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Eric Konofal,1,2 Wei Zhao,3–5 Cédric Laouénan,5–7 Michel Lecendreux,1,2 Florentia Kaguelidou,3–5 Lila Benadjaoud,4 France Mentré,5–7 Evelyne Jacqz-Aigrain3–51Pediatric Sleep Disorders Center, 2Child and Adolescent Psychiatric Department, 3Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, Assistance Publique – Hôpitaux de Paris (APHP), 4Clinical Investigation Center, Institut National de la Santé et de la Recherche Médicale (INSERM), 5Université Paris Diderot, Sorbonne Paris Cité, Paris, 6INSERM, Infection, Antimicrobiens, Modélisation, Evolution (IAME), UMR1137, Paris, 7Department of Biostatistiques, Hôpital Bichat, APHP, Paris, FranceObjective: Mazindol has been proposed as a potential treatment of children with attention deficit/hyperactivity disorder (ADHD). The purpose of this pilot study was to assess its pharmacokinetics, short-term efficacy, and safety.Subjects and methods: A total of 24 children (aged 9–12 years) with ADHD (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text-revision criteria) received a daily dose of 1 mg for 7 days and were followed for 3 additional weeks. Pharmacokinetic samples were collected after the first administration. ADHD symptoms were assessed using the ADHD Rating Scale (RS)-IV, Conners’ Parent Rating Scale – Revised: Long (CPRS-R:L) at screening, baseline, and the end of the study. The Clinical Global Impression – Severity (CGI-S) scale was assessed at baseline, and the CGI – Improvement (CGI-I) scale was assessed at subsequent visits.Results: Twenty-one subjects (aged 10±1 years) were analyzed. Pharmacokinetic data were described by a one-compartment model with first-order absorption, elimination, and lag time. The typical apparent clearance and apparent volume of distribution were 27.9 L/h and 234 L, and increased with fat-free mass and age, respectively. The mean change in score in ADHD RS-IV after 1 week of mazindol was −24.1 (P

Since 1970, a certain number of studies have reported sleep disturbances in children with ADHD. Data from questionnaires and parental reports showed behavioural difficulties occurring at wake-sleep transition such as bed-time refusal, delayed sleep-onset, early awakenings, suggesting the occurrence of specific abnormalities in the mechanisms of alertness maintainance.Few polysomnographic studies have been conducted in ADHD children considering the prevalence and the importance of the disorder in the field of child psychopathology. The majority of these studies produced heterogenous and conflicting data and no clear abnormalities of non-rapid eye movement or REM sleep were found.Polysomnographic data, however supports the evidence of sleep-wake-transition abnormalities in ADHD children. Modifications in sleep-onset-latencies, number of stage shifts, have previously been reported using all-night polysomnography.One study performed Multiple latency tests in ADHD children and concluded that ADHD had daytime sleep abnormalities when compared with controls.One other important issue concerns motor activity during sleep in hyperactive children which was found to be increased in studies using actigraphy or video analysis. These findings could lead to important clinical and therapeutic applications as stimulants could help to normalise sleep or motor behaviour during sleep in some ADHD children. [Copyright &y& Elsevier]

A 3-year-old child was referred to consultation for hyperactivity, attention deficit, impulsivity, and sleep problems. He met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for attention-deficit/hyperactivity disorder. At baseline, the Conners' Parent Rating Scale and the Conners' Teacher Rating Scale raw total scores were 30 and 32, respectively. The child had low a serum ferritin level (13 ng/mL). After 8 months of treatment with Tardyferon (ferrous sulfate, 80 mg/day), his serum ferritin increased to 102 ng/mL. Both parents and teachers reported considerable behavioral improvement. The Conners' Parent and Teacher Rating Scale raw total scores decreased to 19 and 13, respectively. This is the first report of the effectiveness of iron supplementation in a young child with attention-deficit/hyperactivity disorder. [ABSTRACT FROM AUTHOR]

Objective: To perform a meta-analysis of subjective (i.e., based on questionnaires) and objective (i.e., using polysomnography or actigraphy) studies comparing sleep in children with attention-deficit/hyperactivity disorder (ADHD) versus controls.Method: We searched for subjective and objective sleep studies (1987-2008) in children with ADHD (diagnosed according to standardized criteria). Studies including subjects pharmacologically treated or with comorbid anxiety/depressive disorders were excluded.Results: Sixteen studies, providing 9 subjective and 15 objective parameters and including a total pooled sample of 722 children with ADHD versus 638 controls, were retained. With regard to subjective items, the meta-analysis indicated that children with ADHD had significantly higher bedtime resistance (z = 6.94, p <.001), more sleep onset difficulties (z = 9.38, p <.001), night awakenings (z = 2.15, p =.031), difficulties with morning awakenings (z = 5.19, p <.001), sleep disordered breathing (z = 2.05, p =.040), and daytime sleepiness (z = 1.96, p =.050) compared with the controls. As for objective parameters, sleep onset latency (on actigraphy), the number of stage shifts/hour sleep, and the apnea-hypopnea index were significantly higher in the children with ADHD compared with the controls (z = 3.44, p =.001; z = 2.43, p =.015; z = 3.47, p =.001, respectively). The children with ADHD also had significantly lower sleep efficiency on polysomnography (z = 2.26, p =.024), true sleep time on actigraphy (z = 2.85, p =.004), and average times to fall asleep for the Multiple Sleep Latency Test (z = 6.37, p <.001) than the controls.Conclusions: The children with ADHD are significantly more impaired than the controls in most of the subjective and some of the objective sleep measures. These results lay the groundwork for future evidence-based guidelines on the management of sleep disturbances in children with ADHD. [ABSTRACT FROM AUTHOR]

The history of narcolepsy research began with the pioneering work of Jean-Baptiste-Édouard Gélineau in the late 19th century. In the 1880s, Gélineau introduced the term "narcolepsy" to describe a condition characterized by sudden and uncontrollable episodes of sleep. His clinical descriptions laid the foundation for our understanding of this complex disorder. Over the last half-century, the pharmacological landscape for narcolepsy treatment has evolved remarkably, shifting from merely managing symptoms to increasingly targeting its underlying pathophysiology. By the 1930s, treatments such as ephedrine and amphetamine were introduced to alleviate excessive daytime sleepiness, marking significant advancements in narcolepsy management. These stimulants provided temporary relief, helping patients maintain wakefulness during the day. As research progressed, the focus shifted towards understanding the disorder's underlying mechanisms. The discovery of orexin (also known as hypocretin) in the late 1990s revolutionized the field. This breakthrough underscored the importance of orexin in regulating sleep-wake cycles and provided new targets for pharmacological intervention. Looking ahead, the future of narcolepsy pharmacotherapy is poised for further innovation. The ongoing exploration of orexin receptor agonists and the potential development of neuroprotective therapeutic targets underscore a promising horizon. Emerging research into the genetic and immunological underpinnings of narcolepsy opens new avenues for personalized medicine approaches and the identification of biomarkers for more precise treatment strategies. Additionally, the refinement of existing treatments through improved delivery systems and the investigation of combination therapies offer opportunities for enhanced efficacy and improved quality of life for patients with narcolepsy., Competing Interests: Declaration of competing interest The author (E.K.) declares no conflicts of interest, except for serving as a Chief Scientific Officer for NLS Pharmaceutics, holding a directorship at Aexon Labs, and being listed as an inventor on patents mentioned in the manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: NLS-3 or (R, R) enantiomer of phacetoperane (levophacetoperane) is the reverse ester of methylphenidate, a well-documented psychostimulant marketed for the treatment of attention-deficit/hyperactivity disorder (ADHD) since the end of 1950s. Launched in Canada and Europe by Specia Rhône-Poulenc and Rhodia, marketed as Lidepran® (8228 R.P.), for the treatment of obesity and depression, phacetoperane became an increasingly popular psychiatric medication from 1959 to 1967. Previous data supported that the stimulant effect of phacetoperane differed from those of other medications acting on the catecholamine system (e.g., methylphenidate, amphetamine), with an advantage of benefit/risk balance., Method: The goal of this study is to characterize the binding profile of NLS-3 using in vitro and in vivo assays and hypothesize potential therapeutic uses considering all available data., Results: A complete binding profile assay confirmed the potential benefit of phacetoperane with a higher benefit/risk compared to other stimulants. NLS-3 synthesis resulted from phenylketone, which is also used for the synthesis of methylphenidate. It differs from that used by Rhône-Poulenc SA laboratories, allowing the possibility of individualizing several enantiomers not synthesized previously. The present review also confirmed extensive clinical use of the compound in almost one thousand children and adolescents in large dose ranges with fewer side effects versus comparative treatments. Furthermore, levophacetoperane was found to be generally well-tolerated by the subjects., Conclusion: NLS-3 could be a safer and more potent alternative to stimulants for patients with ADHD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Symptoms of attention-deficit/hyperactivity disorder (ADHD) and sleep disturbances frequently co-occur, and can result in significant functional impairments that worsen quality of life. Despite a growing number of studies focusing on the association between sleep disturbances and ADHD symptoms over the last 20 years, the directionality of this association from childhood to early adulthood remains unclear., Method: A sample of French parents (n = 1,055) were followed-up over a 9-year period. At children mean ages of 9, 13, and 18 years, parents were interviewed about their children's ADHD symptoms and sleep disturbances. Random-intercept cross-lagged panel models assessed the directionality of the association from childhood to early adulthood., Results: Parent-reported sleep disturbances at a mean age of 13 years predicted increased ADHD symptoms 5 years later. Additional analyses suggested that this effect might be limited to inattentive symptoms, and that ADHD symptoms at a mean age of 9 predicted increased sleep disturbances 4 years later., Conclusion: The present study provides evidence of a directional longitudinal association between parent-reported sleep disturbances and ADHD symptoms from adolescence to early adulthood. Our results highlight the importance of identifying sleep disturbances and ADHD symptoms for the design of preventive interventions. Future studies investigating this association in children with a clinical diagnosis of ADHD have the potential to provide important information for clinical practice., (Copyright © 2022 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Study Objectives: The goal of the current study was to explore the effect of a 2-month quarantine on children and adolescents with narcolepsy and to describe the changes in their sleep, mood, and metabolism during this period., Methods: The study involved 77 patients aged 7 to 23 years with a diagnosis of narcolepsy. Participants had to answer multiple-choice questions to characterize the changes and modifications in their own habits and state of health., Results: Participants reported changes in daytime sleep, nighttime sleep schedules, treatment intake, food intake, weight, and amount of screen time. Most patients reported deterioration in their memory and attention abilities as well as a decrease in their work efficiency. Mood appeared to be less affected, although it deteriorated in less than one-third of the participants who reported feeling sad more often., Conclusions: The prolonged and complete lockdown seemed to have an effect on children and adolescents with narcolepsy, and changes are often considered by the participants to depend on or to determine an overall quality of adaptation to the situation. This study highlights the importance of maintaining and strengthening time markers in individuals with narcolepsy and should help to establish guidelines that would apply in future quarantine situations., Citation: de Laclause AP, Konofal E, Bokov P, Delclaux C, Lecendreux M. Adjustment to lockdown in children and adolescents with narcolepsy in France. J Clin Sleep Med . 2022;18(9):2247-2252., (© 2022 American Academy of Sleep Medicine.)