PMID 11279722 Melatonin for preventing and treating jet lag 체계적 문헌고찰(코크란) · Cochrane Database Syst Rev, 2002 10개 RCT 중 9건 - 목적지 취침시각 무렵 복용한 멜라토닌이 5+ 시간대 비행 시차증을 줄임(NNT 2). '놀랄 만큼 효과적', 짧게 쓰면 안전. 0.5~5 mg, 타이밍이 관건.
핵심요약
시차증 예방·완화를 위한 경구 멜라토닌을 본 코크란치료·예방의 근거를 엄격히 검토·종합하는 국제 연구 네트워크(Cochrane). 체계적 문헌고찰. 포함 기준을 만족한 무작위 시험 10건 중 9건에서, 목적지 취침시각(밤 10시~자정)에 가깝게 복용한 멜라토닌이 5개 이상 시간대를 건넌 비행의 시차증을 줄였다. 하루 0.5~5 mg이 비슷하게 효과적이었고(5 mg에서 더 빨리·잘 잠), 5 mg 초과는 추가 이득이 없었으며, 2 mg 서방형성분이 몸에서 천천히 오래 방출되도록 만든 제형(서방정, prolonged-release).이 상대적으로 덜 효과적인 점은 짧고 높은 혈중 최고농도가 더 낫다는 것을 시사한다. NNT는 2. 건넌 시간대가 많을수록·동쪽일수록 이득이 크고, 잘못된 시각(이른 낮)에 복용하면 오히려 적응을 늦춘다. 저자들은 멜라토닌이 시차증에 놀랄 만큼 효과적이고 짧게 쓰면 안전해 보인다고 결론지으며, 뇌전증·와파린 복용자 주의와 제품 품질관리 필요성을 덧붙였다.
원문 초록 보기
BACKGROUND: Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. OBJECTIVES: To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. SELECTION CRITERIA: Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. DATA COLLECTION AND ANALYSIS: Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. MAIN RESULTS: Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. Based on the review, the number needed to treat (NNT) is 2. The benefit is likely to be greater the more time zones are crossed, and less for westward flights. The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low. Case reports suggest that people with epilepsy, and patients taking warfarin may come to harm from melatonin. REVIEWER'S CONCLUSIONS: Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It should be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation. ※ 파이프라인이 API로 수집·저장한 초록 원문 그대로. 한국어 핵심요약은 이 텍스트만을 근거로 작성됩니다.
원문 보기 ↗ PMID 21120122 The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis 메타분석 · Sleep, 2010 성인 91·소아 226명 - 멜라토닌이 내인 멜라토닌 분비 시각 1.18h·잠드는 시각 0.67h 앞당기고 수면잠복기잠자리에 든 뒤 실제로 잠들기까지 걸리는 시간. 짧을수록 빨리 잠든다. 23분↓; 단 기상·총수면시간은 불변(리듬 이동제).
핵심요약
지연성 수면위상장애잠드는 시각과 깨는 시각이 사회적 기준보다 크게 뒤로 밀린 일주기 리듬 장애(DSWPD).에서 외인성 멜라토닌의 효과·안전을 본 메타분석여러 개별 연구의 결과를 통계적으로 합쳐 하나의 종합 결론을 내는 분석.. 성인 91명이 포함된 5건, 소아 226명이 포함된 4건의 무작위 시험을 종합한 결과, 멜라토닌은 몸이 스스로 멜라토닌을 내보내기 시작하는 시각을 평균 1.18시간(95% CI 0.89~1.48), 실제 잠드는 시각을 0.67시간(0.45~0.89) 앞당겼고, 수면잠복기잠자리에 든 뒤 실제로 잠들기까지 걸리는 시간. 짧을수록 빨리 잠든다.를 23.27분(4.83~41.72) 줄였다. 반면 기상 시각과 총 수면시간은 유의하게 변하지 않았다. 저자들은 멜라토닌이 지연성 수면위상장애에서 수면-각성 리듬과 내인 멜라토닌 리듬을 앞당기는 데 효과적이라고 결론지었다. 총 수면량이 아니라 '리듬의 위치'를 바꾸는 성분임을 보여준다.
원문 초록 보기
STUDY OBJECTIVES: To perform a meta-analysis of the efficacy and safety of exogenous melatonin in advancing sleep-wake rhythm in patients with delayed sleep phase disorder. DESIGN: Meta analysis of papers indexed for PubMed, Embase, and the abstracts of sleep and chronobiologic societies (1990-2009). PATIENTS: Individuals with delayed sleep phase disorder. INTERVENTIONS: Administration of melatonin. MEASUREMENTS AND RESULTS: A meta-analysis of data of randomized controlled trials involving individuals with delayed sleep phase disorder that were published in English, compared melatonin with placebo, and reported 1 or more of the following: endogenous melatonin onset, clock hour of sleep onset, wake-up time, sleep-onset latency, and total sleep time. The 5 trials including 91 adults and 4 trials including 226 children showed that melatonin treatment advanced mean endogenous melatonin onset by 1.18 hours (95% confidence interval [CI]: 0.89-1.48 h) and clock hour of sleep onset by 0.67 hours (95% CI: 0.45-0.89 h). Melatonin decreased sleep-onset latency by 23.27 minutes (95% CI: 4.83-41.72 min). The wake-up time and total sleep time did not change significantly. CONCLUSIONS: Melatonin is effective in advancing sleep-wake rhythm and endogenous melatonin rhythm in delayed sleep phase disorder. ※ 파이프라인이 API로 수집·저장한 초록 원문 그대로. 한국어 핵심요약은 이 텍스트만을 근거로 작성됩니다.
원문 보기 ↗ PMID 23691095 Meta-analysis: melatonin for the treatment of primary sleep disorders 메타분석 · PLoS One, 2013 19개 RCT·1,683명 - 멜라토닌이 수면잠복기잠자리에 든 뒤 실제로 잠들기까지 걸리는 시간. 짧을수록 빨리 잠든다. 7.06분↓·총수면 8.25분↑·수면질 SMD 0.22 개선; 효과는 '완만'하고 다른 불면약보다 절대 이득 작음.
핵심요약
일차성 수면장애 환자에서 멜라토닌 대 위약유효 성분이 없는 가짜 약(플라시보). 효과 비교의 기준으로 쓴다.의 효과를 본 메타분석여러 개별 연구의 결과를 통계적으로 합쳐 하나의 종합 결론을 내는 분석.(성인·소아). 무작위 위약대조 시험 19건·1,683명을 종합한 결과, 멜라토닌은 수면잠복기잠자리에 든 뒤 실제로 잠들기까지 걸리는 시간. 짧을수록 빨리 잠든다.를 7.06분(95% CI 4.37~9.75) 줄이고 총 수면시간을 8.25분(1.74~14.75) 늘렸으며, 전반적 수면의 질을 표준화 평균차 0.22(0.12~0.32)만큼 유의하게 높였다. 용량·기간이 길수록 수면잠복기·총수면 효과가 컸다. 저자들은 멜라토닌의 수면 효과가 '완만하지만' 계속 써도 사라지지 않으며, 위약 대비 절대적 이득은 다른 불면증 약보다 작으나 부작용이 상대적으로 적어 불면증에서 쓸 자리가 있을 수 있다고 결론지었다.
원문 초록 보기
STUDY OBJECTIVES: To investigate the efficacy of melatonin compared to placebo in improving sleep parameters in patients with primary sleep disorders. DESIGN: PubMed was searched for randomized, placebo-controlled trials examining the effects of melatonin for the treatment of primary sleep disorders. Primary outcomes examined were improvement in sleep latency, sleep quality and total sleep time. Meta-regression was performed to examine the influence of dose and duration of melatonin on reported efficacy. PARTICIPANTS: Adults and children diagnosed with primary sleep disorders. INTERVENTIONS: Melatonin compared to placebo. RESULTS: Nineteen studies involving 1683 subjects were included in this meta-analysis. Melatonin demonstrated significant efficacy in reducing sleep latency (weighted mean difference (WMD) = 7.06 minutes [95% CI 4.37 to 9.75], Z = 5.15, p<0.001) and increasing total sleep time (WMD = 8.25 minutes [95% CI 1.74 to 14.75], Z = 2.48, p = 0.013). Trials with longer duration and using higher doses of melatonin demonstrated greater effects on decreasing sleep latency and increasing total sleep time. Overall sleep quality was significantly improved in subjects taking melatonin (standardized mean difference = 0.22 [95% CI: 0.12 to 0.32], Z = 4.52, p<0.001) compared to placebo. No significant effects of trial duration and melatonin dose were observed on sleep quality. CONCLUSION: This meta-analysis demonstrates that melatonin decreases sleep onset latency, increases total sleep time and improves overall sleep quality. The effects of melatonin on sleep are modest but do not appear to dissipate with continued melatonin use. Although the absolute benefit of melatonin compared to placebo is smaller than other pharmacological treatments for insomnia, melatonin may have a role in the treatment of insomnia given its relatively benign side-effect profile compared to these agents. ※ 파이프라인이 API로 수집·저장한 초록 원문 그대로. 한국어 핵심요약은 이 텍스트만을 근거로 작성됩니다.
원문 보기 ↗ PMID 29096777 Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children With Autism Spectrum Disorder 무작위 대조시험 · J Am Acad Child Adolesc Psychiatry, 2017 자폐 아동 125명·이중맹검 - 서방형성분이 몸에서 천천히 오래 방출되도록 만든 제형(서방정, prolonged-release). 멜라토닌이 야간 총수면 위약유효 성분이 없는 가짜 약(플라시보). 효과 비교의 기준으로 쓴다.보다 +32분(p=.034)·수면잠복기잠자리에 든 뒤 실제로 잠들기까지 걸리는 시간. 짧을수록 빨리 잠든다. -25분(p=.011), 반응자 68.9 vs 39.3%(NNT 3.38). 단 제약사(뉴림) 연구.
핵심요약
행동 개입만으로 수면이 나아지지 않은 자폐 스펙트럼 장애(일부 ADHD·신경유전질환 동반) 아동·청소년 125명(2~17.5세)을 대상으로 소아용 서방형성분이 몸에서 천천히 오래 방출되도록 만든 제형(서방정, prolonged-release). 멜라토닌(PedPRM, 2 mg에서 5 mg 증량) 대 위약유효 성분이 없는 가짜 약(플라시보). 효과 비교의 기준으로 쓴다.을 13주간 비교한 이중맹검 무작위 시험. 주요 지표인 야간 총 수면시간이 멜라토닌군에서 평균 57.5분 늘어 위약(9.14분)보다 유의하게 길었고(보정 차이 -32.43분, p=0.034), 수면잠복기잠자리에 든 뒤 실제로 잠들기까지 걸리는 시간. 짧을수록 빨리 잠든다.도 멜라토닌 39.6분 감소로 위약(12.5분)보다 컸다(보정 차이 -25.30분, p=0.011). 임상적으로 의미 있는 반응자 비율은 68.9% 대 39.3%(NNT 3.38)였고, 졸림이 위약보다 흔했으나 대체로 안전했다. 저자 일부가 제조사(뉴림) 소속이라는 이해상충과 단일 시험이라는 한계가 있다.
원문 초록 보기
OBJECTIVE: To assess the efficacy and safety of novel pediatric-appropriate, prolonged-release melatonin minitablets (PedPRM) versus placebo for insomnia in children and adolescents with autism spectrum disorder (ASD), with or without attention-deficit/hyperactivity disorder (ADHD) comorbidity, and neurogenetic disorders (NGD). METHOD: A total of 125 children and adolescents (2-17.5 years of age; 96.8% ASD, 3.2% Smith-Magenis syndrome [SMS]) whose sleep failed to improve on behavioral intervention alone were randomized (1:1 ratio), double-blind, to receive PedPRM (2 mg escalated to 5 mg) or placebo for 13 weeks. Sleep measures included the validated caregivers' Sleep and Nap Diary (SND) and Composite Sleep Disturbance Index (CSDI). The a priori primary endpoint was SND-reported total sleep time (TST) after 13 weeks of treatment. RESULTS: The study met the primary endpoint: after 13 weeks of double-blind treatment, participants slept on average 57.5 minutes longer at night with PedPRM compared to 9.14 minutes with placebo (adjusted mean treatment difference PedPRM-placebo -32.43 minutes; p = .034). Sleep latency (SL) decreased by 39.6 minutes on average with PedPRM and 12.5 minutes with placebo (adjusted mean treatment difference -25.30 minutes; p = .011) without causing earlier wakeup time. The rate of participants attaining clinically meaningful responses in TST and/or SL was significantly higher with PedPRM than with placebo (68.9% versus 39.3% respectively; p = .001) corresponding to a number needed to treat (NNT) of 3.38. Overall sleep disturbance (CSDI) tended to decrease. PedPRM was generally safe; somnolence was more commonly reported with PedPRM than placebo. CONCLUSION: PedPRM was efficacious and safe for treatment of insomnia in children and adolescents with ASD with/without ADHD and NGD. The acceptability of this pediatric formulation in a population who usually experience significant difficulties in swallowing was remarkably high. ※ 파이프라인이 API로 수집·저장한 초록 원문 그대로. 한국어 핵심요약은 이 텍스트만을 근거로 작성됩니다.
원문 보기 ↗ PMID 27855744 Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content 제품 분석 연구 · J Clin Sleep Med, 2017 시판 30여 종 분석 - 실제 함량 표시량의 -83%~+478%, 71%↑가 ±10% 벗어남; 26%(8종)에서 세로토닌기분·수면 등에 관여하는 신경전달물질. 멜라토닌의 전구물질이며, 일부 보충제에 오염물로 검출됐다. 1~75 µg 검출.
핵심요약
시판 멜라토닌 보충제의 실제 함량과 순도를 정량 분석한 연구. 여러 브랜드·제형의 제품 31종을 초고성능 액체크로마토그래피로 분석한 결과, 멜라토닌 함량이 표시량의 -83%에서 +478%까지 편차를 보였고, 같은 제품의 로트 간 차이도 최대 465%였다. 이 변동은 제조사나 제형과 뚜렷한 상관이 없었다. 또한 8개 제품에서 표시되지 않은 세로토닌기분·수면 등에 관여하는 신경전달물질. 멜라토닌의 전구물질이며, 일부 보충제에 오염물로 검출됐다.이 1~75 µg 검출됐다. 함량이 표시량의 ±10% 안에 든 제품은 29%에 불과(71% 초과가 미달)했고 26%가 세로토닌을 함유했다. 저자들은 수면장애에 쓰는 보충제의 품질을 신뢰할 수 있도록 제조 관리 강화가 필요하다고 결론지었다.
원문 초록 보기
STUDY OBJECTIVES: Melatonin is an important neurohormone, which mediates circadian rhythms and the sleep cycle. As such, it is a popular and readily available supplement for the treatment and prevention of sleep-related disorders including insomnia and jet lag. This study quantified melatonin in 30 commercial supplements, comprising different brands and forms and screened supplements for the presence of serotonin. METHODS: A total of 31 supplements were analyzed by ultraperformance liquid chromatography with electrochemical detection for quantification of melatonin and serotonin. Presence of serotonin was confirmed through analysis by ultraperformance liquid chromatography with mass spectrometry detection. RESULTS: Melatonin content was found to range from -83% to +478% of the labelled content. Additionally, lot-to-lot variable within a particular product varied by as much as 465%. This variability did not appear to be correlated with manufacturer or product type. Furthermore, serotonin (5-hydroxytryptamine), a related indoleamine and controlled substance used in the treatment of several neurological disorders, was identified in eight of the supplements at levels of 1 to 75 μg. CONCLUSIONS: Melatonin content did not meet label within a 10% margin of the label claim in more than 71% of supplements and an additional 26% were found to contain serotonin. It is important that clinicians and patients have confidence in the quality of supplements used in the treatment of sleep disorders. To address this, manufacturers require increased controls to ensure melatonin supplements meet both their label claim, and also are free from contaminants, such as serotonin. ※ 파이프라인이 API로 수집·저장한 초록 원문 그대로. 한국어 핵심요약은 이 텍스트만을 근거로 작성됩니다.
원문 보기 ↗ 