Melatonin not working
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Melatonin Not Working: Insights from Recent Research
Melatonin and Sleep Disorders: Efficacy and Limitations
Melatonin, a hormone produced by the pineal gland, is widely recognized for its role in regulating sleep and circadian rhythms. Despite its popularity, recent studies have shown mixed results regarding its effectiveness in treating various sleep disorders.
Primary Sleep Disorders
Research indicates that melatonin can be effective in reducing sleep onset latency in individuals with primary insomnia and delayed sleep phase syndrome. A meta-analysis of randomized controlled trials found significant improvements in sleep onset latency for these conditions, suggesting that melatonin can help individuals fall asleep faster2. However, the evidence is less clear for other sleep disorders, such as non-24-hour sleep-wake syndrome in blind individuals and rapid eye movement behavior disorder, where the results are more variable2.
Extended-Release vs. Immediate-Release Melatonin
The formulation of melatonin also plays a crucial role in its effectiveness. Immediate-release melatonin has shown inconsistent results in treating insomnia, whereas prolonged-release formulations like Circadin® have demonstrated more reliable improvements in sleep quality, sleep latency, and next-day alertness, particularly in older adults8. This suggests that the timing and duration of melatonin release are critical factors in its efficacy.
Melatonin and Delirium in Hospitalized Patients
The use of melatonin to prevent delirium in hospitalized patients has been explored, but the findings are inconclusive. A meta-analysis of 16 trials involving 1634 patients found no significant reduction in the incidence of delirium with melatonin use. However, it did show a significant reduction in the length of stay in intensive care units1. The high heterogeneity and low certainty of evidence across these trials highlight the need for more robust, multi-center studies to determine melatonin's role in delirium prevention.
Neuroprotective Properties of Melatonin
Beyond sleep regulation, melatonin has been studied for its neuroprotective properties. In animal models, melatonin has shown potential in protecting against oxidative stress and neurogenesis impairment caused by treatments like 5-fluorouracil (5-FU). Melatonin administration in rats reduced oxidative stress markers and improved antioxidant enzyme levels in the hippocampus and prefrontal cortex, suggesting a protective effect on brain health3.
Traumatic Brain Injury (TBI)
Melatonin's neuroprotective effects have also been evaluated in the context of traumatic brain injury (TBI). Preclinical studies indicate that melatonin can mitigate the effects of TBI through various mechanisms, including reducing oxidative stress and inflammation. However, most studies have been conducted on adult male rats, and there is a need for more diverse and long-term studies to fully understand its potential benefits4.
Circadian Rhythm Dysregulation
Circadian rhythm disorders, such as those caused by shift work or jet lag, can also benefit from melatonin treatment. Melatonin helps realign the circadian clock by signaling the onset of night, thereby improving sleep quality and reducing the symptoms of circadian misalignment5 7. However, the clinical application of melatonin in these contexts requires further investigation to optimize dosing and timing.
Conclusion
While melatonin shows promise in treating certain sleep disorders and providing neuroprotective benefits, its effectiveness can vary based on the condition being treated, the formulation used, and individual patient factors. The current body of research highlights the need for more comprehensive and well-designed studies to fully understand the therapeutic potential and limitations of melatonin. For individuals finding melatonin ineffective, consulting with a healthcare provider to explore alternative treatments or adjust dosing strategies may be beneficial.
Sources and full results
Most relevant research papers on this topic
The effect of melatonin on delirium in hospitalised patients: A systematic review and meta-analyses with trial sequential analysis.
Melatonin's effect on preventing delirium in hospitalized patients remains inconclusive, but may shorten intensive care unit stays.
Meta-AnalysisEvidence for the efficacy of melatonin in the treatment of primary adult sleep disorders.
Exogenous melatonin shows promising evidence in reducing sleep onset latency in primary insomnia, delayed sleep phase syndrome, and regulating sleep-wake patterns in blind patients compared to placebo.
Meta-Analysis
Highly CitedMelatonin Protects against the Side-Effects of 5-Fluorouracil on Hippocampal Neurogenesis and Ameliorates Antioxidant Activity in an Adult Rat Hippocampus and Prefrontal Cortex
Melatonin protects against 5-fluorouracil-induced neurogenesis and oxidative stress in the hippocampus and prefrontal cortex, restoring antioxidant enzyme levels and reducing oxidative stress.
RCT
Animal Study
Rigorous JournalMelatonin as a Therapy for Traumatic Brain Injury: A Review of Published Evidence
Melatonin shows neuroprotective properties and low toxicity after traumatic brain injury, but more long-term studies are needed.
Systematic ReviewCircadian Rhythm Dysregulation and Restoration: The Role of Melatonin
Melatonin dysregulation contributes to sleep and circadian disorders, but its potential therapeutic use has not been widely studied in clinical studies.
Systematic Review
Very Rigorous JournalHighly CitedMelatonin as a Hormone: New Physiological and Clinical Insights.
Melatonin plays a crucial role in coordinating behavioral and physiological adaptations to environmental light/dark cycles and seasons, and its therapeutic use is based on its unique biological time-domain-acting properties.
Highly CitedNew perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation
Melatonin treatment can improve sleep quality, promote healthy aging, and potentially prevent Alzheimer's disease by regulating circadian rhythms and regulating sleep-wake cycles.
Rigorous JournalHighly Cited[Melatonin: Physiological and pharmacological aspects related to sleep: The interest of a prolonged-release formulation (Circadin®) in insomnia].
Circadin®, a prolonged-release melatonin preparation, can improve sleep quality and life quality in insomnia patients aged 55 years and older without rebound effects or safety concerns.
Literature ReviewCurrent role of melatonin in pediatric neurology: clinical recommendations.
Melatonin is effective in treating sleep onset insomnia and delayed sleep phase syndrome in children with developmental disorders, and may help reduce seizures and headaches.
Non-RCTHighly CitedMelatonin, energy metabolism, and obesity: a review
Melatonin replacement therapy may help restore a more healthy balance in energy metabolism and circadian rhythms, potentially contributing to weight loss and improved health.
Literature ReviewHighly Cited