Effects of exogenous melatonin on sleep: A meta-analysis. Sleep Med Rev 9: 41-50

Department of Obstetrics and Gynecology, Hadassah Medical Center, Jerusalem, Israel.
Sleep Medicine Reviews (Impact Factor: 8.51). 03/2005; 9(1):41-50. DOI: 10.1016/j.smrv.2004.06.004
Source: PubMed


Exogenous melatonin reportedly induces drowsiness and sleep, and may ameliorate sleep disturbances, including the nocturnal awakenings associated with old age. However, existing studies on the soporific efficacy of melatonin have been highly heterogeneous in regard to inclusion and exclusion criteria, measures to evaluate insomnia, doses of the medication, and routes of administration. We reviewed and analyzed (by meta-analysis) available information on effects of exogenous melatonin on sleep. A MEDLINE search (1980 to December 2003) provided English-language articles, supplemented by personal files maintained by the authors. The analysis used information derived from 17 different studies (involving 284 subjects) that satisfied inclusion criteria. Sleep onset latency, total sleep duration, and sleep efficiency were selected as the outcome measures. The study effect size was taken to be the difference between the response on placebo and the mean response on melatonin for each outcome measured. Melatonin treatment significantly reduced sleep onset latency by 4.0 min (95% CI 2.5, 5.4); increased sleep efficiency by 2.2% (95% CI 0.2, 4.2), and increased total sleep duration by 12.8 min (95% CI 2.9, 22.8). Since 15 of the 17 studies enrolled healthy subjects or people with no relevant medical condition other than insomnia, the analysis was also done including only these 15 studies. The sleep onset results were changed to 3.9 min (95% CI (2.5, 5.4)); sleep efficiency increased to 3.1% (95% CI (0.7, 5.5)); sleep duration increased to 13.7 min (95% CI (3.1, 24.3)).

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    • "Moreover the optimal dose of MLT is not defined and is consensual (Gitto et al., 2011). After an oral administration of a fast-release dosage form, the peak concentration is reached on average within 60 min (Brezezinski et al., 2005) as MLT is hepatically metabolized, with 80–90% converted to 6-sulphatox- ymelatonin, an inactive compound excreted in the urine. Dietary supplements with prolonged MLT release are now available in the market. "

    International Journal of Pharmaceutics 07/2014; 469(1):67–79. · 3.65 Impact Factor
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    • "Melatonin is a hormone primarily produced by the pineal gland in all vertebrates, and its secretion follows a circadian pattern. Melatonin is known for its sleep-promoting effects, which include shortening of sleep latency and lengthening of sleep duration (Brzezinski et al. 2005). In addition, evidence from both experimental and clinical studies has shown that melatonin also plays an important role in pain regulation (Mickle et al. 2010; Wilhelmsen et al. 2011). "
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    ABSTRACT: An effective and safe treatment of insomnia in patients with neuropathic pain remains an unmet need. Melatonin and its analogs have been shown to have both analgesic and hypnotic effects; however, capacity of them on sleep disturbance with neuropathic pain as well as the precise mechanism is unclear. The present study evaluated effects of piromelatine, a novel melatonin receptor agonist, on sleep disturbance in a neuropathic pain-like condition as well as the underlying mechanisms. A mouse model of chronic neuropathic pain induced by partial sciatic nerve ligation (PSL) was employed. The antinociceptive and hypnotic effects of piromelatine were evaluated by measurement of thermal hyperalgesia, mechanical allodynia, and electroencephalogram (EEG) recordings in PSL mice. Pharmacological approaches were used to clarify the mechanisms of action of piromelatine. PSL significantly lowered thermal and mechanical latencies and decreased non-rapid eye movement (NREM) sleep, and PSL mice exhibited sleep fragmentation. Treatment with 25, 50, or 100 mg/kg of piromelatine significantly prolonged thermal and mechanical latencies and increased NREM sleep. Moreover, the antinociceptive effect of piromelatine was prevented by melatonin antagonist luzindole, opioid receptor antagonist naloxone, or 5HT1A receptor antagonist WAY-100635. The hypnotic effect of piromelatine was blocked by luzindole but neither by naloxone nor WAY-100635. These data indicate that piromelatine is an effective treatment for both neuropathic pain and sleep disturbance in PSL mice. The antinociceptive effect of piromelatine is likely mediated by melatonin, opioid, and 5HT1A receptors; however, the hypnotic effect of piromelatine appears to be mediated by melatonin receptors.
    Psychopharmacology 04/2014; 231(20). DOI:10.1007/s00213-014-3530-5 · 3.88 Impact Factor
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    • "Many studies of melatonin both in vitro and in animal models show that melatonin is a powerful free radical scavenger [2], indirect antioxidant [3] and provides cytoprotection [4]. These properties lead to the use and study of melatonin in various diseases, especially cancer, sleep disorders [5] and jet lag [6]. Melatonin pharmacokinetics show low bioavailability (15%) in the bloodstream after oral administration. "
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    ABSTRACT: The pharmacokinetic study of melatonin uptake requires a validated bioanalytical method for analysis. This study developed and validated a method for determination of melatonin in human plasma by high-performance liquid chromatography (HPLC)-fluorescence detector. Human plasma (100 uL) was extracted by liquid-phase extraction using dichloromethane (500 μL). An internal standard (N-acetylserotonin) was also used. After shaking, equilibration, separation of the layers and dying under nitrogen gas, the residue was redissolved in 50 μL of 100% acetonitrile and 40 μL of sample was injected into a 20 μL loop of the HPLC system. Separation was carried out on a HiQ Sil C18V column (5 μm, 250 mm x 4.6 mm) with 25% acetonitrile/phosphate buffer, pH 7.0 with a flow rate of 1.0 mL/min. Fluorescence excitation and emission wavelengths were set to 286 nm and 346 nm, respectively. Retention time of N-acetylserotonin and melatonin standard were approximately 5 and 9 minutes, respectively. The coefficient of variation (CV) of retention time was 0.4% with no interferences from other endogenous species. Linearity of melatonin standard was 0.9998, %CV of precision was 3.7%, and recovery was 96.3 to 101.5% with %CV 5.2–6.7% over a range of 7.2–180 ng/mL. Inter-day and inter-day precision were 4.8% and 5.9%, respectively. The limit of detection was 3 ng/mL and limit of quantification was 10 ng/mL. The method will be applied to pharmacokinetics study of novel melatonin delivery formulations using rats.
    2nd International Conference on Applied Science (ICAS), Souphanouvong University, Luang Prabang, Lao PDR; 03/2011
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