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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

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.)

A combination of noradrenergic and antimuscarinic agents reduces the apnea-hypopnea index (AHI) in adult patients with obstructive sleep apnoea (OSA) via reduced upper airway collapsibility, suggesting that a shift in the sympathovagal balance improves OSA. The objectives of our present case-control study were to assess heart rate variability (HRV) indices in the stages of sleep in children with and without OSA to evaluate OSA-induced sleep HRV modifications and to assess whether increased collapsibility measured during wakefulness is associated with reduced sympathetic activity during non-rapid eye movement (NREM) sleep. Three groups of 15 children were matched by sex, age, z-score of body mass index and ethnicity: non-OSA (obstructive AHI [OAHI] <2 events/hr), mild (OAHI ≥2 to <5 events/hr) or moderate-severe (OAHI ≥5 events/hr) OSA. Pharyngeal compliance was measured during wakefulness using acoustic pharyngometry. HRV indices (time and frequency domain variables) were calculated on 5-min electrocardiography recordings from polysomnography during wakefulness, NREM and REM sleep in periods free of any event. As compared to children without OSA, those with OSA (n = 30) were characterised by increased compliance and no physiological parasympathetic tone increase in REM sleep. Children with increased pharyngeal compliance (n = 21) had a higher OAHI due to higher AHI in NREM sleep, whereas their sympathetic tone was lower than that of those with normal compliance (n = 24). In conclusion, children with increased pharyngeal compliance exhibit decreased sympathetic tone associated with increased AHI in NREM sleep. Therapeutics directed at sympathovagal balance modifications should be tested in childhood OSA., (© 2021 European Sleep Research Society.)

Study Objectives: We aimed to assess ventilatory control in typically developing children with and without obstructive sleep apnea (OSA)., Methods: Otherwise healthy children referred for suspicion of OSA were recruited. In addition to polysomnography, we analyzed loop, controller and plant gains (ie, LG, CG, and PG), which reflect the stability of control, chemoreceptor sensitivity and the pulmonary control of blood gases in response to changes in ventilation, respectively, from tidal breathing recordings during wakefulness. Two bivariate (ventilation, end-tidal CO 2 : one unconstrained and one constrained) and one trivariate (plus end-tidal oxygen) unconstrained model were used to assess model consistency and oxygen chemosensitivity., Results: In sum, 54 children (median age 11.6 years) were included. Children with OSA (n = 19, [obstructive apnea-hypopnea index] OAHI ≥2.h -1 ) had a higher plant gain compared with those without OSA (n = 35), and it was positively correlated with apnea hypopnea index (AHI) (r 2  = 0.10, p < 0.020). The two models showed consistent results. The bivariate constrained model showed that children with OAHI ≥5.h -1 showed an increased steady-state plant gain compared with children with OAHI <5.h -1 . The trivariate model did not show evidence of any abnormality of oxygen chemosensitivity., Conclusion: Plant gain may contribute to OSA pathophysiology in children, and therapies directed at its reduction should be tested., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Our objective was to evaluate the usefulness of acoustic pharyngometry and rhinometry in assessing obstructive sleep apnea (OSA) syndrome in children., Patients/methods: Patients who were hospitalized for polysomnography underwent acoustic pharyngometry and rhinometry in sitting and supine positions to measure anatomical (pharyngeal and nasopharyngeal) volumes and collapsibility characteristics (reduction of pharyngeal volume, estimated pharyngeal compliance, and reduction of nasopharyngeal volume)., Results: In this study, we prospectively enrolled 103 children (median age, 10.4 years; 47 girls). Measures obtained from rhinometry correlated with height and were further height-normalized whereas measures obtained from pharyngometry did not correlate with height. Sleep apnea was ruled out in 51 subjects, while 52 children fulfilled OSA criteria (35 with obstructive apnea-hypopnea index ≥ 2 and < 5.h -1 [mild] and 17 with an index ≥ 5). The three groups differed on the z-score of BMI, the reduction of pharyngeal volume when supine, the estimated pharyngeal compliance and the supine normalized nasopharyngeal volume. These four factors linearly correlated with the apnea index even though children without OSA and mild OSA were found to be similar overall. A multivariate analysis with apnea index as the dependent variable and BMI z-score, neck circumference, mean pharyngeal area in supine position, estimated pharyngeal compliance and normalized nasopharyngeal volume as independent variables, showed that only BMI z-score and estimated compliance remained independent predictors of obstructive apnea (r 2 value = 0.25, p < 0.0001)., Conclusion: An increase in pharyngeal compliance is an independent risk factor of OSA syndrome in children; it can be measured using acoustic pharyngometry while awake., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Prior follow-up studies of attention-deficit/hyperactivity disorder (ADHD) have mostly been from North America. They have provided a good deal of information about ADHD, but whether these results generalize to population samples and to other countries is not certain. Most prior studies have also not assessed predictors of possible new onsets of ADHD in non-ADHD youth or the validity of subthreshold forms of the disorder., Methods: 1,012 families were recruited at baseline, when a telephone interview assessed a child in the 6-12 years age range. The interview covered symptoms of ADHD, conduct disorder, and oppositional defiant disorder as well as family living situation, school performance, sleep disturbance, eating habits, use of supplemental iron, and history of ADHD treatment. Nine years later, the persistence of ADHD and its impairments and the emergence of new conditions were assessed. DSM-5 diagnostic criteria were used to diagnose ADHD., Results: 492 of the 1,012 participants seen at baseline were followed up 9 years later, at a mean age of 18 years. At follow-up, 16.7% of the children diagnosed with ADHD at baseline met full criteria for ADHD and 11.1% met criteria for subthreshold ADHD, yielding a persistence rate of 27.8%. Among children not diagnosed with ADHD at baseline, 1.1% met criteria for ADHD at follow-up. The persistence of ADHD and new onsets of ADHD were predicted by several baseline clinical features and by a family history of ADHD., Conclusions: We replicated predictors of the persistence of ADHD found in prior studies and provide new data about predictors of new ADHD onsets in the population. Our findings about subthreshold ADHD support a dimensional conceptualization of the disorder, highlighting the potential clinical utility of a subthreshold diagnostic category. This study also contributes to the ongoing debate regarding adult-onset ADHD., (© Copyright 2019 Physicians Postgraduate Press, Inc.)

Background: Behavioural interventions are recommended for use with children and young people with attention deficit hyperactivity disorder (ADHD); however, specific guidance for their implementation based on the best available evidence is currently lacking., Methods: This review used an explicit question and answer format to address issues of clinical concern, based on expert interpretation of the evidence with precedence given to meta-analyses of randomised controlled trials., Results: On the basis of current evidence that takes into account whether outcomes are blinded, behavioural intervention cannot be supported as a front-line treatment for core ADHD symptoms. There is, however, evidence from measures that are probably blinded that these interventions benefit parenting practices and improve conduct problems which commonly co-occur with ADHD, and are often the main reason for referral. Initial positive results have also been found in relation to parental knowledge, children's emotional, social and academic functioning - although most studies have not used blinded outcomes. Generic and specialised ADHD parent training approaches - delivered either individually or in groups - have reported beneficial effects. High-quality training, supervision of therapists and practice with the child, may improve outcomes but further evidence is required. Evidence for who benefits the most from behavioural interventions is scant. There is no evidence to limit behavioural treatments to parents with parenting difficulties or children with conduct problems. There are positive effects of additive school-based intervention for the inattentive subtype. Targeting parental depression may enhance the effects of behavioural interventions., Conclusions: Parent training is an important part of the multimodal treatment of children with ADHD, which improves parenting, reduces levels of oppositional and noncompliant behaviours and may improve other aspects of functioning. However, blinded evidence does not support it as a specific treatment for core ADHD symptoms. More research is required to understand how to optimise treatment effectiveness either in general or for individual patients and explore potential barriers to treatment uptake and engagement. In terms of selecting which intervention formats to use, it seems important to acknowledge and respond to parental treatment preferences., (© 2017 Association for Child and Adolescent Mental Health.)

Psychostimulants are used for the treatment of excessive daytime sleepiness in a wide range of sleep disorders as well as in attention deficit hyperactivity disorder or cognitive impairment in neuropsychiatric disorders. Here, we tested in mice the wake-promoting properties of NLS-4 and its effects on the following sleep as compared with those of modafinil and vehicle. C57BL/6J mice were intraperitoneally injected with vehicle, NLS-4 (64 mg/kg), or modafinil (150 mg/kg) at light onset. EEG and EMG were recorded continuously for 24 h after injections and vigilance states as well as EEG power densities were analyzed. NLS-4 at 64 mg/kg induced significantly longer wakefulness duration than modafinil at 150 mg/kg. Although no significant sleep rebound was observed after sleep onset for both treatments as compared with their vehicles, modafinil-treated mice showed significantly more NREM sleep when compared to NLS-4. Spectral analysis of the NREM EEG after NLS-4 treatment indicated an increased power density in delta activity (0.75-3.5 Hz) and a decreased power in theta frequency range (6.25-7.25 Hz), while there was no differences after modafinil treatment. Also, time course analysis of the delta activity showed a significant increase only during the first 2 time intervals of sleep after NLS-4 treatment, while delta power was increased during the first 9 time intervals after modafinil. Our results indicate that NLS-4 is a highly potent wake-promoting drug with no sign of hypersomnia rebound. As opposed to modafinil, recovery sleep after NLS-4 treatment is characterized by less NREM amount and delta activity, suggesting a lower need for recovery despite longer drug-induced wakefulness.

Background: Mazindol is under investigation for the treatment of attention-deficit/hyperactivity disorder (ADHD) because of its alertness-enhancing properties. A novel controlled-release (CR) formulation of mazindol was developed to allow once-daily dosing., Objective: The aim of this study was to evaluate the efficacy of mazindol CR in adults with ADHD., Design: We conducted a randomized, double-blind, placebo-controlled 6-week trial., Methods: Subjects diagnosed with ADHD using the Mini-International Neuropsychiatric Structured Interview (MINI) and with an ADHD Rating Scale, Diagnostic and Statistical Manual of Mental Disorders 5th Edition (ADHD-RS-DSM5) score ≥ 28 were randomized to receive placebo or 1-3 mg/day of mazindol for 6 weeks. The primary endpoint was the reduction from baseline in the ADHD-RS-DSM5 score on Day 42. Secondary endpoints were response rates defined by change in ADHD-RS-DSM5 (≥ 30 or ≥ 50% reduction) and dichotomized Clinical Global Impression-Improvement (CGI-I) score (1 or 2). An exploratory endpoint of functional impairment, as measured by the Target Impairment Scale, examined individualized deficits in specific settings. Safety, tolerability, and pharmacokinetics were assessed., Results: Eighty-five participants were randomized (n = 43 active, 42 placebo); 75 completed. Weekly ADHD-RS-DSM5 measurements after mazindol differed from placebo beginning at Day 7, with a least squares mean difference (active-placebo) of - 13.2 at Day 42 and an effect size of 1.09. For the 30% or more reduction in ADHD-RS-DSM5 (minimal response), a significant difference (active-placebo) was seen starting at Day 7 and continuing to Day 42. For the CGI-I (1 or 2) and for the 50% or more reduction in ADHD-RS-DSM5 (measures of excellent response), the differences began at Day 14 and continued to Day 42. Functional impairment was significantly different in the proportion achieving at least a 50% reduction in target impairment score (42.9% mazindol vs 11.9% placebo) by Day 42. Dry mouth, nausea, fatigue, heart rate (HR) increased, decreased appetite, and constipation were more prevalent for mazindol versus placebo. Overall, mazindol CR had minimal effects on blood pressure and small effects on HR., Conclusion: Mazindol CR was efficacious in the treatment of adults with ADHD, with a large effect size, and was well tolerated, supporting the progression to phase III. (Clinicaltrials.gov Registration No. NCT02808104).

Mazindol is an imidazo-isoindole derivative, a tricyclic compound and a non-amphetamine central nervous system stimulant that blocks dopamine and norepinephrine reuptake. Mazindol was withdrawn from the US and European markets in 1999 for reasons unrelated to its efficacy or safety around a time when other anorexic drugs were found to be associated with the development of pulmonary arterial hypertension (PAH). Despite the use of mazindol for decades, reports of PAH due to mazindol intake have been extremely rare. Recent interest on mazindol has emerged for the treatment of narcolepsy and attention-deficit/hyperactivity disorder. Therefore, an updated understanding of the potential benefits and risks of mazindol in these patient populations is warranted., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Psychostimulants are the recommended first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD). Methylphenidate is one of the most commonly used psychostimulants worldwide. Given that immediate-release and/or tablet/capsule formulations may decrease adherence to methylphenidate treatment, several drug companies have been developing novel long-acting and/or liquid/chewable formulations that may improve adherence as well as (for long-acting formulations) reduce abuse potential, decrease stigma associated with multiple administrations per day, and decrease the potential for adverse effects related to dosage peak. Here, we review the pharmacokinetics, efficacy, and tolerability of novel formulations of methylphenidate that are in development or have been approved by the US FDA or European Medicines Agency (EMA) in the last 5 years. We searched the websites of the FDA, EMA, ClinicalTrials.gov, and the pertinent drug companies. We also searched PubMed, Ovid databases (MEDLINE, PsycINFO, Embase + Embase classic), and ISI Web of Knowledge (Web of Science [Science Citation Index Expanded], Biological Abstracts, Biosis, Food Science and Technology Abstracts) to retrieve any additional pertinent information. We found data from trials for the following compounds: (1) methylphenidate extended-release oral suspension (MEROS; NWP06, Quillivant™); (2) methylphenidate extended-release chewable capsules (NWP09, QuilliChew ER™); (3) methylphenidate hydrochloride extended-release capsules (Aptensio XR™); (4) methylphenidate extended-release orally disintegrating tablets (XR-ODT; NT-0102, Cotempla™); (5) ORADUR technology (once-daily tamper-resistant formulation) methylphenidate sustained release (SR); and (6) methylphenidate modified-release (HLD-200; Bejorna™). Overall, available evidence based on trials suggests these compounds have good efficacy and tolerability. Future research should further explore the effectiveness and tolerability of these new formulations as well as their potential to improve adherence to treatment in the 'real world' via pragmatic trials.

Parents of children with ADHD are more likely to present the disorder, which can affect quality of life and parenting strategies. Few studies have examined parental ADHD to date, none in France. Prevalence of self-rated ADHD symptoms in adulthood and childhood was estimated among 60 biological mothers or fathers of children with confirmed ADHD in France. Cutoffs were total score ≥46 on the Wender Utah Rating Scale and ≥4 on the Adult ADHD Self-Report Scale Screener. Results indicated possible child and adult ADHD in 12.5% of mothers and 10.0% of fathers. As these percentages exceed reported prevalence rates for the French population, a greater effort must be made to diagnose the disorder in parents.

Study Objectives: To evaluate the frequency, severity, and associations of symptoms of attention-deficit/hyperactivity disorder (ADHD) in children with narcolepsy with and without cataplexy., Design: Cross-sectional survey., Settings: Four French national reference centers for narcolepsy., Patients: One hundred eight consecutively referred children aged younger than 18 y with narcolepsy, with (NwC, n = 86) or without cataplexy (NwoC, n = 22), and 67 healthy controls., Interventions: The participants, their families, and sleep specialists completed a structured interview and questionnaires about sleep, daytime sleepiness, fatigue, and ADHD symptoms (ADHD-rating scale based upon Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [DSM-IV-TR] symptoms), and use of psychostimulants for the treatment of narcolepsy (administered in 68.2%). Polysomnographic measures were collected., Measurements and Results: Clinically significant levels of ADHD symptoms were found in 4.8% of controls compared with 35.3% in patients with NwoC (P < 0.001) and 19.7% in patients with NwC (P < 0.01). Total ADHD scores were 6.4 (95% confidence interval [CI]: 4.5, 9.0) in controls compared with 14.2 (95% CI: 10.6, 18.9; P < 0.001), in patients with NwoC and 12.2 (95% CI: 9.8, 15.3; P < 0.01) in patients with NwC; subscores of inattention and hyperactivity/impulsivity were also significantly higher in both narcolepsy groups compared with controls. No difference was found between the NwC and NwoC groups for any ADHD measure. ADHD symptom severity was associated with increased levels of sleepiness, fatigue, and insomnia. Compared with the 34 untreated patients, the 73 patients treated with psychostimulants (modafinil in 91%) showed a trend toward lower narcolepsy symptoms but not lower ADHD symptoms., Conclusions: Pediatric patients with narcolepsy have high levels of treatment-resistant attention-deficit/hyperactivity disorder (ADHD) symptoms. The optimal treatment for ADHD symptoms in these patients warrants further evaluation in longitudinal intervention studies., (© 2015 Associated Professional Sleep Societies, LLC.)

Background: Prior follow-up studies of attention-deficit/hyperactivity disorder (ADHD) ascertained ADHD cases in clinical samples mostly from North America but rarely from European countries. They have provided a good deal of information about the persistence of ADHD and its impairments, but the degree to which these results generalize to population samples and to other countries is not certain. Prior studies have also not assessed predictors of new-onset ADHD in youth without ADHD., Method: At baseline, 7,912 of 18 million telephone numbers were randomly selected from throughout France from October 2, 2008, through December 11, 2008. Among 4,186 eligible families, 1,012 (24.2%) were successfully recruited at baseline, when a telephone interview was administered to all families about a child in the 6- to 12-year age range. Four years later, we attempted to recruit the entire sample to assess the persistence of ADHD and its impairments and the emergence of new associated conditions., Results: 86.5% of the families assessed at baseline were followed-up (N = 875). Participants who were and were not interviewed at follow-up did not differ on any clinical or demographic features. At follow-up, the prevalence of full or subthreshold ADHD was 65.8% for ADHD participants and 9.8% for those not having ADHD at baseline. Among the children who were not diagnosed with ADHD at baseline, 3.4% were diagnosed with ADHD at follow-up. Both the persistence of ADHD and new onsets of ADHD were significantly predicted by several baseline clinical features and by having a family history of ADHD (all P values < .05)., Conclusions: We replicated prior predictors of ADHD's persistence and provide new data about predictors of new ADHD onsets in the population. Our data about subthreshold ADHD support a dimensional conceptualization of the disorder and address the potential clinical utility of a subthreshold diagnostic category., (© Copyright 2015 Physicians Postgraduate Press, Inc.)

Background: The efficacy of three dietary treatments for ADHD has been repeatedly tested in randomized controlled trials (RCTs). These interventions are restricted elimination diets (RED), artificial food colour elimination (AFCE) and supplementation with free fatty acids (SFFA). There have been three systematic reviews and associated meta-analyses of the RCTs for each of these treatments., Scope: The aim of this review is to critically appraise the studies on the dietary treatments of ADHD, to compare the various meta-analyses of their efficacy that have been published and to identify where the design of such RCTs could be improved and where further investigations are needed., Findings: The meta-analyses differ in the inclusion and exclusion criteria applied to potentially eligible studies. The range of average effect sizes in standard deviation units is RED (0.29-1.2), AFCE (0.18-0.42) and SFFA (0.17-0.31). The methodology of many of the trials on which the meta-analyses are based is weak., Conclusions: Nevertheless, there is evidence from well-conducted studies for a small effect of SFFA. Restricted elimination diets may be beneficial, but large-scale studies are needed on unselected children, using blind assessment and including assessment of long-term outcome. Artificial food colour elimination is a potentially valuable treatment but its effect size remains uncertain, as does the type of child for whom it is likely to be efficacious. There are additional dietary supplements that have been used with children with ADHD. A systematic search identified 11 RCTs that investigated the effects of these food supplements. Despite positive results for some individual trials, more studies are required before conclusions can be reached on the value in reducing ADHD symptoms of any of these additional supplements., (© 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.)

Objective: Nonpharmacological treatments are available for attention deficit hyperactivity disorder (ADHD), although their efficacy remains uncertain. The authors undertook meta-analyses of the efficacy of dietary (restricted elimination diets, artificial food color exclusions, and free fatty acid supplementation) and psychological (cognitive training, neurofeedback, and behavioral interventions) ADHD treatments., Method: Using a common systematic search and a rigorous coding and data extraction strategy across domains, the authors searched electronic databases to identify published randomized controlled trials that involved individuals who were diagnosed with ADHD (or who met a validated cutoff on a recognized rating scale) and that included an ADHD outcome., Results: Fifty-four of the 2,904 nonduplicate screened records were included in the analyses. Two different analyses were performed. When the outcome measure was based on ADHD assessments by raters closest to the therapeutic setting, all dietary (standardized mean differences=0.21-0.48) and psychological (standardized mean differences=0.40-0.64) treatments produced statistically significant effects. However, when the best probably blinded assessment was employed, effects remained significant for free fatty acid supplementation (standardized mean difference=0.16) and artificial food color exclusion (standardized mean difference=0.42) but were substantially attenuated to nonsignificant levels for other treatments., Conclusions: Free fatty acid supplementation produced small but significant reductions in ADHD symptoms even with probably blinded assessments, although the clinical significance of these effects remains to be determined. Artificial food color exclusion produced larger effects but often in individuals selected for food sensitivities. Better evidence for efficacy from blinded assessments is required for behavioral interventions, neurofeedback, cognitive training, and restricted elimination diets before they can be supported as treatments for core ADHD symptoms.

Objective: Mazindol is a tricyclic, anorectic, non-amphetamine stimulant used in narcolepsy and obesity since 1970. This study aimed to evaluate the long-term benefit/risk ratio in drug-resistant hypersomniacs and cataplexy sufferers., Methods: By retrospective analysis of the patients' files in the hospitals of Paris-Salpêtrière (n=91), Montpellier (n=40) and Lyon (n=8), the benefit (Epworth Sleepiness Score (ESS), cataplexy frequency, authorization renewal) and tolerance (side-effects, vital signs, electrocardiogram and cardiac echography) of mazindol were assessed., Results: The 139 patients (45% men) aged 36±15years (range: 9-74) suffered narcolepsy (n=94, 66% with cataplexy), idiopathic (n=37) and symptomatic hypersomnia (n=8) refractory to modafinil, methylphenidate and sodium oxybate. Under mazindol (3.4±1.3mg/day, 1-6mg) for an average of 30months, the ESS decreased from 17.7±3.5 to 12.8±5.1, with an average fall of -4.6±4.7 (p<0.0001) and the frequency of cataplexy fell from 4.6±3.1 to 2±2.8 episodes per week. The cataplexy was eliminated in 14.5% of patients, improved in 27.5%, and unchanged in 29% (missing data in 29%). The treatment was maintained long term in 83 (60%) patients, and stopped because of a lack of efficacy (22%) and/or secondary effects (9%). There was no pulmonary hypertension in the 45 patients who underwent a cardiac echography. The most common adverse effects were dry mouth (13%), palpitations (10%, including one with ventricular hyperexcitability), anorexia (6%), nervousness (6%) and headaches (6%)., Conclusion: Mazindol has a long-term, favorable benefit/risk ratio in 60% of drug-resistant hypersomniacs, including a clear benefit on cataplexy., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The authors systematically reviewed evidence on iron status, as well as studies of iron supplementation, in individuals with attention deficit/hyperactivity disorder (ADHD). PubMed, Ovid, EMBASE and Web of Knowledge were searched on 4 July 2012. Quantitative appraisal of trials was performed using Jadad's score. Most (n = 20) of the retrieved studies assessed an index of peripheral iron status (i.e., serum ferritin), with overall mixed results - that is, both significant and nonsignificant association between ADHD symptoms and serum ferritin levels. One MRI study reported significantly lower indices of thalamic iron in ADHD versus comparison subjects. Two trials, an open-label and a pilot randomized placebo-controlled study with high Jaded score (4), showed improvement in some but not all measures of ADHD symptoms. Three studies showed that children with ADHD plus sleep disorders, in particular restless legs syndrome, are at risk of iron deficiency. Finally, two studies suggested that iron deficiency might decrease the effectiveness of psychostimulant treatment. The authors discussed how the field could move from initial research mainly focused on serum ferritin towards a more comprehensive and translational investigation of iron in ADHD, with the potential to inform clinical practice in terms of screening and treating iron deficiency in individuals with ADHD.

Objective: Brain iron deficiency has been supposed to be involved in the pathophysiology of ADHD. Available studies assessing iron in ADHD are based on serum ferritin, a peripheral marker of iron status. To what extent serum ferritin correlates with brain iron (BI) is unclear. The main aim of this study was to compare BI, estimated with magnetic resonance imaging (MRI) in the putamen, pallidum, caudate, and thalamus, between children with and without ADHD. The secondary aim was to assess the correlation between serum ferritin and BI levels., Methods: Thirty-six children (18 with and 18 without ADHD, the latter including nine healthy controls and nine psychiatric controls) completed MRI and blood sampling. Brain iron levels were estimated by imaging T2*., Results: Children with ADHD showed significantly lower estimated BI in right and left thalamus compared to healthy controls. Estimated BI did not differ significantly between children with ADHD and psychiatric controls. Children with ADHD had significantly lower levels of serum ferritin than healthy as well as psychiatric controls. Serum ferritin and T2* values did not correlate significantly in most regions., Conclusions: Low iron in the thalamus may contribute to ADHD pathophysiology.

Background: Earlier studies point to the prevalence of attention deficit hyperactivity disorder (ADHD) to be similar around the world. There is, however, a wide variety in estimates. The prevalence of ADHD in youth has never been examined in France., Method: Starting with 18 million telephone numbers, 7,912 numbers are randomly selected. Among the 4,186 eligible families, 1,012 (24.2%) are successfully recruited. A telephone interview is administered to all families about a child in the 6 to 12 age range. It covered family living situation, school performance, symptoms of ADHD, conduct disorder (CD), and oppositional-defiant disorder (ODD), and other features of ADHD., Results: The prevalence of ADHD in France is between 3.5% and 5.6%. The population prevalence of treatment for ADHD is 3.5%. ADHD youth are more likely to be men than women, and, compared to non-ADHD children, ADHD children are more likely to have CD and ODD. Having ADHD is associated with a family history of the disorder. The ADHD youth are more likely to have had learning difficulties, to have repeated a grade, and to be functioning academically below grade level., Conclusions: The epidemiology of ADHD in French children is similar to the epidemiology of ADHD in other countries. The disorder occurs in between 3.5% to 5.6% of youth and is more common among boys than among girls. The authors replicate the well-known association of ADHD with CD, ODD, and indices of school failure. The impact of ADHD symptoms on school performance highlights the importance of screening for such symptoms in schools.

The characteristics of residual excessive sleepiness (RES), defined by an Epworth score >10 in adequately treated apnoeic patients, are unknown. 40 apnoeic patients, with (n = 20) and without (n = 20) RES, and 20 healthy controls underwent clinical interviews, cognitive and biological tests, polysomnography, a multiple sleep latency test, and 24-h sleep monitoring. The marked subjective sleepiness in the RES group (mean ± sd score 16.4 ± 3) contrasted with moderately abnormal objective measures of sleepiness (90% of patients with RES had daytime sleep latencies >8 min). Compared with patients without RES, the patients with RES had more fatigue, lower stage N3 percentages, more periodic leg movements (without arousals), lower mean sleep latencies and longer daytime sleep periods. Most neuropsychological dimensions (morning headaches, memory complaints, spatial memory, inattention, apathy, depression, anxiety and lack of self-confidence) were not different between patients with and without RES, but gradually altered from controls to apnoeic patients without and then with RES. RES in apnoeic patients differs markedly from sleepiness in central hypersomnia. The association between RES, periodic leg movements, apathy and depressive mood parallels the post-hypoxic lesions in noradrenaline, dopamine and serotonin systems in animals exposed to intermittent hypoxia.

Objective: To examine available literature regarding attention deficit hyperactivity disorder (ADHD) in adults., Methods: An electronic literature search of peer-reviewed English language articles using MEDLINE (without time limits) was undertaken., Results: Symptoms of ADHD in adults exert a substantial negative impact on daily life, including work, social life and relationships. Co-morbidities are common, further impairing quality of life. Diagnosis of adult ADHD can be difficult, as current criteria require evidence of symptom onset before the age of 7 years and impact on activities typically undertaken by children. Drug therapy is the first-line treatment for adult ADHD, particularly stimulant medication. However, methylphenidate (MPH) immediate-release tablets require three or more times daily dosing, which can impact on compliance, while demonstrating a loss of symptomatic benefit later in the day. Extended-release preparations of MPH, mixed amphetamine salts and dexamphetamine can provide symptom control for 6-12 h and the non-stimulant atomoxetine has demonstrated benefit in reducing ADHD symptoms. These therapies are generally well tolerated, but may be associated with adverse effects on the cardiovascular system, which need to be further assessed in controlled clinical trials. Psychological therapy may be beneficial in adults who continue to experience clinically significant symptoms while receiving pharmacotherapy., Conclusion: Further research in all areas of adult ADHD is urgently needed.

This paper, intended to provide useful insights for the clinical management of sleep disturbances in attention-deficit/hyperactivity disorder (ADHD), presents a critical, updated overview of the most relevant studies on the prevalence, etiopathophysiology and treatment strategies of sleep problems associated with ADHD, including restless legs syndrome, periodic limb movements in sleep, sleep-onset delay, increased nocturnal motor activity, sleep-disordered breathing, deficit in alertness, and sleep alterations accounted for by comorbid psychiatric disorders or ADHD medications. We also discuss some possible avenues for future research in the field., (Copyright 2010 Elsevier B.V. All rights reserved.)

Camptocormia (a flexion of the trunk that only appears when standing or walking) affects a minority of patients with Parkinson's disease (PD). As it responds poorly to levodopa and is associated with reduced midbrain and pons volume, it may result from non-dopaminergic, brainstem lesions. As several sleep abnormalities in PD also result from non-dopaminergic brainstem lesions, we monitored sleep in 24 non-demented PD patients with (n = 12) and without (n = 12) camptocormia and in 12 controls. Nearly half (42%) patients with camptocormia had abnormal periodic leg movement indices (>15/h), versus 17% patients without camptocormia and 8% of controls (p = 0.02). In addition, the percentage of enhanced muscle activity during REM sleep (measured on the chin and on the limb muscles) tended to be higher in patients with than without camptocormia (51 +/- 39% vs. 20 +/- 25%, p = 0.06). The other sleep and REM sleep characteristics (sleep and REM sleep onset latencies, sleep time and sleep stage percentages, REMs density, arousal, and apnea-hypopnea indices) were not different between these two PD groups. Lesions causing this axial dystonia may spare the sleep systems but affect the control of movements during sleep., ((c) 2009 Movement Disorder Society.)

Parkin gene mutations cause a juvenile parkinsonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied. The aim of this study was to evaluate the sleep-wake phenotype in patients with two parkin mutations, compared with patients with idiopathic Parkinson's disease (iPD). Sleep interview and overnight video-polysomnography, followed by multiple sleep latency tests, were assessed in 11 consecutive patients with two parkin mutations (aged 35-60 years, from seven families) and 11 sex-matched patients with iPD (aged 51-65 years). Sleep complaints in the parkin group included insomnia (73% patients versus 45% in the iPD group), restless legs syndrome (45%, versus none in the iPD group, P = 0.04), and daytime sleepiness (45%, versus 54% in the iPD group). Of the parkin patients, 45% had REM sleep without atonia, but only 9% had a definite REM sleep behavior disorder. All sleep measures were similar in the parkin and iPD groups. Two parkin siblings had a central hypersomnia, characterized by mean daytime sleep latencies of 3 min, no sleep onset REM periods, and normal nighttime sleep. Although the patients with two parkin mutations were young, their sleep phenotype paralleled the clinical and polygraphic sleep recording abnormalities reported in iPD, except that restless legs syndrome was more prevalent and secondary narcolepsy was absent.