Effectiveness of Exogenous Melatonin in Insomnia

Effectiveness of Exogenous Melatonin in InsomniaWOO YUN KINCHAPTER 1INTRODUCTION investigate contextSleep is not always a luxury. Insomnia is defined as a pile throw out of kilter in which in that respect is an inability to fall a quietus or stay a calm as long as desired (Roth T. 2007). It is estimated that up to 34% of adults in the United States and 37% in Europe have most forms of insomnia (Leger D. 2005). Insomnia can be classified to mild, moderate and severe fit in to the International Classification of Sleep Disorder (ICSD).Melatonin (5-methoxy-N-acetyltryptamine) is a lipid soluble hormone secreted by the pineal gland during hours of darkness. Melatonin has several physiological functions including regulation of the circadian rhythms, modulation of annealal change and a powerful antioxidant (Gitto et al. 2013). With age, it has been shown that the 24hour melatonin secretion is significantly reduced and so affecting the normal circadian pedal (Iguchi et al. 1982).At present, insomnia is typically treated symptomatically, often with benzodiazepine or antidepressants. However chronic insomnia requires long condition discourse which whitethorn cause significant side make and unwanted drug-drug interaction. Approximately 29-61% of older adults with insomnia complaints have preexisting recreation apnea (Krakow et al. 2001). With the combination of insomnia and sleep apnea, sedative-hypnotic treatments may incense the sleep apnea (Mendelson et al. 1981).Exogenous melatonin is a chronobiotic drug with some hypnotic properties (Zhdanova et al. 1997), it has become of the most frequently non-prescribed sleep aid collectable to its role in regularisation and promoting sleep (Wagner et al. 1998). some studies have shown that supplemental melatonin can increase sleep propensity, although it may not be as effective as prescribed sleep medication (Zhdanova I. 2005).Problem StatementSleep adequacy complicates, property, timing and also duration. It has been estimated that the direct health cost of sleep disorder amounts to $1144 million Australian dollars in 2001 (NHS Aus. 2001), and 7.6% of the total motor vehicle accidents(MVA) in 2004 are indirectly cause by sleep disorders amounting to $808million net health costs. Studies have been done to show the benefits of exogenous melatonin for sleep disorders on individuals with intellectual disabilities and adolescence however very little has been done to show its effectiveness on the ecumenic population. Malaysia, has one of the highest rate of MVA in the world where according to Malaysian Institute of Road Safety (MIROS), from 1997 to 2007, there has been an increase of 59% of MVA and the main reason identified was driving fatigue due to awkward operative hours/shift works (Kee et al. 2010). Availability of exogenous in Malaysia is scarce and it is not fully understood.Research QuestionHow effective is exogenous melatonin in treating insomnia in general population?How safe is exogenous melatonin?Research ObjectiveTo review efficacy of exogenous melatonin in treating insomniaTo access the safety of exogenous melatoninSignificance of Research information from available clinical trials and studies done on the efficacy of exogenous melatonin in insomnia will be compiled and compared to enable a more comprehensive and easily social result database. With the comprehensive database, clinicians will have a better understanding on the efficacy of MSCs and the best treatment option for the patient, thus improving patients quality of life.CHAPTER 2LITERATURE REVIEW2.1 INSOMNIAInsomnia is often defined by the presence of an individuals report of difficulty with sleep (Roth T 2007). The criteria often employ in diagnosing insomnia includes i)difficulty falling asleep, staying asleep or nonrestorative sleep, ii) this opportunity is present despite adequate opportunity and circumstance to sleep, iii) this impairment in sleep is associated with sidereal day impairmen t or distress and iv) this sleep difficulty occurs at least 3 times per week and has been a problem for the past 1 calendar month (Roth T 2007). The pathophysiology of insomnia can be due to the disorder of the hyper-arousal state throughout the whole day which causes alertness during the day and difficulty in falling or maintaining sleep (Stepanski E, 1988). A cross sectional turn over done on 156 US air force personal found that 40% suffered from sleep disorder and 75% reported diminished sleep quality while deployed overseas (Peterson AL, 2008). A study done in 2013 (Lentino et al, 2013) showed that 25% of the 14148 army and national harbor personal reported to be poor sleepers thus affecting the quality of sleep and the quality of service.2.2 CURRENT TREATMENT FOR INSOMNIACurrently the medications used for treating insomnias and other sleep disorders includes benzodiazepine receptor agonist (eg. Zolpidem, zipoclone) which are only limited to short term use (4 weeks) (Sanofi Av entis, 2007). The medication large affects the brain through the GABA receptors and long term use has been associated with memory and balance impairment, rebound imsomnia, withdrawal symptoms and abuse potential (Rush CR, 1999). Recent short termed studies have shown that discontinuation of the benzodiazepines lead to disruption of the sleep computer architecture and also increases sleep latency which makes withdrawing from treatment difficult (Mann K, 1996).2.3 MELATONINMelatonin (5-methoxy-N-acetyltryptamine) is a lipid soluble hormone that is shown to be involved with the sleep physiology (Dijk D-J, 1997).it is also regulates the modulation of season change, in reproduction, antioxidant, oncostatic, anti inflammatory and anti-convulsant effect (Gitto E, 2013). Melatonin is mostly produced in the pineal gland in the brain during the hours of darkness and is involved in the regulation of the sleep-wake cycle (circadian cycle).the circadian process is maintained by the suprachiasmat ic nucleus (SCN) which contains high number of melatonin receptors. During daytime, the SCN produces an arousal signal that maintains the wakefulness and prevents sleep drive however in darkness, there is a feedback loop which causes the release of melatonin which feeds back and inhibits the SCN (Geert et al, 2009) It has been documented that melatonin decreases with age especially in post menopausal women (Okatani Y, 2000). Other than to promote sleep, melatonin also shows sedative and anti-excitory effects (Hardeland R, 2008).2.4 EXOGENOUS MELATONINExogenous melatonin has become one of the most frequently prescribed over the counter drug for those looking for non-prescription sleep medication (Wagner J, 1998). The exogenous melatonin is marketed to athletic supporter promote quality sleep, helps in jet lag, or to regulate the circadian cycle due to jet lag or shift work due to its regulator role in the internal timing of biological rhythm. Some studies have shown that exogenous m elatonin can help increase the sleep propensity although it may not be as effective as prescribed sleep medications (Zhdanova I, 2005). Studies have also been done regarding the use of exogenous melatonin in the treatment of sleep problems in individuals with sleep disability (Turk 2003) however there are still doubts on the efficacy of exogenous melatonin usage for the general public.CHAPTER 3METHODOLOGY3.1 Research DesignThis research was based on the PICOS guidelines Population (P) All types of insomnia patientsIntervention (I) Exogenous melatoninComparitor (C) Insomnia patients on treatment with exogenous melatonincompared with other treatment by questionnaires expiration (O) Efficacy and safety of treatmentStudy design (S) Randomized Controlled trials (RCT), Surveys3.2 DatabaseLiterature search was done on electronic articles/ journals in Central, PubMed and Google Scholar.3.3 KeywordsKey words used to search articles with MESH terms wereInsomniaExogenous melatonin3.4 Quality A ssessmentQuality assessment of the paper was done using Jadad scoring for randomized controlled trials (RCT) and new-fashionedcastle-Ottawa Scale (NOS) for case-control and age group studies.1.Jaded score assesses the quality of published clinical trials based on methods relevant to random assignment, double blinding and the flow of patients. There are 7 criteria evaluated, whereby 1 point is given if the criteria is met and the last 2 crietria carries a negative mark. Range of score is from 0 (bad) to 5 (good) (Jadad et al. 1996).i. Was the study described as randomized (this include words such as randomly, random, and randomization)? +1 pointii. Was the method used to generate the sequence of randomization described and appropriate (table of random numbers, computer generated etc)? +1 pointiii. Was the study described as double blind? +1 pointiv. Was the method of double blinding described and appropriate (identical placebo, active placebo, dummy, etc)? +1 pointv. Was there a r endering of withdrawals and dropouts? +1pointvi. work out one point if the method used to generate the sequence of randomization was described and it was inappropriate (patients were allocated alternately, or according to date of birth, hospital number, etc)?vii. Deduct one point if the study was described as double blind but the method of blinding was inappropriate (eg. comparison of table vs. injection with no double dummy)2. Newcastle-Ottawa Scale (NOS) is developed to assess the quality of the non-randomized studies with its design, content and ease of use directed to the purpose of incorporating the quality assessments in the interpretation of the results. A wiz system is developed to judge on 3 broad perspectives (Wells et al. 2014)i. The selection of the study groupsii. The comparability of the groupsThe ascertainment of either the exposure or outcome of interest for case-control or cohort studies respectively3.5 Inclusion and Exclusion CriteriaInclusion criteriaStudies inc luded in this review were chosen according to the flowing criteria i. Papers published in face language (2010-2015)ii. All study designs were included to maximize the data collectionStudy subjects includes all types of insomnia patientsExclusion criteriaStudies that were done in foreign language and brute studies were excluded in this review3.6 Ethical ClearanceThe ethical committee of UCSI was notified regarding this thesis write-up3.7 GAANT Chart3.8 MilestoneProposal presentation 27.02.2015Submission 31.03.2015Data analysis contend 30.05.2015Thesis submission 15.07.2015REFERENCES1. CATHERINE CORNU, L. R., FLORENCE NOEL-BARON, ALAIN NICOLAS, NATHALIE FEUGIER-FAVIER, PASCAL ROY, BRUNO CLAUSTRAT, M. S.-E. A. B. K. 2010. A dietary supplement to improve the quality of sleep a randomized placebo controlled trial. BMC Complementary and Alternative Medicine, 10.2. SZESEEN KEE, S. B. M. T., YONGMENG GOH 2010. Driving fag and Performance among Occupational Drivers in Simulated Prolonge d Driving. Global Journal of Health Science, 2.3. REBECCA B COSTELLO, C. V. 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