l-Dopa improves Restless Legs Syndrome and periodic limb movements in sleep but not Attention-Deficit-Hyperactivity Disorder in a double-blind trial in children

Abstract

Background In a previous open-label study, dopaminergic agents improved Restless Legs Syndrome (RLS) and Periodic Limb Movements in Sleep (PLMS), as well as Attention-Deficit-Hyperactivity Disorder (ADHD) in children with both disorders. We therefore conducted a double-blind placebo-controlled trial of L-DOPA in ADHD children with and without RLS/PLMS. Methods Two groups of patients (total n=29), those with ADHD only or those with ADHD and RLS/PLMS were randomized to L-DOPA or placebo therapy. At baseline and after therapy patients were assessed with Conners' Parent and Teacher Rating Scales; polysomnography; RLS rating scale; and neuropsychometric measures of memory, learning, attention, and vigilance. Results L-DOPA improved RLS/PLMS symptoms in all patients with those disorders compared with placebo (p = .007). When assessed by the Conners' Scales before therapy, ADHD was more severe in children without RLS/PLMS than in children with RLS/PLMS (p=0.006). L-DOPA had no effect on Conners' scales, sleep, or neuropsychometric tests when all patients treated with drug were compared to those on placebo or when patients with ADHD only were compared to those with ADHD and RLS/PLMS. Conclusions In this first double-blind study of a dopaminergic therapy in children with RLS/PLMS, L-Dopa significantly improved RLS/PLMS but not ADHD. These results, however, should be interpreted carefully since they may have been influenced by the relatively small sample size and the baseline differences in severity of ADHD symptoms. Further work needs to be done to elucidate the relationship between dopamine, ADHD and RLS/PLMS.

Time structure of leg movement activity during sleep in attention-deficit/hyperactivity disorder and effects of levodopa

“…More detailed information on excluded patients and those who dropped out can be found in the above mentioned report [30].…”

“…As part of a multisite study investigating the effects L-DOPA on in children with ADHD, baseline end point PSG was performed; the results of the study have been reported earlier [30,31]. In our paper, we have reanalyzed data from a subsample of children aged seven to 12 years recruited at the Carle Foundation Hospital/University of Illinois.…”

Headache and ADHD in Pediatric Age: Possible Physiopathological Links

“…PLM has also been associated to both headache and ADHD. A dopaminergic dysfunction and iron deficiency (ID) may be the neuroanatomical substrate linking migraine, ADHD, and PLM [64]. Iron is a coenzyme necessary for the synthesis and catabolism of monoaminergic neurotransmitters, which are implicated in ADHD pathophysiology [65]; ID is associated with decreased dopamine transporter expression [66]; variation in the corresponding dopamine transporter gene has been linked to genetic vulnerability for ADHD [67], and finally, ID may lead to dysfunction in the basal ganglia [68], which have been implicated in the pathophysiology of ADHD [69].…”

To Sleep or Not To Sleep: A Systematic Review of the Literature of Pharmacological Treatments of Insomnia in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

“…A relationship has been found between RLS and ADHD, and it is posited that RLS may exacerbate or delay the onset of ADHD symptoms, and may also result in a higher incidence of bedtime resistance (Cortese et al 2005). Because of this relationship, it is assumed that there is a shared dopaminergic system dysfunction in both sleep disorders and ADHD (Silvestri et al 2009); however, it has been found that l-DOPA does improve RLS but not ADHD (England et al 2011), indicating that the relationship between RLS and ADHD may not be the result of a dopaminergic dysfunction.…”