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Melatonergic agents influence the sleep-wake and circadian rhythms in healthy and psychiatric participants: a systematic review and meta-analysis of randomized controlled trials. Neuropsychopharmacology 2022; 47:1523-1536. [PMID: 35115662 PMCID: PMC9206011 DOI: 10.1038/s41386-022-01278-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 12/08/2021] [Accepted: 01/12/2022] [Indexed: 11/20/2022]
Abstract
Exogenous melatonergic agents are widely used to treat insomnia and sleep disturbance. Several studies have shown that they might also modulate circadian rhythms. The purpose of this systematic review and meta-analysis was to summarize current knowledge about the effects of melatonin supplements and melatonin agonists on the sleep-wake cycle as well as on the circadian rhythm of melatonin in healthy participants and in patients with psychiatric disorders. The following electronic databases were searched: EMBASE, PubMed, Web of Science, CINAHL, and Cochrane Library. Of the 12,719 articles, we finally selected 30 studies including 1294 healthy participants and 8 studies including 687 patients with psychiatric disorders. Cochrane risk of bias tool was used to assess the risk of bias. Using meta-ANOVA, studies on healthy participants showed advancing effects of melatonergic supplements and agonists on sleep-wake cycle according to dosing time and dosage, despite the fact that the original individual melatonin rhythm was within a normal range (fixed effect model standardized mean difference [95% Confidence Interval] = -0.639[-0.968 to -0.310]). In a limited number of randomized controlled trials with psychiatric patients, the findings seemed similar to those with healthy participants, despite the psychiatric disorders and treatment related factors affecting circadian rhythms. Given the unmet clinical need for evidence-based treatments to correct circadian rhythms in psychiatric disorders, efficacy of melatonergic agents seen in healthy participants, and similarity of findings among psychiatric patients, large scale, well-designed randomized controlled trials are needed to test efficacy on circadian parameters in psychiatric disorders.
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Examining First Night Effect on Sleep Parameters with hd-EEG in Healthy Individuals. Brain Sci 2022; 12:brainsci12020233. [PMID: 35203996 PMCID: PMC8870064 DOI: 10.3390/brainsci12020233] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 02/02/2022] [Accepted: 02/04/2022] [Indexed: 12/04/2022] Open
Abstract
Difficulty sleeping in a novel environment is a common phenomenon that is often described as the first night effect (FNE). Previous works have found FNE on sleep architecture and sleep power spectra parameters, especially during non-rapid eye movement (NREM) sleep. However, the impact of FNE on sleep parameters, including local differences in electroencephalographic (EEG) activity across nights, has not been systematically assessed. Here, we performed high-density EEG sleep recordings on 27 healthy individuals on two nights and examined differences in sleep architecture, NREM (stages 2 and 3) EEG power spectra, and NREM power topography across nights. We found higher wakefulness after sleep onset (WASO), reduced sleep efficiency, and less deep NREM sleep (stage 3), along with increased high-frequency NREM EEG power during the first night of sleep, corresponding to small to medium effect sizes (Cohen’s d ≤ 0.5). Furthermore, study individuals showed significantly lower slow-wave activity in right frontal/prefrontal regions as well as higher sigma and beta activities in medial and left frontal/prefrontal areas, yielding medium to large effect sizes (Cohen’s d ≥ 0.5). Altogether, these findings suggest the FNE is characterized by less efficient, more fragmented, shallower sleep that tends to affect especially certain brain regions. The magnitude and specificity of these effects should be considered when designing sleep studies aiming to compare across night effects.
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3
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Role of Melatonin in the Management of Sleep and Circadian Disorders in the Context of Psychiatric Illness. Curr Psychiatry Rep 2022; 24:623-634. [PMID: 36227449 PMCID: PMC9633504 DOI: 10.1007/s11920-022-01369-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/22/2022] [Indexed: 01/29/2023]
Abstract
PURPOSE OF REVIEW We present a review of research on the role of melatonin in the management of sleep and circadian disorders, stressing current overall view of the knowledge across psychiatric disorders. RECENT FINDINGS Dysregulation of sleep and circadian rhythms has been established in several psychiatric and neurocognitive disorders for long. Recent research confirms this finding consistently across disorders. The secretion of melatonin in schizophrenia and neurocognitive disorders is reduced due to a smaller volume and enlarged calcification of the pineal gland. On the other hand, melatonin dysregulation in bipolar disorder may be more dynamic and caused by light-sensitive melatonin suppression and delayed melatonin secretion. In both cases, exogenous melatonin seems indicated to correct the dysfunction. However, a very limited number of well-designed trials with melatonin to correct sleep and circadian rhythms exist in psychiatric disorders, and the evidence for efficacy is robust only in autism, attention deficit hyperactivity disorder (ADHD), and neurocognitive disorders. This topic has mainly not been of interest for recent work and well-designed trials with objective circadian parameters are few. Overall, recent studies in psychiatric disorders reported that melatonin can be effective in improving sleep parameters such as sleep onset latency, sleep efficiency, and sleep quality. Recent meta-analysis suggests that optimal dosage and dosing time might be important to maximize the efficacy of melatonin. The knowledge base is sufficient to propose well-designed, larger trials with circadian parameters as inclusion and outcome criteria. Based on the partly fragmentary information, we propose testing efficacy in disorders with neurocognitive etiopathology with later and higher dosing, and affective and anxiety disorders with lower and earlier dosing of melatonin. Melatonin is promising for the correction of sleep and circadian abnormalities in psychiatric disorders. However, research results on its effect are still few and need to be accumulated. For effective use of melatonin, it is necessary to consider the appropriate dosage and administration time, depending on the individual abnormality of sleep and circadian rhythms.
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Duan C, Jenkins ZM, Castle D. Therapeutic use of melatonin in schizophrenia: A systematic review. World J Psychiatry 2021; 11:463-476. [PMID: 34513608 PMCID: PMC8394692 DOI: 10.5498/wjp.v11.i8.463] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 07/12/2021] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Sleep dysfunction is a common problem in people with schizophrenia, and side effects of treatment often exacerbate metabolic and cardiovascular risk and may induce extrapyramidal side effects. Melatonin (N-acetyl-5-methoxytryptamine) is an endogenously produced hormone which has demonstrated direct and indirect antioxidant and neuroprotective effects. Previous studies have explored the use of exogenous melatonin in improving sleep outcomes in the general population, yet indications for use in schizophrenia are unclear.
AIM To synthesize the evidence from clinical trials investigating prescribed melatonin as an adjunctive therapy in patients with schizophrenia.
METHODS A systematic literature review of MEDLINE (Ovid), Embase, PsychINFO, and PubMed on the 27/08/20; and CINAHL and Cochrane Library databases, was conducted. Inclusion criteria were: a peer-reviewed clinical trial published in English; included a group of patients with schizophrenia; used melatonin as an adjunctive therapy; and reported any outcome of any duration. Exclusion criteria were: neurodegenerative diseases, primary sleep disorders, co-morbid substance use or animal studies.
RESULTS Fifteen studies were included in the current review with the following primary outcomes: sleep (n = 6), metabolic profile (n = 3), tardive dyskinesia (n = 3), cognitive function (n = 2) and benzodiazepine discontinuation (n = 1).
CONCLUSION Adjunctive melatonin therapy has some positive outcomes for sleep, metabolic profile and tardive dyskinesia in patients with schizophrenia. No beneficial effect of melatonin was observed on outcomes of cognition or benzodiazepine discontinuation. Future studies utilizing larger samples and investigations specifically comparing the effect of melatonin as adjunctive therapy with different antipsychotics in patients with schizophrenia are required.
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Affiliation(s)
- Cathy Duan
- Department of Psychiatry, University of Melbourne, Parkville 3010, VIC, Australia
| | - Zoe M Jenkins
- Department of Psychiatry, University of Melbourne, Parkville 3010, VIC, Australia
- Mental Health Service, St. Vincent's Hospital, Melbourne 3065, VIC, Australia
| | - David Castle
- Department of Psychiatry, University of Melbourne, Parkville 3010, VIC, Australia
- Mental Health Service, St. Vincent's Hospital, Melbourne 3065, VIC, Australia
- Centre for Complex Interventions, Centre for Addictions and Mental Health, Toronto ON M6J 1H4, Canada
- Department of Psychiatry, University of Toronto, Toronto ON M5S, Canada
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5
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Palagini L, Manni R, Aguglia E, Amore M, Brugnoli R, Bioulac S, Bourgin P, Micoulaud Franchi JA, Girardi P, Grassi L, Lopez R, Mencacci C, Plazzi G, Maruani J, Minervino A, Philip P, Royant Parola S, Poirot I, Nobili L, Biggio G, Schroder CM, Geoffroy PA. International Expert Opinions and Recommendations on the Use of Melatonin in the Treatment of Insomnia and Circadian Sleep Disturbances in Adult Neuropsychiatric Disorders. Front Psychiatry 2021; 12:688890. [PMID: 34177671 PMCID: PMC8222620 DOI: 10.3389/fpsyt.2021.688890] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 04/29/2021] [Indexed: 12/14/2022] Open
Abstract
Introduction: Insomnia and circadian rhythm disorders, such as the delayed sleep phase syndrome, are frequent in psychiatric disorders and their evaluation and management in early stages should be a priority. The aim of this paper was to express recommendations on the use of exogenous melatonin, which exhibits both chronobiotic and sleep-promoting actions, for the treatment of these sleep disturbances in psychiatric disorders. Methods: To this aim, we conducted a systematic review according to PRISMA on the use of melatonin for the treatment of insomnia and circadian sleep disorders in neuropsychiatry. We expressed recommendations for the use of melatonin in psychiatric clinical practice for each disorder using the RAND/UCLA appropriateness method. Results: We selected 41 studies, which included mood disorders, schizophrenia, substance use disorders, attention deficit hyperactivity disorders, autism spectrum disorders, neurocognitive disorders, and delirium; no studies were found for both anxiety and eating disorders. Conclusion: The administration of prolonged release melatonin at 2-10 mg, 1-2 h before bedtime, might be used in the treatment of insomnia symptoms or comorbid insomnia in mood disorders, schizophrenia, in adults with autism spectrum disorders, neurocognitive disorders and during sedative-hypnotics discontinuation. Immediate release melatonin at <1 mg might be useful in the treatment of circadian sleep disturbances of neuropsychiatric disorders.
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Affiliation(s)
- Laura Palagini
- Psychiatry Division, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Raffaele Manni
- Unit of Sleep Medicine and Epilepsy, Istituto di Ricovero e Cura a Carattere Scientifico Mondino Foundation, Pavia, Italy
| | - Eugenio Aguglia
- Department of Experimental and Clinical Medicine, Psychiatric Clinic University Hospital “Gaspare Rodolico”, University of Catania, Catania, Italy
| | - Mario Amore
- Section of Psychiatry, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy
- Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico San Martino, Genoa, Italy
| | - Roberto Brugnoli
- Department of Neuroscience, Mental Health, and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sant'Andrea University Hospital, Sapienza University, Rome, Italy
| | - Stéphanie Bioulac
- University Sleep Clinic, Services of Functional Exploration of the Nervous System, University Hospital of Bordeaux, and USR CNRS 3413 SANPSY, University Hospital Pellegrin, University of Bordeaux, Bordeaux, France
| | - Patrice Bourgin
- Institut des Neurosciences Cellulaires et Intégratives, CNRS-UPR 3212, Strasbourg, France
- Centre des troubles du sommeil - CIRCSom, Strasbourg University Hospitals, Strasbourg, France
| | - Jean-Arthur Micoulaud Franchi
- University Sleep Clinic, Services of Functional Exploration of the Nervous System, University Hospital of Bordeaux, and USR CNRS 3413 SANPSY, University Hospital Pellegrin, University of Bordeaux, Bordeaux, France
| | - Paolo Girardi
- Department of Neuroscience, Mental Health, and Sensory Organs (NESMOS), Faculty of Medicine and Psychology, Sant'Andrea University Hospital, Sapienza University, Rome, Italy
| | - Luigi Grassi
- Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, Italy
| | - Régis Lopez
- Service de Neurologie, Centre National de Référence Narcolepsie Hypersomnies, Unité des Troubles du Sommeil, Hôpital Gui-de-Chauliac Montpellier, Montpellier, France
- PSNREC, Univ Montpellier, INSERM, Montpellier, France
| | - Claudio Mencacci
- Department of Neuroscience, Aziende Socio Sanitarie Territoriali Fatebenefratelli Sacco, Milan, Italy
| | - Giuseppe Plazzi
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
- Istituto di Ricovero e Cura a Carattere Scientifico, Institute of Neurological Sciences of Bologna, Bologna, Italy
| | - Julia Maruani
- Département de psychiatrie et d'addictologie, AP-HP, GHU Paris Nord, DMU Neurosciences, Hopital Bichat - Claude Bernard, Paris, France
| | - Antonino Minervino
- Department of Psychiatry, Italian Society of Psychosomatic Medicine (SIMP), Parma, Italy
| | - Pierre Philip
- University Sleep Clinic, Services of Functional Exploration of the Nervous System, University Hospital of Bordeaux, and USR CNRS 3413 SANPSY, University Hospital Pellegrin, University of Bordeaux, Bordeaux, France
| | | | - Isabelle Poirot
- Service de psychiatrie adulte, Hôpital Fontan, CHU de Lille, Lille, France
| | - Lino Nobili
- Department of Neuroscience (DINOGMI), University of Genoa, Genoa, Italy
- Istituto di Ricovero e Cura a Carattere Scientifico, Child Neuropsychiatry Unit, Giannina Gaslini Institute, Genoa, Italy
| | - Giovanni Biggio
- Department of Life and Environmental Sciences, Institute of Neuroscience, CNR, University of Cagliari, Cagliari, Italy
| | - Carmen M. Schroder
- Institut des Neurosciences Cellulaires et Intégratives, CNRS-UPR 3212, Strasbourg, France
- Department of Child and Adolescent Psychiatry, Strasbourg University Hospitals, Strasbourg, France
| | - Pierre A. Geoffroy
- Département de psychiatrie et d'addictologie, AP-HP, GHU Paris Nord, DMU Neurosciences, Hopital Bichat - Claude Bernard, Paris, France
- GHU Paris - Psychiatry & Neurosciences, Paris, France
- CNRS UPR 3212, Institute for Cellular and Integrative Neurosciences, Strasbourg, France
- Université de Paris, NeuroDiderot, Inserm, Paris, France
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Gao W, Li G, Han X, Song Z, Zhao S, Sun F, Ma H, Cui A, Wang Y, Liu X, Chen Y, Zhang L, Ma G, Tang X. Regional brain network and behavioral alterations in EGR3 gene transfected rat model of schizophrenia. Brain Imaging Behav 2021; 15:2606-2615. [PMID: 33723811 DOI: 10.1007/s11682-021-00462-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 05/31/2020] [Accepted: 06/10/2020] [Indexed: 12/25/2022]
Abstract
Schizophrenia is a severe psychiatric disease while its etiology and effective treatment are not completely clear. A rat model of schizophrenia was previously established by transfecting EGR3 gene into the hippocampus of rats. This study aimed to investigate the behavioral and cerebral alterations of the schizophrenic model rats and the risperidone effects. Twenty-six rats were divided into 3 groups: schizophrenia model group (E group), risperidone treatment group (T group), and healthy control group (H group). Morris water maze and open field test were used as behavioral tests, resting-state functional magnetic resonance imaging (fMRI) was performed after EGR3 gene transfection and risperidone therapy. Graph analyses were used for examining cerebral alterations of the rats. Behavioral tests demonstrated reduced spatial working memory and exploring unfamiliar space ability in schizophrenic model rats. Graph analyses revealed reduced regional architectures in the olfactory bulb, nucleus accumbens, and pineal gland in group E compared to group H (p < 0.05), while group T showed increased regional architecture in pineal gland compared to group E (p < 0.05). Besides, the regional architectures in the olfactory bulb, nucleus accumbens were lower in group T than group H, while the hippocampus showed increased regional architecture in group T compared to group H (p < 0.05). Schizophrenia induced several regional alterations in the cerebrum while risperidone can reverse part of these alterations. This study lends support for future research on the pathology of schizophrenia and provides new insights on the role of risperidone in schizophrenia.
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Affiliation(s)
- Wenwen Gao
- Department of Radiology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Chaoyang District, Beijing, 100029, China
| | - Guangfei Li
- School of Life Science, Beijing Institute of Technology, No.5 Zhongguancun South Street, Haidian District, Beijing, 100081, China
| | - Xiaowei Han
- Department of Radiology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Chaoyang District, Beijing, 100029, China.,Graduate School of Peking Union Medical College, Beijing, 100006, China
| | - Zeyu Song
- School of Life Science, Beijing Institute of Technology, No.5 Zhongguancun South Street, Haidian District, Beijing, 100081, China
| | - Shuai Zhao
- Changzhi Medical College, Shanxi, 046000, China
| | - Feiyi Sun
- School of Life Science, Beijing Institute of Technology, No.5 Zhongguancun South Street, Haidian District, Beijing, 100081, China
| | - Hong Ma
- School of Life Science, Beijing Institute of Technology, No.5 Zhongguancun South Street, Haidian District, Beijing, 100081, China
| | - Ailing Cui
- Anatomy Department of Changzhi Medical College, Shanxi, 046000, China
| | - Yige Wang
- Department of Radiology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Chaoyang District, Beijing, 100029, China
| | - Xiuxiu Liu
- Department of Radiology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Chaoyang District, Beijing, 100029, China
| | - Yue Chen
- Department of Radiology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Chaoyang District, Beijing, 100029, China
| | - Lu Zhang
- Department of Science and Education, Shangluo Central Hospital, Shangluo, 726000, China
| | - Guolin Ma
- Department of Radiology, China-Japan Friendship Hospital, No.2 Yinghuayuan East Street, Chaoyang District, Beijing, 100029, China.
| | - Xiaoying Tang
- School of Life Science, Beijing Institute of Technology, No.5 Zhongguancun South Street, Haidian District, Beijing, 100081, China.
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7
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Geoffroy PA, Micoulaud Franchi JA, Lopez R, Schroder CM. The use of melatonin in adult psychiatric disorders: Expert recommendations by the French institute of medical research on sleep (SFRMS). L'ENCEPHALE 2019; 45:413-423. [PMID: 31248601 DOI: 10.1016/j.encep.2019.04.068] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 04/08/2019] [Indexed: 12/11/2022]
Abstract
Melatonin is a hormone secreted by the pineal gland at night. This hormone has many physiological functions, the main one being to synchronise individuals' biological rhythms. Exogenous melatonin has the same chronobiotic action, even at small doses (0.125mg). In addition, a sleep-inducing (soporific) action appears to occur in a dose-effect relationship, i.e. as the dose increases. In psychiatric disorders, these two effects could have interesting applications in clinical practice. The French institute of medical research on sleep (SFRMS) appointed a group of experts to conduct a consensus conference to study the indications of melatonin and the conditions of its prescription. An account of the conclusions on adult psychiatric disorders (presented orally at the Congress on Sleep in Marseille, 23 November 2017) is given here. Exogenous melatonin proves to be useful among patients with a stabilized psychiatric disorder or in remission, to prevent relapse in case of associated complaints of insomnia, poor quality sleep or delayed sleep phase syndrome. During acute phases, melatonin could be used as an adjuvant treatment when there are insomnia symptoms, in mood disorders (bipolar disorder, major depressive disorder, seasonal affective disorder), in attention deficit hyperactivity disorder (ADHD), in peri-surgical anxiety and in schizophrenia. In somatoform disorders, melatonin is a possible treatment for painful symptoms in fibromyalgia, irritable bowel syndrome, functional dyspeptic syndrome and temporomandibular joint dysfunction.
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Affiliation(s)
- P A Geoffroy
- Sleep Disorders Center & CIRCSom (International Research Center for ChronoSomnology), University Hospital, 1, place de l'hôpital, 67000 Strasbourg, France; CNRS UPR 3212, Institute for Cellular and Integrative Neurosciences, 5, rue Blaise-Pascal, 67000 Strasbourg, France; Paris Diderot University - Paris VII, 5, rue Thomas-Mann, 75013 Paris, France.
| | - J-A Micoulaud Franchi
- Services d'explorations fonctionnelles du système nerveux, clinique du sommeil, CHU de Bordeaux, 33076 Bordeaux, France; USR CNRS 3413 SANPSY, université de Bordeaux, CHU de Pellegrin, 33076 Bordeaux, France
| | - R Lopez
- Unité des troubles du sommeil, département de neurologie, centre national de référence narcolepsie, hypersomnies rares, hôpital Gui de Chauliac, 34000 Montpellier, France; Inserm U1061, 34000 Montpellier, France
| | - C M Schroder
- Sleep Disorders Center & CIRCSom (International Research Center for ChronoSomnology), University Hospital, 1, place de l'hôpital, 67000 Strasbourg, France; CNRS UPR 3212, Institute for Cellular and Integrative Neurosciences, 5, rue Blaise-Pascal, 67000 Strasbourg, France; Department of Child and Adolescent Psychiatry, Strasbourg University Hospital, 1, place de l'hôpital, 67091 Strasbourg cedex, France
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8
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Bastos MAV, Oliveira Bastos PRHD, Portella RB, Soares LFG, Conde RB, Rodrigues PMF, Lucchetti G. Pineal gland and schizophrenia: A systematic review and meta-analysis. Psychoneuroendocrinology 2019; 104:100-114. [PMID: 30831343 DOI: 10.1016/j.psyneuen.2019.02.024] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 01/17/2019] [Accepted: 02/24/2019] [Indexed: 12/29/2022]
Abstract
Melatonin (MLT), the main hormone of the pineal gland (PG), is assumed to support initiation and maintenance of sleep, and a stable sleep-wake cycle, exerting antioxidative and neuroprotective actions. Evidence demonstrates that sleep and circadian rhythm abnormalities are very common in schizophrenia patients. Some imaging studies suggest structural abnormalities of the PG in these patients as well. We aimed to critically appraise the literature on PG imaging and melatonin secretion in schizophrenia patients, in comparison to matched healthy controls, and to review placebo-controlled trials of add-on exogenous MLT treatment in schizophrenia patients. In this systematic review, twenty-nine studies were included. Meta-analytical evaluation of data was possible only for MLT secretion finding that midnight plasma levels were significantly reduced in individuals with schizophrenia as compared to healthy controls (Hedge`s g = 1.32, p < 0.01). Imaging studies demonstrated greater prevalence of enlarged calcifications (>1 cm) of the PG (2 out of 2 computed tomography studies) and smaller PG volume (2 out of 3 magnetic resonance studies) compared with healthy controls. Anatomic and functional abnormalities of the PG were not associated with duration of illness or with treatment factors, maybe suggesting them to be primary characteristics of the disease and genetically based. Add-on MLT treatment leads to a modest improvement of objective and subjective sleep quality, of metabolic adverse effects of antipsychotics, and of tardive dyskinesia symptoms in schizophrenia patients. It remains to be established whether MLT treatment in prodromal phases of the disease could prevent neurostructural abnormalities.
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Affiliation(s)
- Marco Aurélio Vinhosa Bastos
- Federal University of Mato Grosso do Sul, Postgraduate Program in Health and Development, Av. Senador Filinto Muller, s/n - Cidade Universitária, Campo Grande, MS, 79070-900, Brazil.
| | - Paulo Roberto Haidamus de Oliveira Bastos
- Federal University of Mato Grosso do Sul, Postgraduate Program in Health and Development, Av. Senador Filinto Muller, s/n - Cidade Universitária, Campo Grande, MS, 79070-900, Brazil
| | - Renata Boschi Portella
- Federal University of Mato Grosso do Sul, Faculty of Medicine, Av. Senador Filinto Muller, s/n - Cidade Universitária, Campo Grande, MS, 79070-900, Brazil
| | - Leonardo Fabrício Gomes Soares
- Federal University of Mato Grosso do Sul, Postgraduate Program in Health and Development, Av. Senador Filinto Muller, s/n - Cidade Universitária, Campo Grande, MS, 79070-900, Brazil
| | - Ricardo Brilhante Conde
- Proexames Imaging Clinic, Av. Mato Grosso, 1772 - Centro, Campo Grande, MS, 79020-201, Brazil
| | | | - Giancarlo Lucchetti
- Federal University of Juiz de Fora, School of Medicine, Av. Eugênio do Nascimento, s/n - Dom Bosco, Juiz de Fora, MG, 36036-330, Brazil
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Abstract
Schizophrenia is a major psychiatric disorder that has a massive, long-lasting negative impact on the patients as well as society. While positive symptoms (i.e., delusions and hallucinations), negative symptoms (i.e., anhedonia, social withdrawal), and cognitive impairments are traditionally considered the most prominent features of this disorder, the role of sleep and sleep disturbances has gained increasing prominence in clinical practice. Indeed, the vast majority of patients with schizophrenia report sleep abnormalities, which tend to precede illness onset and can predict an acute exacerbation of psychotic symptoms. Furthermore, schizophrenia patients often have a comorbid sleep disorder, including insomnia, obstructive sleep apnea, restless leg syndrome, or periodic limb movement disorder. Despite accumulating data, the links between sleep disorders and schizophrenia have not been thoroughly examined, in part because they are difficult to disentangle, as numerous factors contribute to their comorbidity, including medication status. Additionally, sleep disorders are often not the primary focus of clinicians treating this population, despite studies suggesting that comorbid sleep disorders carry their own unique risks, including worsening of psychotic symptoms and poorer quality of life. There is also limited information about effective management strategies for schizophrenia patients affected by significant sleep disturbances and/or sleep disorders. To begin addressing these issues, the present review will systematically examine the literature on sleep disorders and schizophrenia, focusing on studies related to 1) links between distinct sleep disorders and schizophrenia; 2) risks unique to patients with a comorbid sleep disorder; and 3) and management challenges and strategies.
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Affiliation(s)
- Rachel E Kaskie
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
| | - Bianca Graziano
- Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Fabio Ferrarelli
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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10
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Abstract
Sleep disturbances are prevalent in patients with schizophrenia and play a critical role in the morbidity and mortality associated with the illness. Subjective and objective assessments of sleep in patients with schizophrenia have identified certain consistent findings. Findings related to the sleep structure abnormalities have shown correlations with important clinical aspects of the illness. Disruption of specific neurotransmitter systems and dysregulation of clock genes may play a role in the pathophysiology of schizophrenia-related sleep disturbances. Antipsychotic medications play an important role in the treatment of sleep disturbances in these patients and have an impact on their sleep structure.
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Affiliation(s)
- Jayesh Kamath
- Department of Psychiatry, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-6415, USA.
| | - Sundeep Virdi
- Department of Psychiatry, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-6415, USA
| | - Andrew Winokur
- Department of Psychiatry, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-6415, USA
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11
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Baandrup L, Jennum PJ. A validation of wrist actigraphy against polysomnography in patients with schizophrenia or bipolar disorder. Neuropsychiatr Dis Treat 2015; 11:2271-7. [PMID: 26357475 PMCID: PMC4559245 DOI: 10.2147/ndt.s88236] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Sleep disturbances are frequent in patients with schizophrenia or bipolar disorder. Actigraphy has been established as a generally reliable method to examine these disturbances across varying time spans, but the validity against polysomnography (PSG) is not well investigated for this population. We validated wrist-worn actigraphy against PSG in a population of chronic, medicated patients with schizophrenia or bipolar disorder. PATIENTS AND METHODS From a clinical trial, we derived data from 37 patients with schizophrenia and five patients with bipolar disorder who were examined with one-night PSG and concomitant actigraphy. The following sleep variables were compared between the two methods: total sleep time, sleep efficiency, sleep latency, number of awakenings, and time awake after sleep onset. The degree of consistency between the two methods was evaluated using the intra-class correlation coefficient and Bland-Altman plots. Subgroup analyses included splitting the analyses according to sex, diagnosis, and duration of wakefulness after sleep onset. PSG was considered the gold standard. RESULTS The intraclass correlation coefficient was high for total sleep time, moderate for the number of awakenings, and low or zero for the other examined sleep variables. These findings were reproduced in the subgroup analyses that compared men and women, as well as patients with bipolar versus schizophrenia spectrum disorders. When excluding patients with extensive periods of wakefulness after the initial sleep period (wake after sleep onset > 100 minutes), the reliability of the actigraphy-derived sleep variables markedly improved. CONCLUSION Actigraphy reliably measures the total sleep time in this specific patient population. For patients without extensive periods of wakefulness after sleep onset, actigraphy might provide a useful measure of sleep efficiency, sleep latency, and number of awakenings.
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Affiliation(s)
- Lone Baandrup
- Center for Neuropsychiatric Schizophrenia Research (CNSR), Copenhagen University Hospital, Mental Health Center Glostrup, Mental Health Services - Capital Region of Denmark, Glostrup, Denmark ; Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Copenhagen University Hospital, Mental Health Center Glostrup, Mental Health Services - Capital Region of Denmark, Glostrup, Denmark
| | - Poul Jørgen Jennum
- Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, Center for Healthy Ageing, Faculty of Health Sciences, University of Copenhagen, Rigshospitalet, Glostrup, Denmark
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Monti JM, BaHammam AS, Pandi-Perumal SR, Bromundt V, Spence DW, Cardinali DP, Brown GM. Sleep and circadian rhythm dysregulation in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2013; 43:209-16. [PMID: 23318689 DOI: 10.1016/j.pnpbp.2012.12.021] [Citation(s) in RCA: 107] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2012] [Revised: 12/04/2012] [Accepted: 12/27/2012] [Indexed: 12/18/2022]
Abstract
Sleep-onset and maintenance insomnia is a common symptom in schizophrenic patients regardless of either their medication status (drug-naive or previously treated) or the phase of the clinical course (acute or chronic). Regarding sleep architecture, the majority of studies indicate that non-rapid eye movement (NREM), N3 sleep and REM sleep onset latency are reduced in schizophrenia, whereas REM sleep duration tends to remain unchanged. Many of these sleep disturbances in schizophrenia appear to be caused by abnormalities of the circadian system as indicated by misalignments of the endogenous circadian cycle and the sleep-wake cycle. Circadian disruption, sleep onset insomnia and difficulties in maintaining sleep in schizophrenic patients could be partly related to a presumed hyperactivity of the dopaminergic system and dysfunction of the GABAergic system, both associated with core features of schizophrenia and with signaling in sleep and wake promoting brain regions. Since multiple neurotransmitter systems within the CNS can be implicated in sleep disturbances in schizophrenia, the characterization of the neurotransmitter systems involved remains a challenging dilemma.
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Affiliation(s)
- Jaime M Monti
- Department of Pharmacology and Therapeutics, Clinics Hospital, Montevideo, 11600, Uruguay
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13
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Role of melatonin in schizophrenia. Int J Mol Sci 2013; 14:9037-50. [PMID: 23698762 PMCID: PMC3676771 DOI: 10.3390/ijms14059037] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Revised: 04/09/2013] [Accepted: 04/10/2013] [Indexed: 02/07/2023] Open
Abstract
Schizophrenia is a chronic mental disease that disturbs several cognitive functions, such as memory, thought, perception and volition. Schizophrenia’s biological etiology is multifactorial and is still under investigation. Melatonin has been involved in schizophrenia since the first decades of the twentieth century. Research into melatonin regarding schizophrenia has followed two different approaches. The first approach is related to the use of melatonin as a biological marker. The second approach deals with the clinical applications of melatonin as a drug treatment. In this paper, both aspects of melatonin application are reviewed. Its clinical use in schizophrenia is emphasized.
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14
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Abstract
The sleep/wake cycle is arguably the most familiar output of the circadian system, however, sleep is a complex biological process that arises from multiple brain regions and neurotransmitters, which is regulated by numerous physiological and environmental factors. These include a circadian drive for wakefulness as well as an increase in the requirement for sleep with prolonged waking (the sleep homeostat). In this chapter, we describe the regulation of sleep, with a particular emphasis on the contribution of the circadian system. Since their identification, the role of clock genes in the regulation of sleep has attracted considerable interest, and here, we provide an overview of the interplay between specific elements of the molecular clock with the sleep regulatory system. Finally, we summarise the role of the light environment, melatonin and social cues in the modulation of sleep, with a focus on the role of melanopsin ganglion cells.
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Affiliation(s)
- Simon P Fisher
- Biosciences Division, SRI International, Centre for Neuroscience, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA
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15
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Baandrup L, Jennum P, Lublin H, Glenthoj B. Treatment options for residual insomnia in schizophrenia. Acta Psychiatr Scand 2013; 127:81-2. [PMID: 23106614 DOI: 10.1111/acps.12016] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Lone Baandrup
- Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, Copenhagen University Hospital, Glostrup, Denmark.
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16
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Bellapart J, Boots R. Potential use of melatonin in sleep and delirium in the critically ill. Br J Anaesth 2012; 108:572-80. [DOI: 10.1093/bja/aes035] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
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Borba CP, Fan X, Copeland PM, Paiva A, Freudenreich O, Henderson DC. Placebo-controlled pilot study of ramelteon for adiposity and lipids in patients with schizophrenia. J Clin Psychopharmacol 2011; 31:653-8. [PMID: 21869685 PMCID: PMC3725551 DOI: 10.1097/jcp.0b013e31822bb573] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Few interventions have been successful to prevent or reverse the medical complications associated with antipsychotic agents in the schizophrenia population. In particular, no single agent can correct multiple metabolic abnormalities such as insulin resistance, hyperlipidemia, inflammation, obesity, and fat distribution. We now report a randomized placebo-controlled pilot study to examine the effects of ramelteon on obesity and metabolic disturbances among subjects with schizophrenia. METHODS A double-blind, placebo-controlled, 8-week pilot trial was conducted, adding ramelteon 8 mg/d to stable outpatients with schizophrenia. Vital signs and anthropometric measurements, including height, weight, waist circumference, and body fat were assessed, and laboratory assays were tracked to monitor changes in metabolic markers. RESULTS Twenty-five subjects were randomly assigned to treatment with study drug or placebo, and 20 subjects were included in the final analysis. Ramelteon did not improve anthropometric measurements, glucose metabolism, and inflammatory markers. There was, however, a significant decrease in total cholesterol and ratio of cholesterol to high-density lipoprotein in the ramelteon group. Although the standard anthropometric measures did not show significant change, the dual-energy x-ray absorptiometry scan showed a trend toward reduction in fat in the abdominal and trunk areas with a moderate effect size. CONCLUSIONS Although ramelteon decreased cholesterol, treatment may have to be longer than 8 weeks and with a higher dose for maximal effect of ramelteon for body fat and lipid changes. Future studies are needed for patients with schizophrenia with a larger sample size to fully understand ramelteon's effects on abdominal adiposity and lipids.
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Affiliation(s)
- Christina P.C. Borba
- Schizophrenia Program, Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA
| | - Xiaoduo Fan
- Schizophrenia Program, Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA
| | - Paul M. Copeland
- Harvard Medical School, Boston, MA,Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Alexander Paiva
- Schizophrenia Program, Massachusetts General Hospital, Boston, MA
| | - Oliver Freudenreich
- Schizophrenia Program, Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA
| | - David C. Henderson
- Schizophrenia Program, Massachusetts General Hospital, Boston, MA,Harvard Medical School, Boston, MA
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Sarkar S, Katshu MZUH, Nizamie SH, Praharaj SK. Slow wave sleep deficits as a trait marker in patients with schizophrenia. Schizophr Res 2010; 124:127-33. [PMID: 20826077 DOI: 10.1016/j.schres.2010.08.013] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2010] [Revised: 07/24/2010] [Accepted: 08/09/2010] [Indexed: 10/19/2022]
Abstract
BACKGROUND Among the sleep abnormalities found in schizophrenia, slow wave sleep deficits have been found to persist even after the resolution of active psychotic symptoms. Further, such abnormalities are observed in young healthy individuals at high risk of schizophrenia, which suggest that slow wave sleep deficits might be trait marker in schizophrenia. METHODS Sleep EEG was recorded in 20 right handed patients aged 18-45 years with ICD-10 DCR diagnosis of schizophrenia, 14 first degree relatives and 20 age and sex matched controls. Patients were rated on Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) for assessment of psychopathology. RESULTS There was significant difference between the three groups in total sleep period (p<.01), total sleep time (p<.01), stage shifts (p<.05), stage 1 percentage of total sleep time (p<.05), stage 2 duration (p<.05), stage 3 latency (p<.05), stage 4 duration (p<.01) and stage 4 percentage of total sleep time (p<.01). There was significant positive correlation of REM percentage of total sleep time with BPRS total score (r(s) = .488, p = .029) and PANSS positive score (r(s) = .583, p = .007), whereas significant negative correlation of REM latency was found with BPRS total score (r(s) = -.640, p = .002) and PANSS positive score (r(s) = -.657, p = .002) in the patients. CONCLUSIONS Slow wave sleep deficits are a possible trait marker in patients with schizophrenia, which needs replication in further studies.
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Affiliation(s)
- Sukanto Sarkar
- Central Institute of Psychiatry, Kanke, Ranchi, Jharkhand, India.
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Maldonado MD, Reiter RJ, Pérez-San-Gregorio MA. Melatonin as a potential therapeutic agent in psychiatric illness. Hum Psychopharmacol 2009; 24:391-400. [PMID: 19551767 DOI: 10.1002/hup.1032] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The aim of this review was to summarize the potential use of melatonin in the treatment of mental disorders, specifically bipolar disorders, depression, and schizophrenia. To date, melatonin has been most commonly used in psychiatry because of its hypnotic, rhythm resynchronizing, and antioxidant actions. Here, we examine other properties of the melatonin including its anti-inflammatory, antinociceptive, anxiolytic, and drug detoxification actions as well as its protective effects against neural loss. The brain is an intricate sensory and motor organ which receives information from both the external and internal environments. It transduces information into complex chemical and electrical signals which are transmitted throughout the central nervous system (CNS) and the organism. The pathogenesis of mental disorders remains ambiguous and neuroinflammation has been proposed as a causative agent. We consider the potential contributions of melatonin as therapeutic agent in CNS and during neuroinflammation in mental disorders.
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Affiliation(s)
- Maria D Maldonado
- Department of Medical Biochemistry and Molecular Biology, University of Seville Medical School, Seville, Spain.
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Hardeland R. New approaches in the management of insomnia: weighing the advantages of prolonged-release melatonin and synthetic melatoninergic agonists. Neuropsychiatr Dis Treat 2009; 5:341-54. [PMID: 19557144 PMCID: PMC2699659 DOI: 10.2147/ndt.s4234] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2009] [Indexed: 12/12/2022] Open
Abstract
Hypnotic effects of melatonin and melatoninergic drugs are mediated via MT(1) and MT(2) receptors, especially those in the circadian pacemaker, the suprachiasmatic nucleus, which acts on the hypothalamic sleep switch. Therefore, they differ fundamentally from GABAergic hypnotics. Melatoninergic agonists primarily favor sleep initiation and reset the circadian clock to phases allowing persistent sleep, as required in circadian rhythm sleep disorders. A major obstacle for the use of melatonin to support sleep maintenance in primary insomnia results from its short half-life in the circulation. Solutions to this problem have been sought by developing prolonged-release formulations of the natural hormone, or melatoninergic drugs of longer half-life, such as ramelteon, tasimelteon and agomelatine. With all these drugs, improvements of sleep are statistically demonstrable, but remain limited, especially in primary chronic insomnia, so that GABAergic drugs may be indicated. Melatoninergic agonists do not cause next-day hangover and withdrawal effects, or dependence. They do not induce behavioral changes, as sometimes observed with z-drugs. Despite otherwise good tolerability, the use of melatoninergic drugs in children, adolescents, and during pregnancy has been a matter of concern, and should be avoided in autoimmune diseases and Parkinsonism. Problems and limits of melatoninergic hypnotics are compared.
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Affiliation(s)
- Rüdiger Hardeland
- Johann Friedrich Blumenbach Institute of Zoology and Anthropology, University of Göttingen, Germany.
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Pandi-Perumal SR, Srinivasan V, Spence DW, Cardinali DP. Role of the melatonin system in the control of sleep: therapeutic implications. CNS Drugs 2008; 21:995-1018. [PMID: 18020480 DOI: 10.2165/00023210-200721120-00004] [Citation(s) in RCA: 102] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The circadian rhythm of pineal melatonin secretion, which is controlled by the suprachiasmatic nucleus (SCN), is reflective of mechanisms that are involved in the control of the sleep/wake cycle. Melatonin can influence sleep-promoting and sleep/wake rhythm-regulating actions through the specific activation of MT(1) (melatonin 1a) and MT(2) (melatonin 1b) receptors, the two major melatonin receptor subtypes found in mammals. Both receptors are highly concentrated in the SCN. In diurnal animals, exogenous melatonin induces sleep over a wide range of doses. In healthy humans, melatonin also induces sleep, although its maximum hypnotic effectiveness, as shown by studies of the timing of dose administration, is influenced by the circadian phase. In both young and elderly individuals with primary insomnia, nocturnal plasma melatonin levels tend to be lower than those in healthy controls. There are data indicating that, in affected individuals, melatonin therapy may be beneficial for ameliorating insomnia symptoms. Melatonin has been successfully used to treat insomnia in children with attention-deficit hyperactivity disorder or autism, as well as in other neurodevelopmental disorders in which sleep disturbance is commonly reported. In circadian rhythm sleep disorders, such as delayed sleep-phase syndrome, melatonin can significantly advance the phase of the sleep/wake rhythm. Similarly, among shift workers or individuals experiencing jet lag, melatonin is beneficial for promoting adjustment to work schedules and improving sleep quality. The hypnotic and rhythm-regulating properties of melatonin and its agonists (ramelteon, agomelatine) make them an important addition to the armamentarium of drugs for treating primary and secondary insomnia and circadian rhythm sleep disorders.
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Affiliation(s)
- Seithikurippu R Pandi-Perumal
- Comprehensive Center for Sleep Medicine, Department of Pulmonary, Critical Care, and Sleep Medicine, Mt Sinai School of Medicine, New York, New York 10029, USA.
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Verhulst SL, Schrauwen N, De Backer WA, Desager KN. First night effect for polysomnographic data in children and adolescents with suspected sleep disordered breathing. Arch Dis Child 2006; 91:233-7. [PMID: 16352624 PMCID: PMC2065916 DOI: 10.1136/adc.2005.085365] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/28/2005] [Indexed: 11/04/2022]
Abstract
AIMS To assess the presence of a first night effect (FNE) in children and adolescents and to examine if a single night polysomnography (PSG) is sufficient for diagnosing obstructive sleep apnoea syndrome (OSAS). METHODS Prospective case study of 70 patients (group 1: 2-6 years, n = 22; group 2: 7-12 years, n = 32; group 3: 13-17 years, n = 16) referred for OSAS. Diagnostic criteria for OSAS: one or more of the following: (1) obstructive apnoea index (OAI) > or =1; (2) obstructive apnoea hypopnoea index (oAHI) > or =2; (3) SaO2 < or =89% in association with obstruction. RESULTS In all age groups, but mainly in the oldest children, REMS increased during the second night, mainly at the expense of stage 2 sleep. The first night PSG correctly identified OSAS in 86%, 91%, and 100% of the children for groups 1, 2, and 3 respectively. This represents 9% false negatives for OSAS when only the first night PSG was used. All cases missed had mild OSAS, except for one with oAHI >5 on night 2. There were also seven patients with OSAS on night 1 but with a normal PSG on night 2: all had oAHI <5. CONCLUSION There is a FNE in children and adolescents. A single night PSG is sufficient for diagnosing OSAS, but in cases with a suggestive history and examination and with a negative first night, a second night study might be advisable.
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Affiliation(s)
- S L Verhulst
- Department of Pediatrics, University Hospital of Antwerp, Belgium.
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Buscemi N, Vandermeer B, Hooton N, Pandya R, Tjosvold L, Hartling L, Vohra S, Klassen TP, Baker G. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ 2006; 332:385-93. [PMID: 16473858 PMCID: PMC1370968 DOI: 10.1136/bmj.38731.532766.f6] [Citation(s) in RCA: 279] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/18/2005] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To conduct a systematic review of the efficacy and safety of exogenous melatonin in managing secondary sleep disorders and sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder. DATA SOURCES 13 electronic databases and reference lists of relevant reviews and included studies; Associated Professional Sleep Society abstracts (1999 to 2003). STUDY SELECTION The efficacy review included randomised controlled trials; the safety review included randomised and non-randomised controlled trials. QUALITY ASSESSMENT Randomised controlled trials were assessed by using the Jadad Scale and criteria by Schulz et al, and non-randomised controlled trials by the Downs and Black checklist. DATA EXTRACTION AND SYNTHESIS One reviewer extracted data and another reviewer verified the data extracted. The inverse variance method was used to weight studies and the random effects model was used to analyse data. MAIN RESULTS Six randomised controlled trials with 97 participants showed no evidence that melatonin had an effect on sleep onset latency in people with secondary sleep disorders (weighted mean difference -13.2 (95% confidence interval -27.3 to 0.9) min). Nine randomised controlled trials with 427 participants showed no evidence that melatonin had an effect on sleep onset latency in people who had sleep disorders accompanying sleep restriction (-1.0 (-2.3 to 0.3) min). 17 randomised controlled trials with 651 participants showed no evidence of adverse effects of melatonin with short term use (three months or less). CONCLUSIONS There is no evidence that melatonin is effective in treating secondary sleep disorders or sleep disorders accompanying sleep restriction, such as jet lag and shiftwork disorder. There is evidence that melatonin is safe with short term use.
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Affiliation(s)
- Nina Buscemi
- University of Alberta/Capital Health Evidence-based Practice Centre, Department of Pediatrics, University of Alberta, Edmonton, AB, Canada T6G 2J3.
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Zisapel N, Tarrasch R, Laudon M. The relationship between melatonin and cortisol rhythms: clinical implications of melatonin therapy. Drug Dev Res 2005. [DOI: 10.1002/ddr.20014] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Abstract
The synchrony between the individual brain and its environment is maintained by a system of internal clocks that together reflect the temporal organization of the organism. Extending the theoretical work of Edelman and others, the temporal organization of the brain is posited as functioning through "re-entry" and "temporal tagging" and binds the wide range of possible times to a unified cognitive experience which is held in unison with the outside world. Dysfunction in this system is reflected in the temporal discord seen in cases of aging, sleep disorder, jet-lag, and shift-work, as well as in mental disorders and drug-induced changes in consciousness. The extent to which neuroendocrine structures contribute to the neurocognitive mechanisms which underlie consciousness has so far not been explored. Therefore, neuroendocrine mechanisms contributing to the temporal organization of the brain are reviewed. It is concluded that time-and its neuroendocrine correlate melatonin-is a binding principle for organizing conscious experience.
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