Very-Low-Dose Levodopa Therapy for Pediatric Neurological Disorders: A Preliminary Questionnaire in Japan.

Introduction: Post-synaptic dopamine receptor supersensitivity (DARSS) has been extensively researched by Dr. Masaya Segawa, who has investigated the efficacy of very-low-dose levodopa therapy (VLDT; 0.5-1 mg/kg/day). Considerable Japanese research supports the possibility that VLDT could be used to treat pediatric neurological disorders. We conducted an on-line survey in 2014 to collect real-world data on the use of VLDT to treat DARSS. Methods: A two-step survey, including a screening test and questionnaire, was posted on a private internet site that could be accessed via the VLDT Research Group home page, and 1,165 pediatric neurologists across Japan were invited to complete it. Results: A total of 25 respondents reported prescribing VLDT; 19 used VLDT to treat autism spectrum disorder, 14 for tics, 12 for speech delay, 9 for Rett syndrome, 7 for attention-deficit/hyperactivity disorder, intellectual disability, and 6 for sleep problems. Twelve respondents reported prescribing a dose of 0.5 mg/kg. Twenty-two reported that VLDT was effective for treating behavioral problems, and twenty reported a good efficacy for treating motor symptoms. Adverse events had a low incidence. Notably, respondents chose VLDT for its possible action in DARSS and for its safety. VLDT was commonly used for behavioral problems in patients younger than 5 years, and for motor symptoms in aged 5-9 years. Conclusion: VLDT could safely treat behavioral and motor symptoms in pediatric neurological disorders. In contrast, dopamine antagonists are associated with potent efficacy, but with adverse effects such as sleepiness and obesity. Further surveys should be conducted with a broader participants.

[A nationwide survey on the uses of melatonin and ramelteon in Japanese children].

OBJECTIVE: We carried out a questionnaire survey to investigate the uses of melatonin and ramelteon in Japanese children. METHODS: We sent a questionnaire to councilors of the Japanese Society of Child Neurology by e-mail, and sent the same questionnaire to members of the Japanese Society of Pediatric Psychiatry and Neurology by postal mail. RESULTS: During the first phase of the survey, 220 responses were obtained, and 45% of the respondents prescribed melatonin. Imported supplements and chemical reagents were used by 64% and 29% of melatonin prescribers, respectively. Some prescribed melatonin without patient consent or institutional approval. In patients with pervasive developmental disorder, cerebral palsy, attention-deficit hyperactivity disorder, Rett syndrome, and visual disturbance, melatonin was prescribed by 37%, 29%, 10%, 6%, and 6% of the respondents, respectively. In terms of sleep disorders, melatonin was prescribed by 49% and 42% of respondents in patients with circadian rhythm disorders and insomnia, respectively. Ramelteon was prescribed by 52% of respondents. Regarding types of target diseases and sleep disorders, the use of ramelteon differed little from that of melatonin. In the second phase of the survey on the use of melatonin, 23 doctors prescribed the drug for 254 patients. The daily effective dose ranged from 0.2 mg to 8 mg in patients aged 2 months to 37 years. In more than 60% of the patients who took melatonin, PDD was diagnosed. In the patients with melatonin for insomnia, 90% and 25% had difficulty falling asleep and disorders in circadian rhythm, respectively. CONCLUSIONS: Both melatonin and ramelteon were widely prescribedin Japanese children. Melatonin tended to be used without sufficient ethical consideration in Japan, indicating the necessity of melatonin as medicine. Then, careful determination of an applicable dose are required in future studies.

[Drug therapy for AD/HD investigation of usefulness of extended-release methylphenidate and atomoxetine from the viewpoint of persistency rate].

OBJECTIVE: Currently, extended-release methylphenidate (MPH) and atomoxetine (ATX) are used for the medical treatment of AD/HD. The purpose of this study is to investigate the current state of these treatments from the viewpoint of the persistency rate of each drug. METHODS: Of patients who had AD/HD or pervasive developmental disorder (PDD) associated with the symptoms of AD/HD, 460 cases who receiving MPH and 121 receiving ATX were investigated in terms of the diagnosis, the persistency rate, the persistency rate by the diagnostic name, reasons for discontinuation, and concomitant drugs as continual medications. RESULTS: The cases who continued MPH accounted for 59.8% (275/460), and those who continued ATX accounted for 49.6% (60/121). There were 40 cases who received MPH and ATX concomitantly. The persistency rate of ATX among those who had PDD was low. CONCLUSIONS: The persistency rate of ATX was low because it was used for serious cases and MPH included the cases with proven effectiveness and discontinuation. There were also many cases requiring combination therapy. MPH had a high persistency rate for PDD, which did not necessarily mean that it was generally effective.

[Care continuity for patients with attention deficit hyperactivity disorder (ADHD) during transition from childhood to adulthood].

It is necessary to understand a basic condition of ADHD and then, to aim at the improvement of communications skills, to guide that it is possible to orient oneself to the community, and to bring up confidence and self-esteem as well as the puerility since adolescence. When the relief of symptoms is strongly hoped because the core symptom remains or there are a concomitant trouble and coexisting illness even if young person or adult, the central nerve stimulus is also necessary as well as the puerility.

[Clinical assessment of the effect of switch from immediate-release to extended-release methylphenidate in 181 patients with isolated attention deficit/hyperactivity disorder (AD/HD) or AD/HD associated with pervasive developmental disorder].

We switched medication from conventional immediate-release preparations of methylphenidate to extended-release tablets (an osmotic release oral system) in 165 of 181 cases with attention deficit/hyperactivity disorder (AD/HD), in accordance with the revised indications for these tablets. We investigated the types of developmental disorders, doses of the drug, efficacy, adverse effects, concomitant medication, other relevant problems, and so on, prior to switching the medications. The most common types of developmental disorders were AD/HD with symptoms of pervasive developmental disorder (PDD) and PDD with symptoms of AD/HD. The efficacy evaluation revealed that the extended release tablets had efficacy equivalent to or greater than that of the immediate release preparation. The efficacy rate was 82.7% in our patients. However, cases with difficulty ingesting the tablets, requiring small doses, and those over 18 years of age still seen in the pediatrics department, remained as problematic issues which require further consideration.