Melatonin, Circadian Rhythms, and Sleep Zhdanova and Tucci 229
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as:
• Of importance
•• Of major importance
1. Tzischinsky O, Shlitner A, Lavie P: The association
between the nocturnal sleep gate and nocturnal onset
of urinary 6-sulfatoxymelatonin.
J Biol Rhythms
2.•• Zhdanova IV, Wurtman RJ, Morabito C,
: Effects of
low oral doses of melatonin, given 2 to 4 hours before
habitual bedtime, on sleep in normal young humans.
The results of the study provide evidence that physiologic
melatonin doses promote earlier sleep onset in healthy young
individuals, treated several hours before their habitual bed-
time, without significantly altering their sleep architecture
3. Zhdanova IV, Wurtman RJ, Lynch HJ,
inducing effects of low doses of melatonin ingested
in the evening.
Clin Pharmacol Ther
4. Zhdanova IV, Wurtman RJ, Regan MM,
treatment for age-related insomnia.
J Clin Endocrinol
5. Stone BM, Turner C, Mills SL, Nicholson AN: Hypnotic
activity of melatonin.
6.•• Zhdanova IV, Piotrovskaya VR: Melatonin reduces
symptoms of acute nicotine withdrawal in humans.
Pharm Biochem Behav
Oral 0.3-mg dose of melatonin administered to habitual
smokers 3.5 hours after the nicotine withdrawal, and increas-
ing circulating melatonin concentrations within the physio-
logic range, attenuates the acute effects of smoking cessation
on mood and reduces cigarette craving.
7.•• Lewy AJ, Bauer VK, Hasler BP,
: Capturing the
circadian rhythms of free-running blind people with
0.5 mg melatonin.
Daily treatment using low-dose (0.5 mg) melatonin can
entrain circadian rhythms in blind people suffering from
free-running circadian rhythms.
8. Wiechmann AF, O'Steen WK: Melatonin increases
photoreceptor susceptibility to light-induced damage.
Invest Ophthalmol Vis Sci
9.•• Arushanian EB, Ovanesov KB: Melatonin lowers the
threshold of light sensitivity of the human retina.
Eksp Klin Farmakol
Chronic melatonin treatment can significantly decrease
retinal sensitivity threshold in older individuals. The authors
suggest a connection between the retinal light sensitivity and
the direct effect of the melatonin on photoreceptors.
10. Stoschitzky K, Sakotnik A, Lercher P,
: Influence of
beta-blockers on melatonin release.
Eur J Clin Pharma-
1999, 55:111 – 11 5 .
11. Palazidou E, Papadopoulos A, Sitsen A,
: An alpha
2 adrenoceptor antagonist, Org 3770, enhances
nocturnal melatonin secretion in man.
12.••Ferini-Strambi L, Zucconi M, Biella G,
of melatonin on sleep microstructure: preliminary
results in healthy subjects.
The authors showed that a combination of melatonin and low
benzodiazepine doses could avoid the residual, dose-related
13. Hartter S, Grozinger M, Weigmann H,
bioavailability of oral melatonin after fluvoxamine
Clin Pharmacol Ther
14.•• Childs PA, Rodin I, Martin NJ,
: Effect of fluoxetine
on melatonin in patients with seasonal affective disorder
and matched controls.
Br J Psychiatry
This study showed that effect of fluoxetine differs from tricyclic
antidepressants and fluvoxamine, which increase melatonin.
15. Demisch L, Demisch K, Nickelsen T: Influence of dexa-
methasone on nocturnal melatonin production in
healthy adult subjects.
J Pineal Res
16.••Hughes RJ, Sack RL, Lewy AJ: The role of melatonin
and circadian phase in age-related sleep-maintenance
insomnia: assessment in a clinical trial of melatonin
1998, 21 :52–68.
The study assessed sleep-promoting effects of fast- and slow-
release melatonin preparations administered at different
times to patients with age-related sleep-maintenance
insomnia. Melatonin treatments shortened latencies to sleep,
demonstrating that high physiologic doses of melatonin can
promote sleep in this population.
17. Middleton B, Arendt J, Stone BM: Complex effects of
melatonin on human circadian rhythms in constant
J Biol Rhythms
18.•• Zhdanova IV, Wurtman RJ, Wagstaff J: Effects of low dose
of melatonin on sleep in children with Angelman
J Pediatr Endocrinol Metab
The authors studied the effects of low-dose (0.3 mg) melato-
nin therapy on sleep and serum melatonin levels in 13
Angelman syndrome children suffering from insomnia, and
found that a moderate overnight increase in circulating
melatonin levels can promote sleep and reduce motor activity
during sleep in these patients.
19. Dollins AB, Zhdanova IV, Wurtman RJ,
: Effect of
inducing nocturnal serum melatonin concentrations in
daytime on sleep, mood, body temperature, and per-
Proc Natl Acad Sci U S A
20.••Galvan Manso M, Campistol J,
syndrome: physical characteristics and behavioral
phenotype in 37 patients with confirmed genetic
The authors reviewed data on multiple physiologic, behavioral,
and sociologic parameters collected from 37 patients with a
positive genetic diagnosis of Angelman syndrome. The sleep
disorders were present in 48% of the patients and required
medication. The most effective treatment for the sleep disorders