Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendationResearch in context
Summary: Background: Melatonin prescriptions for children and adolescents have increased substantially during the last decade. Existing clinical recommendations focus on melatonin as a treatment for insomnia related to neurodevelopmental disorders. To help guide clinical decision-making, we aimed t...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-07-01
|
| Series: | EClinicalMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589537023002250 |
| _version_ | 1827905876370915328 |
|---|---|
| author | Henriette Edemann-Callesen Henning Keinke Andersen Anja Ussing Anne Virring Poul Jennum Nanette Mol Debes Torben Laursen Lone Baandrup Christina Gade Jette Dettmann Jonas Holm Camilla Krogh Kirsten Birkefoss Simon Tarp Mina Nicole Händel |
| author_facet | Henriette Edemann-Callesen Henning Keinke Andersen Anja Ussing Anne Virring Poul Jennum Nanette Mol Debes Torben Laursen Lone Baandrup Christina Gade Jette Dettmann Jonas Holm Camilla Krogh Kirsten Birkefoss Simon Tarp Mina Nicole Händel |
| author_sort | Henriette Edemann-Callesen |
| collection | DOAJ |
| description | Summary: Background: Melatonin prescriptions for children and adolescents have increased substantially during the last decade. Existing clinical recommendations focus on melatonin as a treatment for insomnia related to neurodevelopmental disorders. To help guide clinical decision-making, we aimed to construct a recommendation on the use of melatonin in children and adolescents aged 5–20 years with idiopathic chronic insomnia. Methods: A systematic search for guidelines, systematic reviews and randomised controlled trials (RCT) were performed in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A search for adverse events in otherwise healthy children and adolescents was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 18, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (5–20 years of age) with idiopathic chronic insomnia, in whom sleep hygiene practices have been inadequate and melatonin was tested. There were no restrictions on dosage, duration of treatment, time of consumption, or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, all-cause dropouts, and non-serious adverse events. Outcomes were assessed at different time points to assess short-term and long-term effects. Meta-analysis was performed using inverse variance random-effects model and risk of bias was assessed using Cochrane risk of bias tool. If possible, funnel plots would be constructed to investigate publication bias. Heterogeneity was calculated via I2 statistics. A multidisciplinary guideline panel formulated the recommendation according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was subsequently used to discuss the feasibility and acceptance of the constructed recommendation alongside the impact on resources and equity. The protocol is registered with the Danish Health Authority. Findings: We included eight RCTs with 419 children and adolescents with idiopathic chronic insomnia. Melatonin led to a moderate increase in total sleep time by 30.33 min (95% confidence interval (CI) 18.96–41.70, 4 studies, I2 = 0%) and a moderate reduction in sleep latency by 18.03 min (95% CI −26.61 to −9.44, 3 studies, I2 = 0%), both as assessed by sleep diary. No other beneficial effects were found. None of the studies provided information on serious adverse events, yet the number of participants experiencing non-serious adverse events was increased (Relative risk 3.44, 95% CI 1.25–9.42, 4 studies, I2 = 0%). Funnel plots were not constructed due to the low number of studies. The certainty of evidence was very low on the quality of sleep and low for daytime functioning. Interpretation: Evidence of very low certainty shows that benefits are limited and unwanted events are likely when melatonin is used to treat otherwise healthy children and adolescents with chronic insomnia. Melatonin should never be the first choice of treatment for this particular population, yet carefully monitored short-term use may be considered if sleep hygiene practices and non-pharmacological interventions have proven inadequate, and only if daytime function is compromised. Funding: The Danish Health Authority and the Parker Institute, Bispebjerg and Frederiksberg Hospital supported by the Oak Foundation. |
| first_indexed | 2024-03-13T00:49:07Z |
| format | Article |
| id | doaj.art-1d042b052eea423190ddfc637417d649 |
| institution | Directory Open Access Journal |
| issn | 2589-5370 |
| language | English |
| last_indexed | 2024-03-13T00:49:07Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EClinicalMedicine |
| spelling | doaj.art-1d042b052eea423190ddfc637417d6492023-07-08T04:19:07ZengElsevierEClinicalMedicine2589-53702023-07-0161102048Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendationResearch in contextHenriette Edemann-Callesen0Henning Keinke Andersen1Anja Ussing2Anne Virring3Poul Jennum4Nanette Mol Debes5Torben Laursen6Lone Baandrup7Christina Gade8Jette Dettmann9Jonas Holm10Camilla Krogh11Kirsten Birkefoss12Simon Tarp13Mina Nicole Händel14The Danish Health Authority, 2300, Copenhagen, Denmark; Centre for Evidence-Based Psychiatry, Psychiatric Research Unit, Psychiatry Region Zealand, 4200, Slagelse, Denmark; Corresponding author. The Danish Health Authority, 2300, Copenhagen, Denmark.The Danish Health Authority, 2300, Copenhagen, DenmarkThe Danish Health Authority, 2300, Copenhagen, DenmarkDepartment of Child and Adolescent Psychiatry, Aarhus University Hospital, Psychiatry, Aarhus, DenmarkDanish Centre for Sleep Medicine, Department of Clinical Neurophysiology, Rigshospitalet, Copenhagen, DenmarkDepartment of Pediatrics, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical Pharmacology, Aarhus University Hospital, DenmarkDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Bispebjerg and Gentofte Departments, Mental Health Centre Copenhagen, Copenhagen University Hospital – the Mental Health Services of the Capital Region in Denmark, DenmarkDepartments of Clinical Pharmacology and Clinical Medicine, Copenhagen University Hospital, Bispebjerg and Frederiksberg, University of Copenhagen, DenmarkDepartment of Pediatrics, Copenhagen University Hospital – NOH, Hillerød, DenmarkThe Occupational Therapist Association, DenmarkThe Danish Health Authority, 2300, Copenhagen, DenmarkThe Danish Health Authority, 2300, Copenhagen, DenmarkThe Danish Health Authority, 2300, Copenhagen, DenmarkThe Danish Health Authority, 2300, Copenhagen, Denmark; Research Unit OPEN, Department of Clinical Research, University of Southern Denmark, Odense, Denmark; The Parker Institute, Bispebjerg and Frederiksberg Hospital, Frederiksberg, DenmarkSummary: Background: Melatonin prescriptions for children and adolescents have increased substantially during the last decade. Existing clinical recommendations focus on melatonin as a treatment for insomnia related to neurodevelopmental disorders. To help guide clinical decision-making, we aimed to construct a recommendation on the use of melatonin in children and adolescents aged 5–20 years with idiopathic chronic insomnia. Methods: A systematic search for guidelines, systematic reviews and randomised controlled trials (RCT) were performed in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A search for adverse events in otherwise healthy children and adolescents was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 18, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (5–20 years of age) with idiopathic chronic insomnia, in whom sleep hygiene practices have been inadequate and melatonin was tested. There were no restrictions on dosage, duration of treatment, time of consumption, or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, all-cause dropouts, and non-serious adverse events. Outcomes were assessed at different time points to assess short-term and long-term effects. Meta-analysis was performed using inverse variance random-effects model and risk of bias was assessed using Cochrane risk of bias tool. If possible, funnel plots would be constructed to investigate publication bias. Heterogeneity was calculated via I2 statistics. A multidisciplinary guideline panel formulated the recommendation according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was subsequently used to discuss the feasibility and acceptance of the constructed recommendation alongside the impact on resources and equity. The protocol is registered with the Danish Health Authority. Findings: We included eight RCTs with 419 children and adolescents with idiopathic chronic insomnia. Melatonin led to a moderate increase in total sleep time by 30.33 min (95% confidence interval (CI) 18.96–41.70, 4 studies, I2 = 0%) and a moderate reduction in sleep latency by 18.03 min (95% CI −26.61 to −9.44, 3 studies, I2 = 0%), both as assessed by sleep diary. No other beneficial effects were found. None of the studies provided information on serious adverse events, yet the number of participants experiencing non-serious adverse events was increased (Relative risk 3.44, 95% CI 1.25–9.42, 4 studies, I2 = 0%). Funnel plots were not constructed due to the low number of studies. The certainty of evidence was very low on the quality of sleep and low for daytime functioning. Interpretation: Evidence of very low certainty shows that benefits are limited and unwanted events are likely when melatonin is used to treat otherwise healthy children and adolescents with chronic insomnia. Melatonin should never be the first choice of treatment for this particular population, yet carefully monitored short-term use may be considered if sleep hygiene practices and non-pharmacological interventions have proven inadequate, and only if daytime function is compromised. Funding: The Danish Health Authority and the Parker Institute, Bispebjerg and Frederiksberg Hospital supported by the Oak Foundation.http://www.sciencedirect.com/science/article/pii/S2589537023002250Children and adolescentsIdiopathicChronic insomniaMelatoninEvidence-based recommendation |
| spellingShingle | Henriette Edemann-Callesen Henning Keinke Andersen Anja Ussing Anne Virring Poul Jennum Nanette Mol Debes Torben Laursen Lone Baandrup Christina Gade Jette Dettmann Jonas Holm Camilla Krogh Kirsten Birkefoss Simon Tarp Mina Nicole Händel Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendationResearch in context EClinicalMedicine Children and adolescents Idiopathic Chronic insomnia Melatonin Evidence-based recommendation |
| title | Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendationResearch in context |
| title_full | Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendationResearch in context |
| title_fullStr | Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendationResearch in context |
| title_full_unstemmed | Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendationResearch in context |
| title_short | Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendationResearch in context |
| title_sort | use of melatonin in children and adolescents with idiopathic chronic insomnia a systematic review meta analysis and clinical recommendationresearch in context |
| topic | Children and adolescents Idiopathic Chronic insomnia Melatonin Evidence-based recommendation |
| url | http://www.sciencedirect.com/science/article/pii/S2589537023002250 |
| work_keys_str_mv | AT henrietteedemanncallesen useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT henningkeinkeandersen useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT anjaussing useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT annevirring useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT pouljennum useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT nanettemoldebes useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT torbenlaursen useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT lonebaandrup useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT christinagade useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT jettedettmann useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT jonasholm useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT camillakrogh useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT kirstenbirkefoss useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT simontarp useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext AT minanicolehandel useofmelatonininchildrenandadolescentswithidiopathicchronicinsomniaasystematicreviewmetaanalysisandclinicalrecommendationresearchincontext |