Further reviews support these results.2425
A meta-analysis found that melatonin brought forward the time it took to fall asleep by 40 minutes and reduced the time it took to fall asleep by 24 minutes in children and adults with sleep onset disorders.9

A cohort study from Sweden showed that in 2017, around 2% of all children aged 0 to 17 had been prescribed melatonin at least once. Overall, melatonin prescriptions increased 15-fold for girls and 20-fold for boys between 2006 and 2017. 15% of girls and 17% of boys who were prescribed melatonin for the first time between the ages of 5 and 9 in 2009 continued to be prescribed melatonin for the following 8 years. Half of the children prescribed melatonin had at least one mental Disorder. The most common mental disorder was ADHD, in all age groups and in both sexes.26
This is in line with another Swedish cohort study, according to which 40% of girls and 50% of boys aged 5 to 9 years who regularly received melatonin in 2010 continued to receive melatonin regularly after 3 years. Among 15 to 19-year-olds, only around 10% were still regular users 3 years later. In 2013, 65% of boys and 49% of girls who were regular melatonin users were also regular users of ADHD medication. The daily dosage of melatonin appeared to have decreased by almost 30% between 2006 and 2012.27
A Norwegian cohort study also shows a continuous increase in the use of melatonin (off-label in Norway), whereby mainly sleep problems that occurred comorbidly with other disorders were treated. A large number of children continued treatment for 3 years with daily dosing. The annual average dosage in the third year was 2.95 mg (1.60 to 4.93 mg) / day for boys and 2.47 mg (1.10 to 4.44 mg) per day for girls.28
A very large cohort study of 48,296 people with ADHD between the ages of 0 and 17 from 2008 to 2012 found that 30% of them received other medications in addition to ADHD medications, with melatonin being the most commonly given other medication, ahead of antidepressants and antipsychotics.29

In view of these dimensions, it is difficult to imagine that melatonin would have been used without corresponding benefits or that serious side effects of melatonin would not have been noticed.

In a Canadian survey, melatonin was the most commonly used medication by doctors for sleep disorders in children (73%), regardless of co-existing ADHD.30

A Japanese survey showed that almost half of the children with difficulty falling asleep were treated with melatonin (n = 220). The following study showed effective doses between 0.2 and 8 mg, depending on age (n = 254).31

1.1.2. Melatonin for sleep disorders in children and adolescents with autism

Doses of 1-4 mg 30-60 minutes before bedtime significantly improved sleep onset latency.3233

1.2. Melatonin for sleep disorders in adults with ADHD

1.2.1. Melatonin for sleep disorders in adults with ADHD

In a review of 41 studies, an international group of experts concluded that sustained release melatonin (2 - 10 mg, 1 - 2 hours before bedtime) in adults with insomnia symptoms or comorbid insomnia in affective disorders, schizophrenia, Autism spectrum disorders, neurocognitive disorders or during the discontinuation of sedative-hypnotics, while in adults with disorders associated with circadian sleep problems (such as ADHD), immediate release melatonin (1 mg and less) is more useful.34

A French expert commission found melatonin to be a helpful medication for adults with sleep disorders and comorbid mental disorders such as ADHD35
A meta-analysis found that melatonin in children and adults with difficulty falling asleep brought forward the time taken to fall asleep by 40 minutes and reduced the time taken to fall asleep by 24 minutes. (METASTUDY, k = 9)36

1.2.2. Melatonin for sleep disorders in older adults with primary insomnia

In older adults (55 years and older), 2 mg sustained release melatonin shows better effects, especially on sleep efficiency, than immediate release melatonin.37

2. Dose and timing of melatonin intake

Depending on when melatonin is taken, it has different effects.
Taking 2 to 4 mg immediately to (ideally) 3 hours before sleep onset shortens the time it takes to fall asleep and improves sleep quality without affecting the circadian rhythm.
Taking it 7 hours before the onset of sleep (lower doses here) shifts the circadian rhythm forward, thereby also improving the latency to fall asleep and the quality of sleep. There are also indications that this could reduce existing ADHD symptoms.

Glossary:

  • Sleep latency (SOL):
    • Time from going to bed / lights out to the first onset of sleep. Measured in minutes. Less is better.
      Wake after sleep onset (WASO): Sum of all waking phases after first falling asleep until final awakening in the morning. Measures sleep continuity / ability to sleep through the night. Lower is better.
  • Sleep efficiency (SE):
    • Percentage of time spent in bed actually sleeping. Values ≥ 85% are conventionally considered normal. Higher is better,
      Calculation of sleep efficiency (SE) = Total Sleep Time (TST) / Time in Bed (TIB) × 100 %
  • Total sleep time (TST):
    • Total time slept in minutes. Higher is better.
  • Sleep quality (SQ):
    • Definition depends on the study. Sleep quality can be a subjectively reported value, standardized e.g. via Pittsburgh Sleep Quality Index (PSQI), sleep diary or Insomnia Severity Index (ISI), or a value measured by actigraphy / PSG, which can take several parameters into account: SE, WASO, number of awakenings, sleep architecture (% N3, % REM), sleep fragmentation index, SOL if applicable.

2.1. Melatonin (up to) 3 hours before sleep: improves sleep (falling asleep)

While unretarded melatonin taken 7 hours before or several hours after bedtime shifts the circadian melatonergic rhythm forward or backward, unretarded or sustained-release melatonin taken immediately before sleep has little effect on the DLMO.

Melatonin reached its maximum efficacy in children at a dose between 2 and 4 mg/day, 3 hours before bedtime. This correlated (meta-analysis, k = 21)38

  • a reduction in the time it takes to fall asleep with an early intake in relation to bedtime
  • an increase in sleep efficiency and total sleep time with a longer treatment duration

In adults, doses of 3 (to 5) mg 3 hours before sleep onset were optimal to reduce sleep onset latency and increase sleep duration. In contrast, most studies used 2 mg melatonin 30 minutes before bedtime. (Meta-analysis, k = 26 RCT, n = 1,689)39 Studies with a dose of more than 3.5 hours before sleep onset were not included in the meta-analysis. Up to a dose of 3 to 5 mg, the pooled sleep onset latency decreased, above which it slowly increased again. Interestingly, a dose of 1 mg was even associated with worsened results. In patients with insomnia, melatonin was less effective than in healthy controls, and the efficacy of melatonin gradually increased as the time of administration was brought forward in relation to the sleep phase.

Melatonin for direct sleep promotion: 45 studies + 1 meta-analysis on intake max. 2 hours before sleep onset

Target group Dose Intake (in min / h) before bedtime Number of subjects Improvement in sleep onset latency (SOL) Improvement in sleep duration (TST) Improvement in sleep quality (SQ) / sleep efficiency (SE) Study
_________________ _________ ___________ ___________ ___________
ADHD: Children and adolescents with sleep problems
Children with ADHD, 6-14 y. on stimulants (non-responders to sleep hygiene) 5 mg immediate release 20 min before bedtime n = 27 60 min faster with sleep hygiene + melatonin unknown improved, ADHD symptoms unchanged Weiss et al., 200640
Children with ADHD under MPH 1 mg/kg, 7-12 y. 3 or 6 mg melatonin immediate release or placebo 30 min before bedtime, 8 weeks N = 50 Sleep onset significantly earlier; bedtime resistance reduced significantly increased Sleep quality improved; ADHD symptoms unchanged Mohammadi et al., 201241
Children with ADHD and MPH-induced insomnia, 9.5 to 14 years Mean dose 1.85 mg immediate release (titrated in 0.5 mg increments, 1 to 2.7 mg) 60-120 min before bedtime, ≥ 4 weeks n = 74 significantly reduced unknown CGI-I mostly much or very much improved Masi et al., 201942
Children with ADHD and high SOL (mean 135 min) unknown before bedtime n = 24 SOL over 1 hour shorter unknown Tjon Pian Gi et al, 200243
Children with ADHD-C on MPH, 7 - 12 years 3 to 6 mg melatonin by weight vs. placebo N = 50, n = 26 SOL shorter (18 min vs. 23.2 min) Sleep duration + 51 min Sleep through reduced Length growth and weight gain improved, appetite correlated with sleep duration, independent of melatonin Mostafavi et al, 201244
Sleep Phase Delay Syndrome (DSPD)
DSPS with delayed melatonin rhythm compared to bedtime 0.5 mg immediate release 1 hour n = 116 -34 min earlier (95% CI: -60 to -8) unknown Sleep efficiency increased; PROMIS scores improved Sletten et al. 201845
Children and young people with autism
Target group Dose Intake before sleep Number of subjects Sleep onset latency Sleep duration Sleep quality / sleep efficiency Study
Children with ASA 1 mg Before bedtime n = 65 -22.0 min (p0.0001 vs. placebo -5.0 min) unknown unknown Hayashi et al. 202232
Children with ASA 4 mg Before bedtime n = 65 -28.0 min (p0.0001 vs. placebo -5.0 min) unknown unknown Hayashi et al. 202232
Children with ASA, 4-10 years 3 mg sustained release (1 mg immediately, 2 mg within 6 hours) 21:00 n = 32, N = 64 Actigraphy: -34.39 min; CSHQ-SOD: -0.83 unknown unknown Cortesi et al., 201246
Children and adolescents with ASA, 2-17.5 years of age 2-5 mg sustained release, on-titration 30-60 minutes n = 125 -25.3 min (95% CI: -44.7 to -5.9) unknown unknown Gringras et al, 201747
Children and adolescents with ASA, 3-16 years 2 mg to max. 10 mg immediate release, titrated to “good results” 30-40 min N = 17 -46.7 min +52 min nocturnal awakening unchanged Wright et al, 201148
Children with ASA, medium 5 yrs. 5 mg immediate release 20 min, 4 weeks crossover n = 7 Sleep latency reduced from 2.6 hrs to 1.06 hrs Extended from 8.05 to 9.84 hours Nocturnal awakenings reduced to 30% Garstang & Wallis 200649
Children with ASA, fragile X syndrome or both, 2-15 yrs, mean 5.5 yrs 3 mg immediate release 30 min before bedtime, 2 weeks crossover n = 12 28 min faster, 42 min earlier 21 min longer Wirojanan et al., 200950
Children with ASA, 3-10 yrs 1 (bn = 7), 3 (n = 14), 6 (n = 3) mg immediate release (dose titration) 30 min before bedtime, 14 weeks open-label after 2 weeks placebo run-in n = 24 16 min faster 15 min longer Improvement in sleep, behavior and parent stress scales Malow et al, 201251
Children with ASA and Asperger syndrome, 6-17 yrs (open-label, no RCT) 3 mg immediate release in the evening before bedtime, 14 days n = 15 18 min faster unchanged Behavioral measures significantly improved (effect disappeared after discontinuation) Paavonen et al., 200352
Children with neurodevelopmental disabilities incl. ASD and DSPS, 2-18 yrs. 5 mg sustained release (CR) in the evening before bedtime, 10 days crossover, then 3 mo open-label n = 50 34 min shorter 30 min longer Clinical and global function improved; family stress reduced Wasdell et al., 200853
Children with neurodevelopmental disorders (~60 of them with ASD), 3-15 yrs (MENDS study) 0.5 / 2 / 6 / 12 mg immediate release (titrated) 45 min before bedtime, 12 weeks n = 146 58.3 min shorter (actigraph) 15.7 min longer 7.3 % fewer nights with unsatisfactory sleep Gringras et al., 2012 (MENDS)54
Children and adolescents with other disorders
Target group Dose Intake before bedtime Number of subjects Sleep onset latency Sleep duration Sleep quality / sleep efficiency Study
Children with Rett syndrome, 10 y. 2.5-7.5 mg immediate release in the evening before bedtime, 4 weeks crossover n = 9 19 min faster (p < 0.05) TST +22 min (n.s.) Wake-up unchanged McArthur & Budden, 199855
Children with Angelman syndrome with chronic insomnia, 2-15 yrs. 2.5-5 mg immediate release 30 min before bedtime, 4 weeks crossover n = 8 32 min faster (p < 0.001) 56 min longer (p = 0.001) Waking up significantly reduced Braam et al., 200856
Children and adolescents with chronic (idiopathic) sleep disorders
Target group Dose Time before sleep Number of subjects Sleep onset latency Sleep duration Sleep quality / sleep efficiency Study
Children with idiopathic CSOI, 6-12 yrs. 5 mg immediate release 19:00 (~ 2-3 hrs before bedtime) n = 62 17 min (latency) / 57 min faster (onset) (p < 0.001) 33 min longer RAND-GHRI / FS-II Health & sleep status significantly improved Smits et al., 200357
Adults aged 45 and over
Target group Dose Intake before sleep Number of subjects Sleep onset latency Sleep duration Sleep quality / sleep efficiency Study
Primary insomnia aged 45 to 60 years 3 mg immediate release 1 hour n = 51 (melatonin group), N = 97 (total) No significant improvement -30.63 min earlier wake time (p=0.001) PSQI unchanged Xu et al. 202058
Adults with insomnia aged 51 and over 0.1 mg 30 minutes n = 15 not significant Improvement reported Sleep efficiency: 84% (vs. 78% placebo) Zhdanova et al. 200159
Adults with insomnia aged 51 and over 0.3 mg 30 minutes n = 15 not significant Improvement reported Sleep efficiency: 88% (vs. 78% placebo, p0.0001) Zhdanova et al. 200159
Adults with insomnia aged 51 and over 3 mg 30 minutes n = 15 not significant Improvement reported Sleep efficiency: 84% (vs. 78% placebo) Zhdanova et al. 200159
Adults aged 55 and over 2 mg sustained release unknown n = 170 Patient reports, variable +2.2 min vs. placebo Improvement in sleep quality Lemoine et al, 200760
Adults aged 55 and over 2 mg sustained release 2 hours before sleep onset, after eating n = 40 6.9 min / 10.6 min faster vs. placebo unknown Luthringer et al, 200961
Adults 55 to 80 years 2 mg sustained release 2 hours before sleep onset N = 354, n = 171 24.3 min (3 weeks, 65-80 years); 25.9 min faster (19 weeks, 65-80 years) unknown Improvement in sleep quality Wade et al, 200762
Adults aged 55 and over (average 64.2 years) 0.3 mg 30 minutes n = 24 unknown Trend towards increase (mainly during the day) Sleep efficiency increased (mainly biological day) Duffy et al., 202263
Adults aged 56 and over (average 64.2 years) 5 mg 30 minutes n = 24 unknown Significant increase (day and night) Sleep efficiency significantly increased (day and night) Duffy et al, 202263
Adults with chronic insomnia, 70-90 years 2 mg immediate release 2 hours n = 24 Significant improvement after 1 week unknown Sleep efficiency: 78.8% (vs. 77.4% placebo) Haimov et al., 1995 64
Adults with chronic insomnia, 70-90 years 2 mg sustained release 2 hours n = 24 Significant improvement after 1 week unknown Sleep efficiency: 80.4% (vs. 77.4% placebo) Haimov et al., 1995 64
Adults with chronic insomnia, 70-90 years 1 mg sustained release 2 hours n = 17 Significant improvement after 2 months unknown Sleep efficiency: 84.3% (vs. 77.4% placebo) Haimov et al., 1995 64
Adults with primary insomnia
Target group Dose Intake before sleep Number of subjects Sleep onset latency Sleep duration Sleep quality / sleep efficiency Study
Healthy middle-aged subjects 0.3 mg immediate release in the evening before bedtime n = 15 (crossover) 4.1 min faster, 5.8 min earlier 8.4 min longer Sleep efficiency tends to increase Attenburow et al., 199665
Healthy middle-aged subjects 1.0 mg immediate release in the evening before bedtime n = 15 (crossover) 3.6 min faster, 10.9 min earlier 21.6 min longer (significant) Sleep efficiency significantly increased Attenburow et al., 199665
Adults with primary insomnia, 18-80 y. 2 mg sustained release (PRM) 2 h before bedtime, 3 weeks + 26 weeks n = 791 19.1 min faster at ≥ 55 y. approx. 40 min longer PSQI and WHO-5 significantly improved Wade et al., 201066
Adults with intellectual disabilities
Target group Dose Intake before sleep Number of subjects Sleep onset latency Sleep duration Sleep quality / sleep efficiency Study
Adults and children with intellectual disability and chronic insomnia 5 mg immediate release 30 min before bedtime, 4 weeks n = 51 29 min shorter, 34 min earlier (p < 0.001) 48 min longer 40 % less frequent waking/night Braam et al., 200867
Adults with ID and chronic insomnia (follow-up RCT on daytime behavior) 5 mg immediate release 30 min before bedtime, 4 weeks N = 49, n = 27 40 min faster 53 min longer 30 % fewer night-time awakenings, challenging behavior significantly reduced during the day Braam et al., 201068
Adults and children with ID 0.5-10 mg immediate release or sustained release variable 34 min faster 50 min longer nocturnal awakening reduced Braam et al, 2009 (mata study, k = 9 RCTs, n = 183)69
Adults: Seniors with insomnia and dementia
Target group Dose Intake before sleep Number of subjects Sleep onset latency (SOL) Sleep duration Sleep quality / sleep efficiency Study
Elderly patients (~ 76 yrs) with insomnia and chronic diseases 2 mg sustained release 2 h before bedtime, 3 weeks n = 12 (crossover) SOL 24 min faster (not significant), WASO 49 min shorter (significant) unchanged Sleep efficiency and subjective sleep quality significantly improved Garfinkel et al., 199570
Patients with Alzheimer’s dementia and nocturnal sleep disturbance 2.5 mg sustained release or 10 mg immediate release 1 h before bedtime, 8 weeks n = 157 (3-arm) unchanged (actigraphic) unchanged (actigraphic) Trends, but no significant effects Singer et al., 200371
Patients with institutionalized Alzheimer’s dementia 8.5 mg immediate release + 1.5 mg sustained release 22:00, 10 days N = 41 unchanged (actigraphic) unchanged (actigraphic) nchanged (actigraphic); agitation also unchanged Gehrman et al., 200972
Patients with mild to moderate Alzheimer’s dementia, 75 yrs. 2 mg sustained release (add-on to standard therapy) 1-2 hrs before bedtime, 24 weeks n = 80 unknown unknown PSQI significantly improved; ADAS-Cog and IADL significantly better in Alzheimer’s with insomnia Wade et al, 201473
Adults with Parkinson’s
Target group Dose Intake before sleep Number of subjects Sleep onset latency Sleep duration Sleep quality / sleep efficiency Study
Parkinson’s with sleep disturbance 3 mg immediate release 30 min before bedtime, 2 weeks n = 18 not significant (PSG) not significant subjective sleep quality (GSDS) improved; PSG parameters unchanged Medeiros et al., 200774
Parkinson’s with REM sleep behavior disorder 4 mg sustained release immediately before bedtime, 8 weeks n = 30 unknown unchanged No significant reduction in REM sleep disorder Gilat et al., 202075
Parkinson’s with sleep disturbance 50 mg (very high dose) 30 min before bedtime, 2 weeks n = 40 unknown 5 min longer (5 mg) , 8 min longer (50 mg) subjective sleep quality significantly improved Dowling et al., 200576
Adults: Shift workers
Target group Dose Intake before sleep Number of subjects Sleep onset latency Sleep duration Sleep quality / sleep efficiency Study
Nurses on night shift, 24-46 y. 5 mg immediate release 30 min before daytime sleep after night shift n = 86 (crossover) subjective SOL significantly shortened vs. placebo and baseline unchanged unchanged Sadeghniiat-Haghighi et al, 200877
Shift workers with sleep onset disorder, medium ~ 36 y. 3 mg immediate release 30 min before daytime sleep n = 39 (crossover) SOL 7 min faster (actigraphy, p < 0.05), WASO not significant TST not significant Sleep efficiency significantly increased Sadeghniiat-Haghighi et al., 201678
Young adults (27 y.) in simulated night shift (8 h daytime sleep) 1.8 mg sustained release 30 min before daytime sleep n = 21 (crossover) unknown Loss of daytime sleep time prevented on first day; stronger in “poor daytime sleepers” no hangover effects; MSLT unchanged Sharkey et al., 200179
Nurses on night shift 6 mg immediate release 30 min before daytime sleep n = 47 TST significantly increased during daytime sleep TST +94 min on some days subjective sleep quality not significantly source not verifiable
Adults: Jetlag
Target group Dose Intake before sleep Number of subjects Sleep onset latency Sleep duration Sleep quality / sleep efficiency Study
Travelers after eastbound flight over 6-8 time zones 5 mg immediate release at bedtime at destination, 4 days n = 234 SOL significantly shorter (p < 0.05) unknown Sleep quality significantly improved. Suhner et al, 199880
Travelers after eastbound flight over 6-8 time zones 0.5 mg immediate release at bedtime at destination, 4 days n = 234 tended to be shortened (less than 5 mg) unknown tended to be improved (less than 5 mg) Suhner et al., 199880
Travelers after eastbound flight over 6-8 time zones 2 mg sustained release at bedtime at destination, 4 days n = 234 not significant unknown less effective than immediate release Suhner et al., 199880
Travelers after eastern flight (Cochrane meta-analysis) 0.5-5 mg sustained release near destination bedtime (10-24 pm) 10 RCTs Jet lag symptoms significantly reduced in 9/10 studies not systematically evaluated Sleep quality significantly better at 5 mg vs. 0.5 mg; higher doses not helpful; sustained release melatonin had worse effect Herxheimer & Petrie 2002 (Cochrane)81
Insomnia with comorbidities
Target group Dose Intake before sleep Number of subjects Sleep onset latency Sleep duration Sleep quality / sleep efficiency Study
Internal medicine inpatients with difficulty falling asleep Mean stable dose 5.4 mg immediate release (flexible) In the evening before bedtime, 8-16 days N = 33, n = 18 Significantly accelerated sleep onset (p < 0.05) Sleep duration significantly increased Sleep quality and depth significantly improved; no hangover Andrade et al., 200182
Ventilated intensive care patients after tracheostomy 10 mg 21:00, 4 nights n = 24 unknown 60 min longer Sleep efficiency tends to be better; lower doses (1-2 mgI) may be better Bourne et al., 200883
Hemodialysis patients with insomnia 3 mg immediate release at bedtime = 22:00, 6 weeks n = 50 (crossover) SOL 21 min faster (actigraphy) 1 h longer (p < 0.01) Sleep efficiency significantly increased Edalat-Nejad et al., 201384
Patients with chronic obstructive pulmonary disease (COPD) 3 mg immediate release 22:00, 3 months n = 25, n = 12 shortened (p = 0.008) extended (p = 0.046) PSQI total score and sleep disturbance subscale significantly improved Nunes et al., 200885
Breast cancer patients with insomnia (30-75 yrs) 6 mg immediate release 30 min before bedtime, 8 weeks n = 43 unknown 37 min longer PSQI total score and subscales (sleep disturbance, sleep quality, sleep duration) significantly improved Hansen et al., 201486

2.2. Melatonin 7 hours before sleep: sleep phase is shifted forward

The circadian rhythm can be shifted forward or backward by administering melatonin at appropriate times.87 The so-called phase-advance zone for melatonin, in which it shifts the circadian rhythm forward, is the period in the afternoon or early evening. This can help to treat delayed sleep phases, such as delayed sleep phase syndrome (DSPS, also known as DSWPD or ZSPS), which is common in ADHD, or jet lag to the east.88 The phase-advance zone for melatonin comprises CT 6 to CT 18, the phase-delay zone CT 18 to CT 6.89
Delayed melatonin secretion is thought to play a key role in the pathophysiology of DSPS.

Delayed Sleep Phase Syndrome (DSPS) must be diagnosed,

  • when
    • Problems falling asleep at the desired bedtime after 11:30 p.m. and/or
    • Sleep onset latency of more than 30 minutes
  • lead to daytime impairments of social and/or occupational functioning, and
  • Symptoms
    • have existed for at least 6 months
    • cannot be explained by other factors

2.2. Melatonin according to DLMO: sleep phase shifted backwards

Taking melatonin in the middle of the night or directly after waking up can shift the circadian melatonin rhythm backwards.

3. Miscellaneous about melatonin

The daily doses of melatonin as a medication range from 0.5 milligrams to 8 milligrams.

Sustained release melatonin should only be used in the event of complete failure of melatonin production90

3.1. Synthesis of melatonin

Melatonin is formed in the pinealocytes of the pineal gland from L-tryptophan via the intermediate stages 5-hydroxytryptophan and serotonin. The last two steps (N-acetylation by AANAT, methylation by ASMT/HIOMT) are regulated night-specifically.
L-tryptophan → 5-HTP (through tryptophan hydroxylase) → serotonin (through AADC) → N-acetylserotonin (through AANAT) → melatonin (through HIOMT/ASMT).

Brightness is registered by retinal ganglion cells containing melanopsin and suppresses melatonin synthesis in the pineal gland via the suprachiasmatic nucleus (SCN).
This inhibition ceases in darkness. Then the SCN activates noradrenergic fibers to the pineal gland via the paraventricular nucleus, the spinal intermediolateral column and the cervical ganglion superius, which induces AANAT and increases melatonin release.

3.2. What is influenced by melatonin

Melatonin stabilizes and strengthens the coupling of circadian rhythms, especially core temperature and the sleep-wake rhythm.
Melatonin also appears to influence the circadian organization of several other physiological functions, such as91

  • antioxidant defense
  • Hemostasis
  • Glucose regulation
  • Immune defense
    • Pro-inflammatory cytokines (esp. IL-6) show nocturnal peak at low cortisol (which is influenced by melatonin)
      • Example: morning joint stiffness in rheumatoid arthritis 92
    • The immune system is circadian controlled93
  • Dexamethasone induces circadian gene expression in cultured fibroblasts and transiently shifts phasing in liver, kidney and heart, but not in SCN94
  • Core body temperature
    • Melatonin peak in normal state is approx. 1.8 ± 0.2 h before the temperature minimum95
    • Melatonin rhythm is less easily influenced by environmental factors (apart from light) than body temperature. Melatonin therefore a more reliable marker for the circadian phase than core body temperature9697
    • the temporal course of the drop in core body temperature is closely linked to nocturnal melatonin secretion (r = 0.97). Melatonin is causally responsible for at least 40 % of the amplitude of the temperature rhythm.
      Suppression of melatonin secretion with the β-blocker atenolol attenuated the nocturnal drop in temperature. Melatonin administration lowered the temperature during the day.98
    • The DLMO occurs approximately 7 hours before the body core temperature minimum and 1.25 hours before the end of melatonin synthesis.99100

3.3. Degradation of melatonin

Due to the degradation of melatonin via CYP1A2 and (to a lesser extent) CYP2C19, increased caution should be exercised when combining melatonin with drugs that are also degraded via these pathways.
This mechanism also explains the fatigue-promoting effect of imipramine/desipramine, which, if severe, means that imipramine should be taken in the evening.

A decrease in the effect of melatonin could be due to CYP1A2 underactivity. In this case, a reduction in dosage is recommended.101

3.4. Measurement of melatonin

Melatonin is released from the time it gets dark, whereby the release initially increases slowly and usually more quickly between 10 and 11 p.m. (acrophase). The high melatonin level drops again from around 2 am to 4 am.90

A measurement can be made using serum, the first morning urine or saliva.
A measurement based on the serum or the first morning urine is not suitable for determining the daily profile.

3.5. Risks and side effects of melatonin

Melatonin appears to be a safe remedy for improving sleep problems in children and adults with ADHD. The large amount of use, the long duration of use in the respective persons with ADHD and the increasing numbers of use indicate evidence for successful use. The fact that there are only a few large clinical studies on the use of melatonin for sleep problems in ADHD is probably also due to the fact that off-patent active ingredients (such as melatonin) are understandably not of commercial interest to pharmaceutical companies. It is not the task of pharmaceutical companies to investigate the efficacy or safety of off-patent active ingredients. On the contrary, there would be more of an economic interest in identifying negative aspects of melatonin in order to avoid competition from melatonin as an active ingredient in the public domain. However, such reports are also lacking.

We could not find any studies documenting the occurrence of relevant side effects of melatonin. In view of the high number of users and the long history of use for the treatment of sleep problems, including in children and adults with ADHD, we consider the absence of reports of side effects to be an indication of good tolerability.
Nevertheless, there are reports of side effects of melatonin when taken continuously. In these cases, intermittent use is probably recommended, with a 1 to 2 day break every 1 to 2 weeks.

A review states that no relevant side effects of melatonin are known.101

Adults produce approximately 20 to 60 micrograms of melatonin daily. Melatonin is rapidly absorbed and metabolized on the first pass through the liver, with a half-life of 30 to 40 minutes (in 3- to 8-year-old children as well as adults, while newborns showed a half-life of up to 20 hours) and a bioavailability of 1 to 37%. In the liver, it is metabolized by CYP1A220 to 6-hydroxymelatonin and then sulfated to 6-sulfatoxymelatonin or conjugated to glucuronide and excreted.102

Too high a melatonin level can cause depression (winter depression).
Possible side effects can be

  • Night sweats103
  • Hot flushes at night103
  • Mood changes103
    • Restlessness
    • Nervousness
    • Fear
    • Lethargy
  • Nightmares
    • Occasionally (in 1 in 100-1,000 people treated) to rarely (in 1 in 1,000-10,000 people treated)104
  • Very vivid dreams
    • Occasionally to rarely104
  • Stomach cramps
    • Occasionally to rarely104
  • Dizziness
    • Occasionally to rarely104
  • Headache
    • Occasionally to rarely104
  • Irritability
    • Occasionally to rarely104
  • Reduced sexual desire
    • Occasionally to rarely104

3.6. Interactions with melatonin

Interactions with antithrombotic and antiepileptic drugs are possible.

3.6.1. Reducing the effect of melatonin

  • Some psychotropic drugs90
  • Alpha blocker90
  • Beta blockers90
  • Alcohol
    • Even moderate doses of alcohol, one hour before bedtime, caused a significant reduction in melatonin levels in young adults.105

3.6.2. Increasing the effect of melatonin

Due to the degradation mechanism, inhibitors of CYP1A2 and CYP2C19 increase the plasma levels and bioavailability of melatonin:

  • Fluvoxamine106107
    • Inhibits the breakdown of melatonin in the liver; increases the duration and effectiveness of melatonin90
  • Desipramine106
    • Consequently also imipramine, as this is converted to desipramine
  • Caffeine108
  • Theophylline102
  • Citalopram / escitalopram as a CYP2C19 inhibitor109
  • Ciprofloxacin
    • Inhibits the breakdown of melatonin in the liver; increases the duration and effectiveness of melatonin90

3.6.3. Melatonin increases the effect of other medications

Melatonin enhances the dampening effect of, among other things:90

  • Benzodiazepines
  • Zaleplon
  • Zopiclone
  • Zolpidem
  • Imipramine
  • Thioridazine

  1. Skene, Lockley, Arendt (1999): Melatonin in circadian sleep disorders in the blind. Biol Signals Recept. 1999 Jan-Apr;8(1-2):90-5. doi: 10.1159/000014575. PMID: 10085469. ↥

  2. https://www.apotheke-adhoc.de/nachrichten/detail/apothekenpraxis/melatonin-rechtslage-ungewiss-arzneimittel-oder-lebensmittel/ ↥

  3. Rolling J, Rabot J, Schroder CM (2022): Melatonin Treatment for Pediatric Patients with Insomnia: Is There a Place for It? Nat Sci Sleep. 2022 Oct 27;14:1927-1944. doi: 10.2147/NSS.S340944. PMID: 36325278; PMCID: PMC9621019. REVIEW ↥

  4. Cummings (2012): Canadian Paediatric Society, Community Paediatrics Committee. Melatonin for the management of sleep disorders in children and adolescents. Paediatr Child Health. 2012 Jun;17(6):331-6. PMID: 23730172; PMCID: PMC3380753. ↥

  5. Holvoet, Gabriëls (2013): Verstoorde slaap bij kinderen met ADHD: heeft melatonine een plaats in de behandeling? [Disturbed sleep in children with ADHD: is there a place for melatonin as a treatment option?]. Tijdschr Psychiatr. 2013;55(5):349-57. Dutch. PMID: 23696337. ↥

  6. Bijlenga, Vollebregt, Kooij, Arns (2019): The role of the circadian system in the etiology and pathophysiology of ADHD: time to redefine ADHD? Atten Defic Hyperact Disord. 2019 Mar;11(1):5-19. doi: 10.1007/s12402-018-0271-z. ↥

  7. Coogan, McGowan (2017): A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder. Atten Defic Hyperact Disord. 2017 Sep;9(3):129-147. doi: 10.1007/s12402-016-0214-5. PMID: 28064405. n = 62 Studien, n = 4.462, REVIEW ↥

  8. Cortese, Brown, Corkum, Gruber, O’Brien, Stein, Weiss, Owens (2013): Assessment and management of sleep problems in youths with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2013 Aug;52(8):784-96. doi: 10.1016/j.jaac.2013.06.001. PMID: 23880489. ↥

  9. van Geijlswijk, Korzilius, Smits (2010):. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep. 2010 Dec;33(12):1605-14. doi: 10.1093/sleep/33.12.1605. PMID: 21120122; PMCID: PMC2982730. n = 9 Studien ↥ ↥

  10. Stein, Zulauf-McCurdy, DelRosso (2022): Attention Deficit Hyperactivity Disorder Medications and Sleep. Child Adolesc Psychiatr Clin N Am. 2022 Jul;31(3):499-514. doi: 10.1016/j.chc.2022.03.006. PMID: 35697398. REVIEW ↥

  11. Salanitro M, Wrigley T, Ghabra H, de Haan E, Hill CM, Solmi M, Cortese S. (2022): Efficacy on sleep parameters and tolerability of melatonin in individuals with sleep or mental disorders: a systematic review and meta-analysis. Neurosci Biobehav Rev. 2022 Jun 9:104723. doi: 10.1016/j.neubiorev.2022.104723. PMID: 35691474. ↥

  12. Kooij (2019): ADHD and Sleep Webinar ↥

  13. Moon E, Kim K, Partonen T, Linnaranta O (2022): Role of Melatonin in the Management of Sleep and Circadian Disorders in the Context of Psychiatric Illness. Curr Psychiatry Rep. 2022 Nov;24(11):623-634. doi: 10.1007/s11920-022-01369-6. PMID: 36227449; PMCID: PMC9633504. REVIEW ↥

  14. Krause, Krause (2014): ADHS im Erwachsenenalter: Symptome – Differenzialdiagnose – Therapie ↥

  15. Herman (2015): Attention Deficit/Hyperactivity Disorder and Sleep in Children. Sleep Med Clin. 2015 Jun;10(2):143-9. doi: 10.1016/j.jsmc.2015.02.003. PMID: 26055862. REVIEW ↥

  16. Larsson I, Aili K, Lönn M, Svedberg P, Nygren JM, Ivarsson A, Johansson P (2022): Sleep interventions for children with attention deficit hyperactivity disorder (ADHD): A systematic literature review. Sleep Med. 2022 Dec 26;102:64-75. doi: 10.1016/j.sleep.2022.12.021. PMID: 36603513. REVIEW ↥

  17. Checa-Ros A, Muñoz-Hoyos A, Molina-Carballo A, Viejo-Boyano I, Chacín M, Bermúdez V, D’Marco L (2023): Low Doses of Melatonin to Improve Sleep in Children with ADHD: An Open-Label Trial. Children (Basel). 2023 Jun 28;10(7):1121. doi: 10.3390/children10071121. PMID: 37508618; PMCID: PMC10378280. ↥

  18. Bloch, Mulqueen (2014): Nutritional supplements for the treatment of ADHD. Child Adolesc Psychiatr Clin N Am. 2014 Oct;23(4):883-97. doi: 10.1016/j.chc.2014.05.002.PMID: 25220092; PMCID: PMC4170184. REVIEW ↥

  19. Masi, Fantozzi, Villafranca, Tacchi, Ricci, Ruglioni, Inguaggiato, Pfanner, Cortese (2019): Effects of melatonin in children with attention-deficit/hyperactivity disorder with sleep disorders after methylphenidate treatment; Neuropsychiatr Dis Treat. 2019; 15: 663–667. doi: 10.2147/NDT.S193891, PMCID: PMC6410756, PMID: 30880992 ↥

  20. Ayyash, Preece, Morton, Cortese (2015): Melatonin for sleep disturbance in children with neurodevelopmental disorders: prospective observational naturalistic study. Expert Rev Neurother. 2015 Jun;15(6):711-7. doi: 10.1586/14737175.2015.1041511. PMID: 25938708. n = 38 ↥

  21. Barrett, Tracy, Giaroli (2013): To sleep or not to sleep: a systematic review of the literature of pharmacological treatments of insomnia in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2013 Dec;23(10):640-7. doi: 10.1089/cap.2013.0059. PMID: 24261659; PMCID: PMC3870602. REVIEW ↥

  22. Bendz, Scates (2009): Melatonin treatment for insomnia in pediatric patients with attention-deficit/hyperactivity disorder. Ann Pharmacother. 2010 Jan;44(1):185-91. doi: 10.1345/aph.1M365. PMID: 20028959. METASTUDY ↥

  23. Parvataneni, Srinivas, Shah, Patel (2020): Perspective on Melatonin Use for Sleep Problems in Autism and Attention-Deficit Hyperactivity Disorder: A Systematic Review of Randomized Clinical Trials. Cureus. 2020 May 28;12(5):e8335. doi: 10.7759/cureus.8335. PMID: 32617211; PMCID: PMC7325410. METASTUDIE ↥

  24. Rzepka-Migut, Paprocka (2020): Efficacy and Safety of Melatonin Treatment in Children with Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder-A Review of the Literature. Brain Sci. 2020 Apr 7;10(4):219. doi: 10.3390/brainsci10040219. PMID: 32272607; PMCID: PMC7226342. REVIEW ↥

  25. Um, Hong, Jeong (2017): Sleep Problems as Predictors in Attention-Deficit Hyperactivity Disorder: Causal Mechanisms, Consequences and Treatment. Clin Psychopharmacol Neurosci. 2017 Feb 28;15(1):9-18. doi: 10.9758/cpn.2017.15.1.9. PMID: 28138105; PMCID: PMC5290714. REVIEW ↥

  26. Kimland, Bardage, Collin, Järleborg, Ljung, Iliadou (2020): Pediatric use of prescribed melatonin in Sweden 2006-2017: a register based study. Eur Child Adolesc Psychiatry. 2020 Jul 22. doi: 10.1007/s00787-020-01598-1. PMID: 32699990. KOHORTENSTUDIE ↥

  27. Furster, Hallerbäck (2015): The use of melatonin in Swedish children and adolescents–a register-based study according to age, gender, and medication of ADHD. Eur J Clin Pharmacol. 2015 Jul;71(7):877-81. doi: 10.1007/s00228-015-1866-3. PMID: 25995170. n = 7.389, KOHORTENSTUDIE ↥

  28. Hartz, Handal, Tverdal, Skurtveit (2015): Paediatric Off-Label Use of Melatonin–A Register Linkage Study between the Norwegian Prescription Database and Patient Register. Basic Clin Pharmacol Toxicol. 2015 Oct;117(4):267-73. doi: 10.1111/bcpt.12411. PMID: 25892306. KOHORTENSTUDIE ↥

  29. Furu, Karlstad, Zoega, Martikainen, Bahmanyar, Kieler, Pottegård (2017): Utilization of Stimulants and Atomoxetine for Attention-Deficit/Hyperactivity Disorder among 5.4 Million Children Using Population-Based Longitudinal Data. Basic Clin Pharmacol Toxicol. 2017 Apr;120(4):373-379. doi: 10.1111/bcpt.12724. Epub 2017 Jan 30. PMID: 27911044. n = 48.296, KOHORTENSTUDIE ↥

  30. Bock, Roach-Fox, Seabrook, Rieder, Matsui (2015): Sleep-promoting medications in children: physician prescribing habits in Southwestern Ontario, Canada. Sleep Med. 2016 Jan;17:52-6. doi: 10.1016/j.sleep.2015.10.003. PMID: 26847974. ↥

  31. Fukumizu, Hayashi, Miyajima, Ishizaki, Tanaka, Kohyama (2015): [A nationwide survey on the uses of melatonin and ramelteon in Japanese children]. No To Hattatsu. 2015 Jan;47(1):23-7. Japanese. PMID: 25803907. ↥

  32. Hayashi M, Mishima K, Fukumizu M, Takahashi H, Ishikawa Y, Hamada I, Sugioka H, Yotsuya O, Yamashita Y (2022): Melatonin Treatment and Adequate Sleep Hygiene Interventions in Children with Autism Spectrum Disorder: A Randomized Controlled Trial. J Autism Dev Disord. 2022 Jun;52(6):2784-2793. doi: 10.1007/s10803-021-05139-w. PMID: 34181143. ↥ ↥ ↥

  33. Williams Buckley A, Hirtz D, Oskoui M, Armstrong MJ, Batra A, Bridgemohan C, Coury D, Dawson G, Donley D, Findling RL, Gaughan T, Gloss D, Gronseth G, Kessler R, Merillat S, Michelson D, Owens J, Pringsheim T, Sikich L, Stahmer A, Thurm A, Tuchman R, Warren Z, Wetherby A, Wiznitzer M, Ashwal S (2020): Practice guideline: Treatment for insomnia and disrupted sleep behavior in children and adolescents with autism spectrum disorder: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2020 Mar 3;94(9):392-404. doi: 10.1212/WNL.0000000000009033. PMID: 32051244; PMCID: PMC7238942. ↥

  34. Palagini, Manni, Aguglia, Amore, Brugnoli, Bioulac, Bourgin, Micoulaud Franchi, Girardi, Grassi, Lopez, Mencacci, Plazzi, Maruani, Minervino, Philip, Royant Parola, Poirot, Nobili, Biggio, Schroder, Geoffroy (2021): International Expert Opinions and Recommendations on the Use of Melatonin in the Treatment of Insomnia and Circadian Sleep Disturbances in Adult Neuropsychiatric Disorders. Front Psychiatry. 2021 Jun 10;12:688890. doi: 10.3389/fpsyt.2021.688890. PMID: 34177671; PMCID: PMC8222620. REVIEW ↥

  35. Geoffroy, Micoulaud Franchi, Lopez, Schroder (2019): membres du consensus Mélatonine SFRMS. The use of melatonin in adult psychiatric disorders: Expert recommendations by the French institute of medical research on sleep (SFRMS). Encephale. 2019 Nov;45(5):413-423. doi: 10.1016/j.encep.2019.04.068. PMID: 31248601. ↥

  36. van Geijlswijk, Korzilius, Smits (2010):. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep. 2010 Dec;33(12):1605-14. doi: 10.1093/sleep/33.12.1605. PMID: 21120122; PMCID: PMC2982730. METASTUDY ↥

  37. Maruani J, Reynaud E, Chambe J, Palagini L, Bourgin P, Geoffroy PA (2023): Efficacy of melatonin and ramelteon for the acute and long-term management of insomnia disorder in adults: A systematic review and meta-analysis. J Sleep Res. 2023 Dec;32(6):e13939. doi: 10.1111/jsr.13939. PMID: 37434463. METASTUDY ↥

  38. Bruno S, Cenerini G, Lo Giudice L, Cruz-Sanabria F, Benedetti D, Crippa A, Fiori S, Ferri R, Masi G, Faraguna U (2025): Optimizing timing and dose of exogenous melatonin administration in neuropsychiatric pediatric populations: a meta-analysis on sleep outcomes. Sleep Med Rev. 2025 Dec;84:102158. doi: 10.1016/j.smrv.2025.102158. PMID: 40914024. METASTUDY ↥

  39. Cruz-Sanabria F, Bruno S, Crippa A, Frumento P, Scarselli M, Skene DJ, Faraguna U (2024): Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis. J Pineal Res. 2024 Aug;76(5):e12985. doi: 10.1111/jpi.12985. PMID: 38888087. METASTUDY ↥

  40. Weiss MD, Wasdell MB, Bomben MM, Rea KJ, Freeman RD (2006): Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia. J Am Acad Child Adolesc Psychiatry. 2006 May;45(5):512-519. PMID: 16670647. ↥

  41. Mohammadi MR, Mostafavi SA, Keshavarz SA, Eshraghian MR, Hosseinzadeh P, Hosseinzadeh-Attar MJ, Kooshesh SM, Chamari M, Akhondzadeh S (2012): Melatonin effects in methylphenidate treated children with attention deficit hyperactivity disorder: a randomized double blind clinical trial. Iran J Psychiatry. 2012 Spring;7(2):87-92. PMID: 22952551; PMCID: PMC3428643. ↥

  42. Masi, Fantozzi, Villafranca, Tacchi, Ricci, Ruglioni, Inguaggiato, Pfanner, Cortese (2019): Effects of melatonin in children with attention-deficit/hyperactivity disorder with sleep disorders after methylphenidate treatment. Neuropsychiatr Dis Treat. 2019 Mar 7;15:663-667. doi: 10.2147/NDT.S193891. PMID: 30880992; PMCID: PMC6410756. n = 74 ↥

  43. Tjon Pian Gi CV, Broeren JPA, Starreveld JS, A Versteegh FG (2003): Melatonin for treatment of sleeping disorders in children with attention deficit/hyperactivity disorder: a preliminary open label study. Eur J Pediatr. 2003 Jul;162(7-8):554-555. doi: 10.1007/s00431-003-1207-x. PMID: 12783318. n = 24 ↥

  44. Mostafavi, Mohammadi, Hosseinzadeh, Eshraghian, Akhondzadeh, Hosseinzadeh-Attar, Ranjbar, Kooshesh, Keshavarz (2012): Dietary intake, growth and development of children with ADHD in a randomized clinical trial of Ritalin and Melatonin co-administration: Through circadian cycle modification or appetite enhancement? Iran J Psychiatry. 2012 Summer;7(3):114-9. PMID: 23139692; PMCID: PMC3488866. n = 50 ↥

  45. Sletten TL, Magee M, Murray JM, Gordon CJ, Lovato N, Kennaway DJ, Gwini SM, Bartlett DJ, Lockley SW, Lack LC, Grunstein RR, Rajaratnam SMW; Delayed Sleep on Melatonin (DelSoM) Study Group (2018): Efficacy of melatonin with behavioural sleep-wake scheduling for delayed sleep-wake phase disorder: A double-blind, randomised clinical trial. PLoS Med. 2018 Jun 18;15(6):e1002587. doi: 10.1371/journal.pmed.1002587. PMID: 29912983; PMCID: PMC6005466. ↥

  46. Cortesi F, Giannotti F, Sebastiani T, Panunzi S, Valente D (2012): Controlled-release melatonin, singly and combined with cognitive behavioural therapy, for persistent insomnia in children with autism spectrum disorders: a randomized placebo-controlled trial. J Sleep Res. 2012 Dec;21(6):700-9. doi: 10.1111/j.1365-2869.2012.01021.x. PMID: 22616853. ↥

  47. Gringras P, Nir T, Breddy J, Frydman-Marom A, Findling RL (2017): Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children With Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry. 2017 Nov;56(11):948-957.e4. doi: 10.1016/j.jaac.2017.09.414. PMID: 29096777. ↥

  48. Wright B, Sims D, Smart S, Alwazeer A, Alderson-Day B, Allgar V, Whitton C, Tomlinson H, Bennett S, Jardine J, McCaffrey N, Leyland C, Jakeman C, Miles J (2011): Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: a randomised controlled crossover trial. J Autism Dev Disord. 2011 Feb;41(2):175-84. doi: 10.1007/s10803-010-1036-5. PMID: 20535539. ↥

  49. Garstang J, Wallis M (2006): Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems. Child Care Health Dev. 2006 Sep;32(5):585-9. doi: 10.1111/j.1365-2214.2006.00616.x. PMID: 16919138. ↥

  50. Wirojanan J, Jacquemont S, Diaz R, Bacalman S, Anders TF, Hagerman RJ, Goodlin-Jones BL (2009): The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome. J Clin Sleep Med. 2009 Apr 15;5(2):145-50. Erratum in: J Clin Sleep Med. 2010 Aug 15;6(4):preceding 311. PMID: 19968048; PMCID: PMC2670334. ↥

  51. Malow B, Adkins KW, McGrew SG, Wang L, Goldman SE, Fawkes D, Burnette C (2012): Melatonin for sleep in children with autism: a controlled trial examining dose, tolerability, and outcomes. J Autism Dev Disord. 2012 Aug;42(8):1729-37; author reply 1738. doi: 10.1007/s10803-011-1418-3. PMID: 22160300; PMCID: PMC3368078. ↥

  52. Paavonen EJ, Nieminen-von Wendt T, Vanhala R, Aronen ET, von Wendt L (2003): Effectiveness of melatonin in the treatment of sleep disturbances in children with Asperger disorder. J Child Adolesc Psychopharmacol. 2003 Spring;13(1):83-95. doi: 10.1089/104454603321666225. PMID: 12804129. ↥

  53. Wasdell MB, Jan JE, Bomben MM, Freeman RD, Rietveld WJ, Tai J, Hamilton D, Weiss MD (2008): A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities. J Pineal Res. 2008 Jan;44(1):57-64. doi: 10.1111/j.1600-079X.2007.00528.x. PMID: 18078449. ↥

  54. Gringras P, Gamble C, Jones AP, Wiggs L, Williamson PR, Sutcliffe A, Montgomery P, Whitehouse WP, Choonara I, Allport T, Edmond A, Appleton R; MENDS Study Group (2012): Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial. BMJ. 2012 Nov 5;345:e6664. doi: 10.1136/bmj.e6664. PMID: 23129488; PMCID: PMC3489506. ↥

  55. McArthur AJ, Budden SS (1998): Sleep dysfunction in Rett syndrome: a trial of exogenous melatonin treatment. Dev Med Child Neurol. 1998 Mar;40(3):186-92. doi: 10.1111/j.1469-8749.1998.tb15445.x. PMID: 9566656. ↥

  56. Braam W, Didden R, Smits MG, Curfs LM (2008): Melatonin for chronic insomnia in Angelman syndrome: a randomized placebo-controlled trial. J Child Neurol. 2008 Jun;23(6):649-54. doi: 10.1177/0883073808314153. PMID: 18539989. ↥

  57. Smits MG, van Stel HF, van der Heijden K, Meijer AM, Coenen AM, Kerkhof GA (2003): Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2003 Nov;42(11):1286-93. doi: 10.1097/01.chi.0000085756.71002.86. PMID: 14566165. ↥

  58. Xu H, Zhang C, Qian Y, Zou J, Li X, Liu Y, Zhu H, Meng L, Liu S, Zhang W, Yi H, Guan J, Chen Z, Yin S (2020): Efficacy of melatonin for sleep disturbance in middle-aged primary insomnia: a double-blind, randomised clinical trial. Sleep Med. 2020 Dec;76:113-119. doi: 10.1016/j.sleep.2020.10.018. PMID: 33157425. ↥

  59. Zhdanova IV, Wurtman RJ, Regan MM, Taylor JA, Shi JP, Leclair OU (2001): Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab. 2001 Oct;86(10):4727-30. doi: 10.1210/jcem.86.10.7901. PMID: 11600532. ↥ ↥ ↥

  60. Lemoine P, Nir T, Laudon M, Zisapel N (2007): Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res. 2007 Dec;16(4):372-80. doi: 10.1111/j.1365-2869.2007.00613.x. PMID: 18036082. ↥

  61. Luthringer, Muzet, Zisapel, Staner (2009): Int Clin Psychopharmacol. 2009 Sep;24(5):239-49. doi: 10.1097/YIC.0b013e32832e9b08. The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia. n = 40 ↥

  62. Wade AG, Ford I, Crawford G, McMahon AD, Nir T, Laudon M, Zisapel N (2007): Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2007 Oct;23(10):2597-605. doi: 10.1185/030079907X233098. PMID: 17875243. N = 354 ↥

  63. Duffy JF, Wang W, Ronda JM, Czeisler CA (2022): High dose melatonin increases sleep duration during nighttime and daytime sleep episodes in older adults. J Pineal Res. 2022 Aug;73(1):e12801. doi: 10.1111/jpi.12801. PMID: 35436355; PMCID: PMC9288519. n = 24 ↥ ↥

  64. Haimov I, Lavie P, Laudon M, Herer P, Vigder C, Zisapel N (1995): Melatonin replacement therapy of elderly insomniacs. Sleep. 1995 Sep;18(7):598-603. doi: 10.1093/sleep/18.7.598. PMID: 8552931. n = 24 ↥ ↥ ↥

  65. Attenburrow ME, Cowen PJ, Sharpley AL (1996): Low dose melatonin improves sleep in healthy middle-aged subjects. Psychopharmacology (Berl). 1996 Jul;126(2):179-81. doi: 10.1007/BF02246354. PMID: 8856838. ↥ ↥

  66. Wade AG, Ford I, Crawford G, McConnachie A, Nir T, Laudon M, Zisapel N (2010): Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Med. 2010 Aug 16;8:51. doi: 10.1186/1741-7015-8-51. PMID: 20712869; PMCID: PMC2933606. ↥

  67. Braam W, Didden R, Smits M, Curfs L (2008): Melatonin treatment in individuals with intellectual disability and chronic insomnia: a randomized placebo-controlled study. J Intellect Disabil Res. 2008 Mar;52(Pt 3):256-64. doi: 10.1111/j.1365-2788.2007.01016.x. PMID: 18261024. ↥

  68. Braam W, Didden R, Maas AP, Korzilius H, Smits MG, Curfs LM (2010): Melatonin decreases daytime challenging behaviour in persons with intellectual disability and chronic insomnia. J Intellect Disabil Res. 2010 Jan 1;54(1):52-9. doi: 10.1111/j.1365-2788.2009.01223.x. PMID: 19888921. ↥

  69. Braam W, Smits MG, Didden R, Korzilius H, Van Geijlswijk IM, Curfs LM (2009): Exogenous melatonin for sleep problems in individuals with intellectual disability: a meta-analysis. Dev Med Child Neurol. 2009 May;51(5):340-9. doi: 10.1111/j.1469-8749.2008.03244.x. PMID: 19379289. METASTUDY ↥

  70. Garfinkel D, Laudon M, Nof D, Zisapel N (1995): Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet. 1995 Aug 26;346(8974):541-4. doi: 10.1016/s0140-6736(95)91382-3. PMID: 7658780. ↥

  71. Singer C, Tractenberg RE, Kaye J, Schafer K, Gamst A, Grundman M, Thomas R, Thal LJ; Alzheimer’s Disease Cooperative Study (2003): A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer’s disease. Sleep. 2003 Nov 1;26(7):893-901. doi: 10.1093/sleep/26.7.893. PMID: 14655926; PMCID: PMC4418658. ↥

  72. Gehrman PR, Connor DJ, Martin JL, Shochat T, Corey-Bloom J, Ancoli-Israel S (2009): Melatonin fails to improve sleep or agitation in double-blind randomized placebo-controlled trial of institutionalized patients with Alzheimer disease. Am J Geriatr Psychiatry. 2009 Feb;17(2):166-9. doi: 10.1097/JGP.0b013e318187de18. PMID: 19155748; PMCID: PMC2630117. ↥

  73. Wade AG, Farmer M, Harari G, Fund N, Laudon M, Nir T, Frydman-Marom A, Zisapel N (2014): Add-on prolonged-release melatonin for cognitive function and sleep in mild to moderate Alzheimer’s disease: a 6-month, randomized, placebo-controlled, multicenter trial. Clin Interv Aging. 2014 Jun 18;9:947-61. doi: 10.2147/CIA.S65625. PMID: 24971004; PMCID: PMC4069047. ↥

  74. Medeiros CA, Carvalhedo de Bruin PF, Lopes LA, Magalhães MC, de Lourdes Seabra M, de Bruin VM (2007): Effect of exogenous melatonin on sleep and motor dysfunction in Parkinson’s disease. A randomized, double blind, placebo-controlled study. J Neurol. 2007 Apr;254(4):459-64. doi: 10.1007/s00415-006-0390-x. PMID: 17404779. ↥

  75. Gilat M, Coeytaux Jackson A, Marshall NS, Hammond D, Mullins AE, Hall JM, Fang BAM, Yee BJ, Wong KKH, Grunstein RR, Lewis SJG (2020): Melatonin for rapid eye movement sleep behavior disorder in Parkinson’s disease: A randomised controlled trial. Mov Disord. 2020 Feb;35(2):344-349. doi: 10.1002/mds.27886. PMID: 31674060; PMCID: PMC7027846. ↥

  76. Dowling GA, Mastick J, Colling E, Carter JH, Singer CM, Aminoff MJ (2005): Melatonin for sleep disturbances in Parkinson’s disease. Sleep Med. 2005 Sep;6(5):459-66. doi: 10.1016/j.sleep.2005.04.004. PMID: 16084125. ↥

  77. Sadeghniiat-Haghighi K, Aminian O, Pouryaghoub G, Yazdi Z (2008): Efficacy and hypnotic effects of melatonin in shift-work nurses: double-blind, placebo-controlled crossover trial. J Circadian Rhythms. 2008 Oct 29;6:10. doi: 10.1186/1740-3391-6-10. PMID: 18957133; PMCID: PMC2584099. ↥

  78. Sadeghniiat-Haghighi K, Bahrami H, Aminian O, Meysami A, Khajeh-Mehrizi A (2016): Melatonin therapy in shift workers with difficulty falling asleep: A randomized, double-blind, placebo-controlled crossover field study. Work. 2016 Sep 27;55(1):225-230. doi: 10.3233/WOR-162376. PMID: 27612057. ↥

  79. Sharkey KM, Fogg LF, Eastman CI (2001): Effects of melatonin administration on daytime sleep after simulated night shift work. J Sleep Res. 2001 Sep;10(3):181-92. doi: 10.1046/j.1365-2869.2001.00256.x. PMID: 11696071; PMCID: PMC3679650. ↥

  80. Suhner A, Schlagenhauf P, Johnson R, Tschopp A, Steffen R (1998): Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag. Chronobiol Int. 1998 Nov;15(6):655-66. doi: 10.3109/07420529808993201. PMID: 9844753. ↥ ↥ ↥

  81. Herxheimer A, Petrie KJ (2002): Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev. 2002;(2):CD001520. doi: 10.1002/14651858.CD001520. PMID: 12076414. ↥

  82. Andrade C, Srihari BS, Reddy KP, Chandramma L (2001): Melatonin in medically ill patients with insomnia: a double-blind, placebo-controlled study. J Clin Psychiatry. 2001 Jan;62(1):41-5. doi: 10.4088/jcp.v62n0109. PMID: 11235927. ↥

  83. Bourne RS, Mills GH, Minelli C (2008): Melatonin therapy to improve nocturnal sleep in critically ill patients: encouraging results from a small randomised controlled trial. Crit Care. 2008;12(2):R52. doi: 10.1186/cc6871. PMID: 18423009; PMCID: PMC2447606. ↥

  84. Edalat-Nejad M, Haqhverdi F, Hossein-Tabar T, Ahmadian M (2013): Melatonin improves sleep quality in hemodialysis patients. Indian J Nephrol. 2013 Jul;23(4):264-9. doi: 10.4103/0971-4065.114488. PMID: 23960341; PMCID: PMC3741969. ↥

  85. Nunes DM, Mota RM, Machado MO, Pereira ED, Bruin VM, Bruin PF (2008): Effect of melatonin administration on subjective sleep quality in chronic obstructive pulmonary disease. Braz J Med Biol Res. 2008 Oct;41(10):926-31. doi: 10.1590/s0100-879x2008001000016. PMID: 19030713. ↥

  86. Hansen MV, Madsen MT, Andersen LT, Hageman I, Rasmussen LS, Bokmand S, Rosenberg J, Gögenur I (2014): Effect of Melatonin on Cognitive Function and Sleep in relation to Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial. Int J Breast Cancer. 2014;2014:416531. doi: 10.1155/2014/416531. PMID: 25328711; PMCID: PMC4160608. ↥

  87. Keijzer H, Smits MG, Duffy JF, Curfs LM (2014): Why the dim light melatonin onset (DLMO) should be measured before treatment of patients with circadian rhythm sleep disorders. Sleep Med Rev. 2014 Aug;18(4):333-9. doi: 10.1016/j.smrv.2013.12.001. PMID: 24388969. REVIEW ↥

  88. Pandi-Perumal SR, Smits M, Spence W, Srinivasan V, Cardinali DP, Lowe AD, Kayumov L (2007): Dim light melatonin onset (DLMO): a tool for the analysis of circadian phase in human sleep and chronobiological disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Jan 30;31(1):1-11. doi: 10.1016/j.pnpbp.2006.06.020. PMID: 16884842. REVIEW ↥

  89. Lewy AJ, Ahmed S, Jackson JM, Sack RL (1992): Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiol Int. 1992 Oct;9(5):380-92. doi: 10.3109/07420529209064550. PMID: 1394610. ↥

  90. Wolf, Calabrese (2020): Stressmedizin & Stresspsychologie; Seite 206 ↥ ↥ ↥ ↥ ↥ ↥ ↥ ↥

  91. Claustrat B, Brun J, Chazot G (2005): The basic physiology and pathophysiology of melatonin. Sleep Med Rev. 2005 Feb;9(1):11-24. doi: 10.1016/j.smrv.2004.08.001. PMID: 15649735. ↥

  92. Cutolo M, Masi AT (2005): Circadian rhythms and arthritis. Rheum Dis Clin North Am. 2005 Feb;31(1):115-29, ix-x. doi: 10.1016/j.rdc.2004.09.005. PMID: 15639059. REVIEW ↥

  93. Scheiermann C, Kunisaki Y, Frenette PS (2013): Circadian control of the immune system. Nat Rev Immunol. 2013 Mar;13(3):190-8. doi: 10.1038/nri3386. PMID: 23391992; PMCID: PMC4090048. REVIEW ↥

  94. Balsalobre, Brown, Marcacci, Tronche, Kellendonk, Reichardt, Schütz, Schibler (2000): Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science. 2000 Sep 29;289(5488):2344-7. doi: 10.1126/science.289.5488.2344. PMID: 11009419. ↥

  95. Shanahan TL, Czeisler CA (1991): Light exposure induces equivalent phase shifts of the endogenous circadian rhythms of circulating plasma melatonin and core body temperature in men. J Clin Endocrinol Metab. 1991 Aug;73(2):227-35. doi: 10.1210/jcem-73-2-227. PMID: 1856258. n = 8 ↥

  96. Molina TA, Burgess HJ (2011): Calculating the dim light melatonin onset: the impact of threshold and sampling rate. Chronobiol Int. 2011 Oct;28(8):714-8. doi: 10.3109/07420528.2011.597531. PMID: 21823817; PMCID: PMC3248814. ↥

  97. Benloucif S, Guico MJ, Reid KJ, Wolfe LF, L’hermite-Balériaux M, Zee PC (2005): Stability of melatonin and temperature as circadian phase markers and their relation to sleep times in humans. J Biol Rhythms. 2005 Apr;20(2):178-88. doi: 10.1177/0748730404273983. PMID: 15834114. ↥

  98. Cagnacci A, Elliott JA, Yen SS (1992): Melatonin: a major regulator of the circadian rhythm of core temperature in humans. J Clin Endocrinol Metab. 1992 Aug;75(2):447-52. doi: 10.1210/jcem.75.2.1639946. PMID: 1639946. ↥

  99. Brown EN, Choe Y, Shanahan TL, Czeisler CA; New Collective Author (1997): A mathematical model of diurnal variations in human plasma melatonin levels. Am J Physiol. 1997 Mar;272(3 Pt 1):E506-16. doi: 10.1152/ajpendo.1997.272.3.E506. PMID: 9124558. ↥

  100. Burgess HJ, Eastman CI (2005): The dim light melatonin onset following fixed and free sleep schedules. J Sleep Res. 2005 Sep;14(3):229-37. doi: 10.1111/j.1365-2869.2005.00470.x. PMID: 16120097; PMCID: PMC3841975. ↥

  101. Bruni, Alonso-Alconada, Besag, Biran, Braam, Cortese, Moavero, Parisi, Smits, Van der Heijden, Curatolo (2015): Current role of melatonin in pediatric neurology: clinical recommendations. Eur J Paediatr Neurol. 2015 Mar;19(2):122-33. doi: 10.1016/j.ejpn.2014.12.007. PMID: 25553845. REVIEW ↥ ↥

  102. Kennaway (2015): Potential safety issues in the use of the hormone melatonin in paediatrics. J Paediatr Child Health. 2015 Jun;51(6):584-9. doi: 10.1111/jpc.12840. PMID: 25643981. REVIEW ↥ ↥

  103. Wolf, Calabrese (2020): Stressmedizin & Stresspsychologie; Seite 207 ↥ ↥ ↥

  104. Netdoktor.de: Melatonin ↥ ↥ ↥ ↥ ↥ ↥ ↥

  105. Rupp, Acebo, Carskadon (2007): Evening alcohol suppresses salivary melatonin in young adults. Chronobiol Int. 2007;24(3):463-70. doi: 10.1080/07420520701420675. PMID: 17612945. n = 29 ↥

  106. Skene, Bojkowski, Arendt (1994): Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans. Br J Clin Pharmacol. 1994 Feb;37(2):181-6. doi: 10.1111/j.1365-2125.1994.tb04258.x. PMID: 8186063; PMCID: PMC1364595. ↥ ↥

  107. Härtter, Grözinger, Weigmann, Röschke, Hiemke (2000): Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther. 2000 Jan;67(1):1-6. doi: 10.1067/mcp.2000.104071. PMID: 10668847. ↥

  108. Härtter, Nordmark, Rose, Bertilsson, Tybring, Laine (2003): Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. Br J Clin Pharmacol. 2003 Dec;56(6):679-82. doi: 10.1046/j.1365-2125.2003.01933.x. PMID: 14616429; PMCID: PMC1884289. ↥

  109. Huuhka, Riutta, Haataja, Ylitalo, Leinonen (2006): The effect of CYP2C19 substrate on the metabolism of melatonin in the elderly: A randomized, double-blind, placebo-controlled study. Methods Find Exp Clin Pharmacol. 2006 Sep;28(7):447-50. doi: 10.1358/mf.2006.28.7.1003545. PMID: 17003850. ↥

Previous page Next page