Is Melatonin Effective for Sleep - LinkedIn
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Sleep Stage Eye Movements Motor Movements
HR, BP, Respirations
Cerebral Activity
Stage 1 Slow, rolling movements
Moderate activity
Slows Decreases
Stage 2 Slow, rolling movements
Moderate activity
Slows Decreases
Stages 3 & 4 (i.e., deep sleep)
Slow, rolling movements
Moderate activity
Slows Decreases
REM Sleep Clusters of rapid eye movements
Suppressed w loss of muscle
tone
Increases, variable
Increases
Chart adapted from: Porth CM, Sleep and Sleep Disorders. In: Pathophysiology: Concepts of Altered Health States. 8th edition. Porth CM, Matfin G, eds.
Philadelphia: Wolters Kluwer Health; 2009.
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SCN
Forebrain/ThalamusAttention, memory,
emotion, psychomotor performance,
sensorimotor integration
Hypothalamus
Anterior pituitary Hormone levels
HypothalamusBody temperature, metabolism, ANS
function, sleep-wake cycles
Brain stem reticular formation
ANS function, sleep-wake cycles
Pineal gland Melatonin
Light impulses throughretina a,b
Chart adapted from: Porth CM, Sleep and Sleep Disorders. In: Pathophysiology: Concepts of Altered Health States. 8th edition. Porth CM, Matfin G, eds. Philadelphia: Wolters Kluwer Health; 2009.
a Light = inhibitory signalsb Dark (i.e., lack of light) = stimulating signals
https://www.researchgate.net/figure/40454967_fig1_ Figure- 1-Physio log y-of-Melaton in-Secre tion-Me lat onin
MT1 Receptors in SCN
Forebrain/ThalamusAttention, memory,
emotion, psychomotor performance,
sensorimotor integration
Hypothalamus
Anterior pituitary Hormone levels
HypothalamusBody temperature, metabolism, ANS
function, sleep-wake cycles
Brain stem reticular formation
ANS function, sleep-wake cycles
Pineal gland Melatonin
Melatonin
Activation of MT1 receptors is the likely mechanism of how melatonin regulates sleep2
Activation of MT2 receptors is the likely mechanism of how melatonin influences circadian rhythm phase shifts2
Adapted from: http://www.brightenyourlife.info/images/slide4.jpg
Phase Response Curve
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Jet-Lag SWSD 1o Insomnia DSPSDose 0.5-8mg on
arrival day, continue for 2-5
days
2-12mg for up to 4 weeks
2-3mg prior to bedtime for up
to 29 weeks
5mg prior to bedtime for up
to 1 week
0.3-5mg for up to 9 months
Formulation IR IR, CR, FR, SR CR, FR, SR IRROA PO PO PO PO
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Design N patients Intervention ResultsRandomized, double-blind,
placebo-controlled crossover trial
22 Melatonin or placebo 5mg PO QD x 4 weeks between 1900 and2100 hours, 1 week washout period, received other treatment x 4 additional weeks
20/22 patients finished the study àsleep onset latency was significantly reduced while subject were taking melatonin as compared with both placebo and baseline
Strengths Limitations Conclusion
• No ADEs noted• Study design allowed
patients to select their baseline bedtime and duration of sleep àpermitting investigators the ability to compare their natural sleep pattern with that of the imposed sleep period (2400 to 0800 hours)
• No evidence that melatonin altered total sleep time
• Melatonin did alter subjective measures of sleepiness, fatigue or alertness
• Small sample size• Crossover design – each
patient served as his or her own control
• Not well controlled• Dose response relationships,
possibility of relapse after discontinuation, not explored
• Melatonin 5mg 3-4 hours prior to bedtime was an effective treatment for patients with DSPS
Design N trials ResultsCochrane Systematic
Review10 8/10 trials found that
melatonin, taken close to the target bedtime at destination time of 2200 –0000 hours, decreased jet-lag from flights crossing 5+ time zones.
Other findings ConclusionDaily doses of melatonin ranging from 0.5-5mg were shown to be similarly effective; however, patients fell asleep faster and better after 5mg vs. 0.5mg
2mg slow-release melatonin suggested a relative ineffective short-lived higher peak concentration vs. 0.5-5mg (NNT = 2)
Start taking two nights prior to flight and continue for 4 nights after arrival
Reports suggested that patients with epilepsy, and patients taking warfarin may be harmed by concurrent administration with melatonin
Melatonin was remarkable effective in preventing jet lag
Safety and efficacy was proven for occasional short-term use
Should be recommended to adult travelers flying across 5+ time zones, particularly on an eastward flight
Design N patients InterventionRandomized, double-blind,
placebo-controlled crossover trial
10 Random order of 0.3mg, 1.0mg melatonin or placebo 60 minutes prior to bedtime for 7 days.
Study was setup for patient to receive each intervention dose with a 5-day washout period in between
After each 7 day treatment, nighttime EEG records were collected
ResultsTreatment; mean (and SD)
Sleep variable Placebo MT 0.3mg MT 1.0mg% waking stage in
total recording time15.7 (15.6) 15.5 (15.9) 17.3 (18.8)
No. of awakenings 6.4 (5.1) 6.5 (4.2) 5.9 (2.4)Total time waking
stage, min73.8 (74.1) 72.1 (76.4) 83.0 (90.7)
There were no significant differences in sleep EEG, the amount or subjective quality of sleep or side effects between the placebo, 0.3-mg melatonin or 1.0-mg melatonin treatments.
Strengths Limitations Conclusion• Exclusion criteria ruled
out confounders at baseline (e.g., all other sleep disorder diagnoses were excluded)
• Small sample size• Findings are difficult to
interpret because of the variability of the same (e.g., age)
• Crossover study – each patient served as his or her own control
• Melatonin did not produce any sleep benefit in this sample of patients with primary insomnia
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