International Expert Opinions and Recommendations on the Use of Melatonin in the Treatment of Insomnia and Circadian Sleep Disturbances in Adult Neuropsychiatric Disorders.

Laura Palagini,Claudio Mencacci,Raffaele Manni,Mario Amore,Sylvie Royant Parola,Roberto Brugnoli,Pierre A Geoffroy,Antonino Minervino,Giuseppe Plazzi,Paolo Girardi,Lino Nobili,Luigi Grassi,Julia Maruani,Eugenio Aguglia,Régis Lopez,Stéphanie Bioulac,Giovanni Biggio,Pierre Philip,Patrice Bourgin,Jean‐Arthur Micoulaud‐Franchi ,I Poirot ,Carmen Schröder

doi:10.3389/fpsyt.2021.688890

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.

Highlights

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
Thirteen articles were considered for mood disorders, 1 for attention deficit hyperactivity disorders (ADHDs) in adults, 1 for autism spectrum disorders (ASD) in adults, 5 for delirium, 7 for neurocognitive disorders, 6 for schizophrenia, 2 for substance use disorders, and no studies for anxiety and eating disorders (Figure 1)
PR melatonin at 2 mg is recommended in the treatment of insomnia in healthy aging [8, 9] 2 mg of PR or 3– 6 mg of IR melatonin should be useful in the treatment of sleep disturbances in Neurocognitive Disorder

Summary

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. Alterations in circadian rhythm are considered risk factors for the onset of psychiatric disorders, precursors of relapse, associated with residual symptoms, treatment resistance, and increased suicidal risk. Patients with psychiatric disorders and circadian sleep disorders may present polymorphisms of different circadian clock genes and mutations in melatonin receptors, which may alter the biological clock [13, 14]. These findings suggested that, as for insomnia, altered circadian rhythms might be important modifiable risk factors to prevent psychiatric disorders and/or achieve and maintain remission. Melatonin can be used as a treatment for benzodiazepines and hypnotics discontinuation in patients with insomnia [15]

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