Effectiveness of Exogenous Melatonin in Insomnia

Effectiveness of exogenic Melatonin in InsomniaWOO YUN kindCHAPTER 1INTRODUCTION explore BackgroundSleep is not ceaselessly a luxury. Insomnia is defined as a rest sickness in which at that place is an inability to fall slumberous 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 chip in some forms of insomnia (Leger D. 2005). Insomnia fuel be classified to mild, moderate and severe according to the International miscellanea 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, intonation of seasonal change and a powerful antioxidant (Gitto et al. 2013). With age, it has been re getn that the 24hour melatonin secretion is significantly trim back thus affecting the normal circadian circle (Iguchi et al. 1982) .At present, insomnia is typically treated symptomatically, often with benzodiazepine or antidepressants. However continuing insomnia requires long border manipulation which may ca design significant side effects and outcast dose-drug interaction. Approximately 29-61% of quondam(a) adults with insomnia complaints have preexisting tranquillity apnea (Krakow et al. 2001). With the combination of insomnia and peacefulness apnea, sedative-hypnotic treatments may worsen the remainder 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- dictate pause abet callable to its role in regulating and promoting sleep (Wagner et al. 1998). some studies have shown that supplemental melatonin can augment sleep appositeness, although it may not be as effective as prescribed sleep medication (Zhdanova I. 2005). chore StatementSleep adequacy includes, tone, timing and in a ny case 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 aggregate motor vehicle accidents(MVA) in 2004 are indirectly ca apply by sleep disorders amounting to $808million net health costs. Studies have been make to show the benefits of exogenic melatonin for sleep disorders on various(prenominal)s with intellectual disabilities and adolescence however very little has been do to show its effectiveness on the full general population. Malaysia, has one of the highest rate of MVA in the serviceman 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 overdue to awkward dressing 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 qualification of exogenous melatonin in treating insomniaTo access the safety of exogenous melatoninSignificance of ResearchData from available clinical trials and studies done on the efficacy of exogenous melatonin in insomnia will be compiled and compared to enable a more blanket(prenominal) and easily accessible result entropybase. 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 clog 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 i mpairment in sleep is associated with daytime impairment or distress and iv) this sleep difficulty occurs at least 3 times per week and has been a problem for the last(prenominal) 1 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 sectioned analyze done on 156 US air force personal found that 40% suffered from sleep disorder and 75% describe superfluous sleep quality while deployed overseas (Peterson AL, 2008). A development done in 2013 (Lentino et al, 2013) showed that 25% of the 14148 army and national guard 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 sensory receptor agonist (eg. Zolpidem , zipoclone) which are only limited to short edge use (4 weeks) (Sanofi Aventis, 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 effectiveness (Rush CR, 1999). Recent short termed studies have shown that discontinuation of the benzodiazepines lead to interruption of the sleep 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 mingled 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 by and large 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 suprachiasmatic 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 stretch out 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 gain ground 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 foreclose drug for those looking for non-prescription sleep medication (Wagner J, 1998). The exogenous melatonin is marketed to help 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. about studies have shown that exogenous melatonin 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 questionnairesOutcome (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 engagement terms wereInsomniaExogenous melatonin3.4 Quality AssessmentQuality assessment of the radical was done using Jadad scoring for randomise controlled trials (RCT) and Newcastle-Ottawa scale (NOS) for case-control and cohort studies.1.Jaded target assesses the quality of published clinical trials based on manners relevant to random assignment, double eye-popping 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. mark of score is from 0 (bad) to 5 (good) (Jadad et al. 1996).i. Was the study described as randomize (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, electronic 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 description of withdrawals and dropouts? +1pointvi. Deduct 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 say to the purpose of incorporating the quality assessments in the interpretation of the results. A star schema 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 included in this review were chosen according to the flowing criteria i. Papers published in English 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 unlike language and animal 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 27.02.2015 calmness 31.03.2015Data analysis complete 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 Fatigue and Performance among Occupational Drivers in Simulated Prolonged Driving. Global ledger of Health Science, 2.3. REBECCA B COSTELLO, C. V. 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