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Article Dans Une Revue L'Encéphale Année : 2022

Therapeutic approaches for sleep and rhythms disorders in children with ASD

Approches thérapeutiques des troubles du sommeil et des rythmes chez l’enfant avec TSA

Résumé

Sleep disturbances are extremely common (40–86%) in children and adolescents, especially those with autism spectrum disorders (ASD) and are often among the first symptoms identified by parents at a very early stage of their child's development. These abnormalities are among the main parental concerns when having a child with ASD and have a significant impact on the quality of life of patients, their parents, and more broadly their siblings. Sleep disorders are essentially abnormalities of the sleep-wake rhythm – primarily sleep onset insomnia or nocturnal awakenings (with difficulty falling back to sleep). These disturbances can be accompanied by other sleep disorders, requiring notably a systematic elimination of the presence of a sleep apnea or restless legs syndrome – to ensure a personalized and efficient therapeutic approach. Physiologically, the determinants of these sleep disorders are poorly understood, even though several studies point to a significant decrease in melatonin synthesis in people with ASD. Melatonin is a hormone that facilitates falling asleep and maintaining sleep and is also involved in the endogenous synchronization of internal biological clocks. However, the causal factors of this decrease in melatonin synthesis are largely unknown, involving to a small extent the genes involved in melatonin synthesis pathway. The treatment of sleep disorders is relatively systematic: after eliminating other specific sleep disorders associated with the complaint of insomnia, as well as other possible associated comorbidities (such as seizures), a global and graduated therapeutic approach must be put in place. This treatment will be non-pharmacological as a first line, then pharmacological as a second line. A number of non-pharmacological treatment strategies for sleep disorders in typically developing children and adolescents, as well as those with ASD, have been shown to be effective. This treatment requires a combination of: 1) parental education to promote sleep development; 2) setting up bedtime rituals adapted to the child's age and particularities; 3) specific behavioral strategies including bedtime fading, gradual extinction and positive reinforcement of adapted behaviors. It is very essential that the parents are accompanied throughout this therapy. Sleep hygiene and behavioral care must also take into consideration the important role of the zeitgebers of sleep-wake rhythms, i.e. the external environmental factors involved in the synchronization of the biological clocks: regular exposure to light at adapted times, regular meal and wake-up times, social activities and times for going to school. The evidence for the effectiveness of behavioral interventions in the treatment of behavioral insomnia in the typical developmental child is strong, since 94% of children show clinically significant improvements in nighttime sleepiness and waking. By contrast, only about 25% of children with ASD are improved by an approach combining sleep hygiene and behavioral therapy. Melatonin has a special and prominent place in the drug management of sleep disorders associated with ASD. Several clinical trials have shown that melatonin is effective in treating sleep disorders in patients with ASD. This work led to the European Medicines Agency (EMA) granting marketing authorization in September 2018 for a sustained-release paediatric melatonin molecule (Slenyto®). This synthetic molecule is a prolonged release melatonin (PRM) which mimics the physiological pharmacokinetic and secretory characteristics of endogenous melatonin, having a very short blood half-life and prolonged secretion for several hours during the night. A recent study evaluated the efficacy and safety of pediatric PRM (mini-tablets) in 125 children, aged 2 to 17.5 years with mainly ASD. After 15 days on placebo, the children were randomized into two parallel groups, PRM or placebo in a double-blind design for 13 weeks. At endpoint, total sleep time was increased by an average of 57.5 minutes on PRM and only 9.14 minutes on placebo (P = 0.034). This difference between the two groups was already significant after three weeks of treatment (P = 0.006). Sleep latency was also improved in the PRM group (−39.6 minutes) compared to placebo (−12.51 minutes) (P = 0.01). Consolidated sleep duration (uninterrupted by awakenings) was improved by 77.9 minutes for the PRM group and only 25.4 minutes for the placebo group (P < 0.001). PRM was well tolerated, the most frequent side effects being headache and daytime drowsiness at the same level with PRM or placebo. In addition, the acceptability by the children for swallowing the mini-tablets was excellent (100% compliance). The efficacy and tolerability of PRM was maintained over the medium and long term in the open phase, over a total study duration of 2 years.
Les troubles du sommeil sont extrêmement fréquents (40–86 %) chez l’enfant et les adolescents, en particulier chez ceux avec un trouble du spectre de l’autisme (TSA). Ces anomalies sont, d’ailleurs, une des principales préoccupations parentales lorsque l’on a un enfant avec TSA. Les troubles du sommeil sont essentiellement des anomalies du rythme veille–sommeil – en premier lieu, des insomnies d’endormissement ou de maintien de sommeil (avec réveils nocturnes). Le traitement des troubles du sommeil est relativement systématisé : après avoir éliminé d’autres troubles spécifiques du sommeil associés à la plainte d’insomnie (comme le syndrome d’apnées du sommeil ou le syndrome de jambes sans repos), cette prise en charge sera non pharmacologique en première intention, puis pharmacologique secondairement. Les traitements non pharmacologiques des troubles du sommeil chez les enfants et les adolescents au développement normal se sont révélées très efficaces (dans 94 % des cas), mais ne sont suffisants que chez environ 25 % des personnes avec TSA. Ils nécessitent une combinaison de : 1) psychoéducation des parents pour mieux comprendre les troubles du sommeil ; 2) mise en place de rituels du coucher adaptés à l’âge et aux particularités de l’enfant ; 3) stratégies comportementales spécifiques comprenant le bedtime fading, l’extinction progressive et le renforcement positif des comportements adaptés. Sur le plan pharmacologique, la mélatonine occupe une place particulière. Plusieurs essais cliniques ont montré que la mélatonine est efficace dans le traitement des troubles du sommeil chez les patients atteints de TSA, ayant conduit l’Agence européenne des médicaments à accorder une autorisation de mise sur le marché en 2018 pour une molécule de mélatonine pédiatrique à libération prolongée (Slenyto®).
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hal-03719224 , version 1 (21-07-2022)

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Paternité - Pas d'utilisation commerciale - Pas de modification

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Citer

C. M. Schroder, M. A. Broquère, B. Claustrat, R. Delorme, P. Franco, et al.. Approches thérapeutiques des troubles du sommeil et des rythmes chez l’enfant avec TSA. L'Encéphale, 2022, 48 (3), pp.294-303. ⟨10.1016/j.encep.2021.08.005⟩. ⟨hal-03719224⟩
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