Use of clonidine in children with autism spectrum disorders

Abstract

Children with autism spectrum disorders (ASD) often exhibit sleep and behavioral disorders. Treatment of sleep disorders can be difficult in these children. Clonidine, an α2-adrenergic receptor agonist, has been shown to be effective in reducing impulsivity, inattention, and hyperactivity, as well as in serving as a sedative for medial procedures. An open labeled retrospective study of clonidine in treatment of insomnia, and/or hyperactivity, inattention, mood disorder, and aggressive behaviors was conducted using parent reports of sleep initiation and maintenance, as well as behaviors prior and during clonidine treatment. Clonidine was effective in reducing sleep initiation latency and night awakening, to a less degree in improving attention deficits hyperactivity, mood instability and aggressiveness in this cohort of 19 children with ASD. The side effects were largely tolerable. Further evaluation with placebo-controlled double-blind clinical trial of clonidine use in ASD will provide more insight into the clinical efficacy and safety of the medicine in ASD.

Introduction

Children with autism spectrum disorders (ASD) suffer from medical and psychiatric conditions including sleep disturbances, gastrointestinal dysfunction, mood disorders, aggressive behaviors, and attention-deficit hyperactivity [1], [2], [3], [4], [5]. With respect to the sleep disturbances, it has been reported that between 40% and 80% of children with ASD have problematic sleep patterns that are often severe in nature [6], [7], [8], [9]. The sleep problems include difficulty in settling to sleep, lengthy episodes of night waking with or without confusion, early morning awakening, shortened night sleep, parasomnia (including bruxism), and irregularities of the sleep/wake rhythm [1], [10], [11], [12], [13], [14], [15], [16], [17]. The impact of these sleep disorders in children with ASD is of particular concern in light of the increased burden and stress experienced in parenting a child with ASD. Sleep problems have been correlated with family or parental distress in normally developing children and in children with an intellectual disability[18], [19]. The children with ASD who had sleep disorders were frequently reported to have more problems in social relatedness, and other daytime behavior difficulties [20]. Parents reported improvement of daytime performance following treatment of the sleep disorders [21], [22], [23].

In addition to the sleep disturbances, other behavioral disorders occur with higher frequency in children with ASD and present still additional problems for their caregivers. These include mood disorders, aggressiveness and self-injurious behaviors, obsessive- and compulsive-like behaviors, anxiety, and ritualistic behaviors [3], [5], [24]. Unfortunately, treatment of these medical and behavioral symptoms associated with ASD has been challenging. Pakyurek et al. [21] reported behavioral and sleep improvement in two children after tonsillar and adenoidectomy. However, for most children with ASD whose causes of sleep disorder or behavioral disorders remain unidentified, treatment is largely symptom-based. Melatonin has been shown to be efficacious in some ASD children for treatment of sleep onset insomnia. Unfortunately, the beneficial effects of melatonin diminish over time despite administration of increasing doses [25]. Traditional hypnotics and sedatives exhibit various degrees of beneficial effects but present the risk of side effects such as sedation during daytime. The other behavioral disorders associated with ASD could be quite refractory to medication. Atypical neuroleptics, SSRIs, anti-depressants, anti-convulsants, and other agents have all been tried in targeting various behavioral symptoms with variable degree of success, even when used in conjunction with behavioral therapy [26]. Thus, there is a need to identify a safe and efficacious treatment for the broad spectrum of medical and behavioral symptoms associated with ASD.

Clonidine is a centrally acting α2-adrenergic agonist that has been administered to children with ASD for the treatment of hyperactivity and impulsivity, sleep disorder as well as for sedation, prior to EEG recording [27], [28], [29], [30]. A placebo-controlled, double-blind trial of transdermal clonidine showed it to be effective in reducing hyperarousal in children with ASD and that this calming action resulted in improved social relationships, improved affectual responses, and an overall improvement in Clinical Global Impression scales in some subjects [27]. However, Hazell [29] believed clonidine along with dexamphetamine, clomipramine, mirtazapine, and fluoxetine are of unlikely benefit in treating attention deficits and hyperactivity disorder (ADHD) in children with autism. Our own anecdotal observations indicated that clonidine administration may be beneficial for the treatment of sleep disorders in children with or without ASD.

This study is an open-labeled, semi-quantitative pilot study using parental report to examine the efficacy of clonidine in the treatment of sleep and behavioral disorders in children with ASD.