Melatonin In Treatment Research Articles

Мелатонін: роль у патогенезі передчасних пологів та вплив на перинатальні наслідки в передчасно народжених дітей (огляд літератури)

A review of literature on the physiological role and biosynthesis of melatonin, its role in the pathogenesis of premature birth and the impact on perinatal outcomes in premature babies is given. The study of all possible links of the pathogenesis of premature birth remains an urgent issue for scientists all over the world, because despite the amount of information we have today, obstetrician-gynecologists and neonatologists continue the daily struggle with complications for women who have experienced premature birth, as well as for premature babies. Purpose - to investigate the main mechanisms of melatonin’s influence on the course of normal pregnancy and possible complications, such as: premature birth, preeclampsia, fetal growth restriction. Modern researchers are not limited to identifying the pathogenetic aspects of premature birth in which melatonin is involved, therefore the review also includes the main achievements of modern science in the context of the use of exogenous melatonin in the treatment of such life-threatening conditions for prematurely born children as hypoxic-ischemic damage of brain, intraventricular hemorrhages, neonatal sepsis and bronchopulmonary dysplasia. The high safety profile and positive results of experimental studies of melatonin in preterm animals suggest the possibility of using melatonin in antenatal neuroprotection and treatment of postnatal complications, such as hypoxic-ischemic brain damage, neonatal sepsis, and bronchopulmonary dysplasia. No conflict of interests was declared by the authors.

Melatonin improves learning and memory of mice with chronic social isolation stress via an interaction between microglia polarization and BDNF/TrkB/CREB signaling pathway

Chronic social isolation stress (SIS) could impair learning and memory-related behaviors. Herein, we investigated the efficacy of Melatonin in treatment of memory despair and also its possible underlying mechanism of action in an animal model of SIS. For this purpose, mice were allocated to two opposing conditions, including social condition (SC) and isolated condition (IC), for five weeks. The study consisted of three groups, including saline-treated SC, saline-treated IC, Melatonin-treated IC (10 mg/kg/day for five successive days). At the end of the isolation period, mice underwent three neurobehavioral tests: passive avoidance (PA), Morris water maze (MWM), and Y maze (YM) tests. Hippocampus samples were obtained and the expressions of BDNF, TrkB, phosphorylated TrkB (pTrkB), CREB, phosphorylated CREB (pCREB), as well as M1 and M2 microglia were assessed. Interpreting the behavioral tests, we found that isolated mice showed lower freezing response in the PA test, lower number of novel arm visits in the YM, and higher escape latency and less time spent in the target quadrant in the MWM, when compared to SC rodents (P values < 0.001). The isolated group had higher M1/M2 relative ratio (P < 0.001), as well as lower concentrations of BDNF mRNA (p < 0.001) and protein (P < 0.001), TrkB protein (P = 0.035), CREB mRNA (P < 0.001) and protein (P = 0.012), pTrkB (P < 0.001), and pCREB (P = 0.035). However, Melatonin relatively reversed the behavioral, cellular, and molecular effects of SIS. Taken together, melatonin therapy could alleviate memory impairment through switching microglial polarization from M1 to M2 phenotype along with altered expression and function in the BDNF/TrkB/CREB signaling pathway.

Melatonin attenuates chemical-induced cardiotoxicity.

Environmental chemicals and drugs can induce cardiotoxicity, mainly by generating free radicals. Reactive oxygen species play a critical role in the pathogenesis of cardiac tissue injury. This highlights a need for prevention of cardiotoxicity by scavenging free radicals. Melatonin has been shown to act as a protector against various conditions in which free radicals cause molecular and tissue injury. Some of the mechanisms by which melatonin operates as a free radical scavenger and antioxidant have been identified. The importance of endogenous melatonin in cardiovascular health and the benefits of melatonin supplementation in different cardiac pathophysiological disorders have been shown in a variety of model systems. Melatonin continues to attract attention for its potential therapeutic value for cardiovascular toxicity. The therapeutic potential of melatonin in treatment of cardiotoxicities caused by various chemicals along with suggested molecular mechanisms of action for melatonin is reviewed.

Evaluation the Serum Level of Melatonin in Iraqi Patients with Polycystic Ovarian Syndrome

Background: Polycystic Ovarian Syndrome(PCOS) is one of the most frequent gynecological endocrinopathy that occur in premenopausalfemales, with a predominance range from 6%to10% among women of reproductive age.Melatonin (N-acetyl-5-methoxytryptamine), an neurohormone synthesized from the aromatic amino acid tryptophan mainly by the pineal gland of humans.The important of melatonin in human reproduction is still unidentified. A numerous study suggests that melatonin and reproductive hormones are closely related. This concept is based on observation of influence melatonin on sex steroid production at different stages of ovarian follicular maturation as melatonin receptors have been demonstrated at multiple sites in ovary and in intrafollicular fluid. Aim :The study aim to evaluate the role of melatonin in women with polycystic ovarian syndrome. Materials and Methods:A prospective cross-sectional study was designed taking 60 PCOS patients and 30 controls women whose ages were between 15-35 years old, from beginning of January 2019 to ending of April 2019. These patients admitted to obstetrics and gynecology unit at Babylon teaching hospital. And Five ml of blood sample was taken on day 2 of menstrual cycle by vein puncture from each subject enrolled in this study .Blood samples were collected between 07:00am – 08:00 am, and placed into sterile test tubes to serum melatonin estimation.Result: The study showed that there is the significant difference betweenPCOS women and the control group concerning melatonin level,and the highest mean of melatonin was occurred in PCOS women (61.21±13.78vs. 28.61±6.73). And also This study showed that there were the higher means of melatonin in PCOS women with positive family history than PCOS women with negative family history (66.56±11.25vs. 59.26±14.21) with significant relation.Conclusions: Women with PCOS have significant increase of serum melatonin in PCOS women. And also thisstudy could open the way for therapeutic role of melatonin in treatment of PCOS women.

Evaluation of Effect of Topical Melatonin in Treatment of Oral Leukoplakia

Evaluation of Effect of Topical Melatonin in Treatment of Oral Leukoplakia

A Preliminary Phase-2 Study with very High-Dose of Melatonin (1000 mg/day) in Untreatable Advanced Cancer Patients Already Progression on Previous Palliative Therapy with High-Dose Melatonin

It is known since more than 50 years&nbsp;that the pineal gland plays a fundamental role in the natural biological resistance against cancer onset and growth. The anticancer role of the pineal gland is due to the production of several antitumor molecules, the most known of them is the indole hormone melatonin (MLT). Unfortunately, although there are&nbsp;a lot of experimental evidences&nbsp;that&nbsp;MLT&nbsp;is completely non-toxic, no oncologist seem&nbsp;to be interested to the clinical use of MLT in the treatment of human neoplasms, at least from a palliative point of view. However, a&nbsp;few number of clinical studies of MLT in the&nbsp;complementary treatment of cancer has demonstrated that the anticancer activity of MLT is a dose-dependent phenomenon. On this basis,&nbsp;a preliminary study with a very high dose of MLT, consisting of 1000 mg/once day&nbsp;in the evening, was carried out in untreatable cancer patients, who&nbsp;failed to respond to the conventional anticancer therapies, and for whom the only available treatment was the palliative therapy. The treatment was well tolerated, and a disease control was achieved in 54% patients. These preliminary results would justify further clinical studies to generate a new interpretation of&nbsp;cancer control, consisting of&nbsp;the pharmacological reproduction of the same mechanisms responsible for the natural resistance against cancer development.

Myomaker, and Myomixer-Myomerger-Minion modulate the efficiency of skeletal muscle development with melatonin supplementation through Wnt/β-catenin pathway

Melatonin, a pleiotropic hormone secreted from the pineal gland, has been shown to exert beneficial effects in muscle regeneration and repair due to its functional diversity, including anti-inflammation, anti-apoptosis, and anti-oxidative activity. However, little is known about the negative role of melatonin in myogenesis. Here, using skeletal muscle cells, we found that melatonin promoted C2C12 cells proliferation and inhibits differentiation both in C2C12 cells and primary myoblasts in mice. Melatonin administration significantly down-regulated differentiation and fusion related genes and inhibited myotube formation both in C2C12 cells and primary myoblasts in mice. RNA-seq showed that melatonin down-regulated essential fusion pore components Myomaker and Myomixer-Myomerger-Minion. Moreover, melatonin suppressed Wnt/β-catenin signaling. Inhibition of GSK3β by LiCl rescued the influence of melatonin on differentiation efficiency, Myomaker, but not Myomxier in C2C12 cells. In conclusion, melatonin inhibits myogenic differentiation, Myomaker, and Myomixer through reducing Wnt/β-catenin signaling. These data establish a link between melatonin and fusogenic membrane proteins Myomaker and Myomixer, and suggest the new perspective of melatonin in treatment or preventment of muscular diseases.

Role of Melatonin in Treatment of Necrotizing Enterocolitis in Preterm Neonates

AbstractBackground: Necrotizing enterocolitis (NEC) is one of the most dangerous gastrointestinal diseases that affects the neonates especially preterm neonates. It can lead to severe morbidity and even mortality, so early detection of NEC would give us good chance for early prevention and treatment with better prognosis. Free radicals play a significant role in the pathogenesis of neonatal sepsis and NEC. It has been suggested that melatoninas an antioxidant can be used to counteract the toxicity of oxygen radicals that are released during neonatal illness.Aim of Study: Is to Determine the role of melatonin as an adjuvant therapy in treating necrotizing enterocolitis (NEC) in preterm neonates.Patients and Methods: A prospective clinical trial study was conducted on 20 preterm neonates which suffer from NEC diagnosed on the basis of both clinical and laboratory criteria. group (G I) (n=10) received melatonin and antibiotics, while the control group (G II) (n=10) was treated with antibi-otics only. Melatonin was administered as 20 mg for 3 con-secutive days and antibiotics were administered according to a standard protocol protocol and followed-up of symptoms and signs of NEC after 5,10 and 15 days of starting treatment.Results: As regard outcome of NEC, In group I there were 9 (90%) cases improved and 1 (10%) case not improved but In group II there were 5 (50%) cases improved and 5 (50%) cases not improved, so more cases in group I who received melatonin showed improvement of NEC than group II. As regard mortality, one baby (10%) died and 9 (90%) survived in group I compared to 3 babies (30%) died and 7 babies (70%) survived in group II.As regard length of NICU stay the patients who received melatonin (group I) stay for a shorter period in NICU compared to group II who received traditional therapy only.Conclusion: Melatonin administration as an adjuvant therapy in NEC treatment in preterm neonates is associated with improvement of clinical and laboratory outcome.

Doxylamine and melatonin in treatment of sleep disruption in gynecological practice

Symptoms of sleep disruption are widely prevalent in general population, but they are not necessarily form the full clinical presentation of insomnia. Diagnostic process should consider somatic diseases usually accompanied by sleep disruption. This review presents the data on insomnia symptoms in gynecological diseases: menstrual cycle related disorders, endometriosis, peri- and postmenopausal symptoms.

Melatonin in Treatment of Sleep Disorders in Elderly Patients with Chronic Obstructive Pulmonary Disease

Melatonin in Treatment of Sleep Disorders in Elderly Patients with Chronic Obstructive Pulmonary Disease

Melatonin and Respiratory Diseases: A Review.

Melatonin is an indoleamine with potent multifunctional biological and pharmacological effects, both receptor dependent and receptor-independent effects, including antioxidant, anticancer, antitumor, anti-inflammatory, anti-aging, anti-diabetic, antiviral, neuroprotective activities. Melatonin mitigates tissue injury via modification of abnormalities in redox status and other biochemical markers. At the molecular level, the biological and pharmacological activities of melatonin are attributed to the inhibition of nuclear factor-κappa beta (NF-κβ), c-Fos over expression and down-regulation of matrix metalloproteinases-3 (MMP-3), which are regulators of pro-inflammatory and pro-fibrotic cytokines. There are numerous scientific reports on the therapeutic potential of melatonin in treatment of asthma, respiratory diseases for infections, chronic obstructive pulmonary disease, lung cancer, pleural cavity diseases, as well as vascular pulmonary disease. In the present communication, we systematically review the therapeutic potential of melatonin in the treatment of respiratory diseases along with its molecular mechanism of actions.

Combination of Melatonin and Metformin Hydrochloride for Treatment Polycystic Ovarian in Female Rats

Background: Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder, results in menstrual abnormalities, androgynism and infertility. In the case of women or others animals with PCOS wishing to treat infertility with the aim of becoming pregnant, the most commonly used is metformin hydrochloride. Recent studies have analyzed the combination of metformin hydrochloride with melatonin in oncological treatment but not to treatment of polycystic ovary syndrome (PCOS). The aim of the present study was to analyze the effectiveness of the combination of metformin hydrochloride and melatonin in the treatment of PCOS to improve the fertility of rats and your hormonal alterations.Materials, Methods &amp; Results: This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Committee on the Ethics of Animal Experiments of the University of Federal Rural of Pernambuco (Permit Number: 23081.009130/2010). A total of 50 albino Wistar rats were used. The animal laboratory of an academic research environment, were randomly separated into five groups consisting of 10 females each. After inducing PCOS, the rats were treated with metformin hydrochloride, and/or melatonin, and the results compared with standard and ultrasound confirmed. The physiological similarities were confirmed by our academic researchers morphological science, and published to the association results of effects syndrome induction through constant lighting in reputable magazine recently. This article was analyzed histological of the implantation sites and ovaries, and the estradiol and progesterone levels on the seventh day of gestation, and the other rats for monitoring pregnancy and morphological identification of possible fetal abnormalities, weight measurement and quantification of offspring. The rats were anaesthetized with intraperitoneal injections of ketamine hydrochloride (80 mg/kg) and xylazine (6 mg/kg) to allow analysis of the reproductive organs. Main outcome measures: The study included histopathology, histochemical and quantitative (of the implantation sites) tests, ultrasound analysis, weight benchmarking and ovarian histology tests, as well as comparison of serum estradiol and progesterone levels, and the morphological assessment of offspring. Results paper shows pharmacological treatment reduced the time needed for pregnancy, increased the plasma progesterone levels, the number and weight of offspring, and reduced plasma estrogen levels and collagen fiber grade, improving blastocyst-endometrium interaction and fetal development.Discussion: Our team of researchers confirmed in a previous paper; in addition, the main experimental model used in research about PCOS in recent years, and considered appropriate combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the POS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring. The treatment with a combination of metformin hydrochloride and melatonin was more effective against hormonal alterations produced by PCOS, allowing a normalization of biochemical parameters during pregnancy, than monotherapeutic treatment with these drugs. In conclusion, proposed drug combination is a viable option to treatment of polycystic ovary syndrome and improved fetal development. This article allows suggest that further research should be conducted to examine effects associated with these drugs in the treatment of diseases of the female reproductive system experimentally. Only such treatment later in animals and humans suggest.

Therapeutic value of melatonin post-treatment on CCl4-induced fibrotic rat liver.

Melatonin is known for being beneficial in targeting liver diseases. This study aimed to investigate whether melatonin post-treatment is capable of rat carbon tetrachloride (CCl4)-induced liver fibrosis reduction. Thirty-two male Sprague-Dawley rats were divided into 4 groups: normal; fibrosis with CCl4 injection (1 mL/kg) twice weekly for 8 weeks; phosphate-buffered saline (PBS); and melatonin (20 mg/kg) for a further 4 weeks on cessation of CCl4. At the beginning of week 13, liver tissue samples were used for hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), Masson's trichrome (MT), and Oil Red O staining, quantitative real-time PCR (qRT-PCR) analysis of the matrix metalloproteinase-9 (MMP-9), MMP-13, transforming growth factor-β1 (TGF-β1), Bcl-2, and Bax genes as well as immunofluorescence (IF) of the first 3, and sera for measurement of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and hydroxyproline. Chronic administration of CCl4 followed by considerable increase in tissue disruption, macro- and micro-vesicles, collagen, lipid droplets (LDs), AST, ALT, hydroxyproline, TGF-β1, and Bax, and decrease in glycogen depository, albumin, Bcl-2, MMP-9, and MMP-13; however, the pattern was reverse when it comes to melatonin treatment (for all p < 0.05). Our results reveal the beneficial aspects of melatonin in treatment of liver fibrosis probably via inhibition of TGF-β1expression.

Acebutolol and Immediate Release Melatonin in Treatment of Smith-Magenis Syndrome

Acebutolol and Immediate Release Melatonin in Treatment of Smith-Magenis Syndrome

Melatonin in chronic pain syndromes

Melatonin, a neurohormone synthesized by the epiphysis and extrapineal structures, has several functions including chronobiotic, antioxidant, oncostatic, immunomodulating, normothymic and anxiolytic ones. It impacts on the cardiovascular system and the gastrointestinal tract and is involved in reproductive functions, metabolism and body mass regulation. Moreover, recent studies have demonstrated the efficacy of melatonin in pain syndromes. The authors present a literature review on the studies of melatonin in treatment of fibromyalgia, headache, irritated bowel syndrome, chronic back pain and rheumatoid arthritis. Possible mechanisms of analgesic properties of melatonin are discussed. On one hand, there is the improvement of sleep and activation of own adaptive potential of melatonin by normalizing circadian rhythms inevitably disturbed in chronic pain syndromes. On the other hand, there are the data on the analgesic effect of melatonin realized through melatonin receptors and several neurotransmitter systems.

Abstract 4673: A randomized, double-blind, multicenter trial evaluating the chronotherapeutic role of concomitant melatonin in the treatment of stage IIIB and IV non-small cell lung carcinoma.

Abstract Background: A recently published meta-analysis suggests that melatonin administered concurrently with chemotherapy leads to significant improvements in tumor response and survival in solid tumors, however, the role of melatonin in cancer treatment still remains disputable. We investigated the impact of chronotherapeutic administration of melatonin on tumor response and overall survival in stage IIIB and IV non-small cell lung cancer (NSCLC) patients undergoing conventional chemotherapy. Methods: Veteran Affairs Medical Center (VAMC) and Cancer Treatment Centers of America® at Midwestern Regional Medical Center (MRMC), a non-VA site, entered 42 patients each. The patients were randomized to receive placebo 8 am and placebo 8 pm (arm 1; n=29), or melatonin 20 mg 8 am and placebo 8 pm (arm 2; n=27), or placebo 8 am and melatonin 20 mg 8 pm (arm 3; n=28). All study participants received treatment with cisplatin (25 mg/m2/day) followed by etoposide (100 mg/m2/day) chemotherapy. Patient survival was defined as the time between the study start date and date of death from any cause/date of last contact. Kaplan-Meier analysis with log-rank test was used to evaluate the equality of survival distributions across the three treatment arms. Tumor response was evaluated using the RECIST guidelines. Results: 64 patients had stage IV while 20 had stage IIIB disease. 65 patients were males while 19 were females. All patients had expired at the time of this analysis. Mean age at study entry was 61.3 years (57 years for MRMC versus 65.7 for VAMC). There were no significant differences in the three treatment arms with respect to age, gender, tumor stage and performance status. Median survival time in the 3 treatment arms was 10.4 (arm 1), 6.8 (arm 2) and 8.0 (arm 3) months respectively (log rank p=0.81). Similarly, there was no significant difference in the treatment arms with regard to tumor response, such that 48.3%, 37.0% and 32.1% patients had stable disease in arm 1, arm 2 and arm 3 respectively (Chi-square p=0.49). Conclusions: Contrary to the recently reported meta-analysis, we found that neither the addition nor the timing of a high oral dose of melatonin added therapeutically to the combination of cisplatin and etoposide. The melatonin dose used in this study is at least 20x the usual replacement dose and this may have resulted in melatonin being inappropriately present in the circulation during both day and night, an un-physiologic state, which might be responsible for the apparent lack of efficacy of this particular regimen. Citation Format: Robert D. Levin, James F. Grutsch, Christopher G. Lis, Digant Gupta, Patricia A. Wood, William JM Hrushesky. A randomized, double-blind, multicenter trial evaluating the chronotherapeutic role of concomitant melatonin in the treatment of stage IIIB and IV non-small cell lung carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4673. doi:10.1158/1538-7445.AM2013-4673

Melatonin and its correlation with testosterone in polycystic ovarian syndrome

CONTEXT:Polycystic ovarian syndrome (PCOS) is considered to be the most common endocrine disorder affecting women. Melatonin, a small lipophilic indoleamine, and reproductive hormones may be interrelated. Melatonin influences sex steroid production at different stages of ovarian follicular maturation as melatonin receptors have been demonstrated at multiple sites in ovary and in intrafollicular fluid. It plays role as an antioxidant and free radical scavanger which protects follicles from oxidative stress, rescuing them from atresia, leading to complete follicular maturation and ovulation.AIMS:To study the role of melatonin in PCOS and to investigate its correlation with testosterone in patients suffering from PCOS.SETTINGS AND DESIGN:A total of 50 women with PCOS (Rotterdam criteria, 2003) and 50 age and weight matched healthy controls were selected and serum melatonin estimation was done in both the groups and correlated with serum total testosterone levels.MATERIALS AND METHODS:In a case-control study, detailed history, clinical examination and hormonal evaluation [basal levels of leutinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, prolactin, insulin, total testosterone, progesterone and melatonin] were carried out in all the participants including both cases and controls. For melatonin estimation, blood samples were collected between 12:00 am and 04:00 am on day 2nd of menstrual cycle and analyzed by using commercially available enzyme-linked immunosorbent assay kit.STATISTICAL ANALYSIS:Student's t-test was used to compare the significant difference in mean values between cases and control groups. Chi-square test was used to test the significant association between the qualitative variables. Linear correlation coefficient and regression analysis were done to see the amount and direction of relationship between quantitative variables.RESULTS:The mean melatonin level was observed to be significantly increased in patients (63.27 ± 10.97 pg/mL) than in controls (32.51 ± 7.55 pg/mL). Melatonin was found to be raised in all the cases of PCOS (above cut-off value of ≥45 pg/mL, P < 0.001). Total testosterone level was also raised in 72% of patients. Melatonin levels were found to be positively associated with increased testosterone (P < 0.001). In regression analysis using melatonin as dependent variable and testosterone as an independent variable, the value of R2 Χ 100 (percent variation) was found to be 72.1%.CONCLUSIONS:Women with PCOS have significantly raised serum melatonin levels and hyperandrogenemia along with increased number of atretic follicles. Further studies are required to establish a definite role of melatonin in PCOS cases with disturbed hormonal milieu. This could open up the way for therapeutic role of melatonin in treatment of patients suffering from PCOS.

Melatonin in treatment of chronic sleep disorders in adults with autism: a retrospective study.

Melatonin may be used to treat sleep disorders in both children and adults with intellectual disability. The evidence for its efficacy, potential adverse effects and drug interactions are reviewed in the context of prescription of melatonin to patients with autism. This study presents the use of melatonin to treat severe circadian sleep-wake disturbances in 6 adults with autism. Melatonin was initiated at a daily dose of 3 mg at nocturnal bedtime. If this proved ineffective, the melatonin dose was titrated over the following 4 weeks at increments of 3 mg/2 weeks up to a maximum of 9 mg, unless it was tolerated. Assessments included Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I). Melatonin administered in the evening dramatically improved the sleep-wake pattern in all patients. Melatonin appears to be effective in reducing sleep onset latency and is probably effective in improving nocturnal awakenings and total sleep time in adults with autism. Its effectiveness remained stable for the 6-month period of administration. Melatonin was well tolerated in all patients and no side effects were noted during the therapy. Melatonin appears to be promising as an efficient and seemingly safe alternative for treatment of severe circadian sleep disturbances in adults with autism. There may be heterogeneity of response depending on the nature of the sleep problem and cause of the intellectual disability or associated disabilities. Further studies are necessary before firm conclusions can be drawn and guidelines for the use of melatonin in people with autism formulated.

Melatonin in treatment of chronic sleep disorders in adults with autism: a retrospective study.

Melatonin may be used to treat sleep disorders in both children and adults with intellectual disability. The evidence for its efficacy, potential adverse effects and drug interactions are reviewed in the context of prescription of melatonin to patients with autism. This study presents the use of melatonin to treat severe circadian sleep-wake disturbances in 6 adults with autism. Melatonin was initiated at a daily dose of 3 mg at nocturnal bedtime. If this proved ineffective, the melatonin dose was titrated over the following 4 weeks at increments of 3 mg/2 weeks up to a maximum of 9 mg, unless it was tolerated. Assessments included Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I). Melatonin administered in the evening dramatically improved the sleep-wake pattern in all patients. Melatonin appears to be effective in reducing sleep onset latency and is probably effective in improving nocturnal awakenings and total sleep time in adults with autism. Its effectiveness remained stable for the 6-month period of administration. Melatonin was well tolerated in all patients and no side effects were noted during the therapy. Melatonin appears to be promising as an efficient and seemingly safe alternative for treatment of severe circadian sleep disturbances in adults with autism. There may be heterogeneity of response depending on the nature of the sleep problem and cause of the intellectual disability or associated disabilities. Further studies are necessary before firm conclusions can be drawn and guidelines for the use of melatonin in people with autism formulated.

P03-224 Melatonin in treatment of chronic sleep disorders in adults with pervasive development disorders: A retrospective study

Background:Melatonin may be used to treat sleep disorders in both children and adults with intellectual disability. the evidence for its efficacy, potential adverse effects and drug interactions are reviewed in the context of prescribing to people with intellectual disability.Methods:This study presents the use of melatonin to treat severe circadian sleep-wake disturbances in 6 adults with pervasive developmental disorders. Melatonin was initiated at a daily dose of 3 mg at nocturnal bedtime. If this proved ineffective, the melatonin dose was titrated over the following 4 weeks at increments of 3mg/2weeks up to a maximum of 9 mg, unless it was tolerated. Assessments included the Clinical Global Impression-Severity (CGI-S) and CGI-Improvement (CGI-I).Results:Melatonin administered in the evening dramatically improved the sleep-wake pattern in all patients. Melatonin appears to be effective in reducing sleep onset latency and is probably effective in improving nocturnal awakenings and total sleep time in adults with pervasive developmental disorders. Its effectiveness remained stable for the 6-months period of administration. Melatonin was well-tolerated in all patients and no side effects were noted during the therapy.Conclusions:Melatonin appears to be promising as an efficient and seemingly safe alternative for treatment of severe circadian sleep disturbances in adults with intellectual disability. There may be heterogeneity of response depending on the nature of the sleep problem and cause of the intellectual disability or associated disabilities. Further studies are necessary before firm conclusions can be drawn and guidelines for the use of melatonin for people with ID formulated.