Nationwide Japanese Database Study Maps Care Patterns in Pediatric Orthostatic Dysregulation

A nationwide analysis of more than 7,000 children and adolescents newly diagnosed with orthostatic dysregulation in Japan has revealed, for the first time at this scale, how the condition presents and is managed in everyday clinical practice. The findings paint a picture of a heterogeneous patient population in which mental health and behavioral disorders are the most common comorbidity category, and in which fewer than half of patients receive medication at diagnosis.

Orthostatic dysregulation is a condition characterized by an inability to tolerate an upright posture due to autonomic nervous system imbalance. Patients typically present with symptoms such as syncope, dizziness, and fatigue that can impair quality of life. In Japan, the condition is estimated to affect roughly 5 percent of elementary school students and 10 percent of junior and senior high school students, and it is considered a leading contributor to prolonged school non-attendance, accounting for an estimated 30 to 40 percent of such cases. While internationally similar presentations are often classified as orthostatic intolerance or postural orthostatic tachycardia syndrome, in Japan orthostatic dysregulation is recognized as a physical disorder but has historically been managed within a psychosomatic framework.

The new study addressed a persistent evidence gap. Previous Japanese research on the condition had largely been restricted to single-center reports or surveys conducted at specialized psychosomatic medicine institutions, which tend to handle severe or complex cases and may not reflect the broader patient population.

The demographic profile of the cohort reflected the condition’s known predilection for adolescents. The median age at diagnosis was 13 years, with an interquartile range of 12 to 14, and 55.6 percent of the patients were female. The annual number of incident diagnoses generally increased over the study period, with a transient decline in 2020 followed by a recovery in 2021 and 2022. The mean annual count did not differ significantly between the pre-COVID-19 period of 2016 to 2019 and the post-COVID-19 period of 2020 to 2022, according to a Wilcoxon rank-sum test that yielded a P value of 0.23. The authors note that although pediatric psychosomatic conditions including orthostatic dysregulation have been reported to increase following the pandemic, their data did not show a significant difference between the two periods, and the 2020 dip may reflect reduced healthcare access during the early phase of the pandemic.

Comorbidity analysis, based on diagnoses recorded from one year before to three months after the initial orthostatic dysregulation diagnosis, showed that mental health and behavioral disorders were the most common category at 23.6 percent, followed by gastroenterological disorders at 17.6 percent and metabolic or endocrine disorders at 17.4 percent. Among specific conditions, sleep disorders were the most prevalent at 10.2 percent, followed by school non-attendance at 9.3 percent and autism spectrum disorder or attention-deficit hyperactivity disorder at 7.1 percent, with depression recorded in 2.7 percent of patients. Notably, these overall prevalence figures were lower than those reported in earlier single-center studies. The authors attribute this difference to variations in study population: unlike specialized psychosomatic institutions that manage severe or complex cases, their cohort represents the general orthostatic dysregulation population across secondary and tertiary care, where comorbidities appear less prevalent than previously assumed.

Pharmacotherapy emerged as a minority approach at the initial stage of care. Overall, 44.0 percent of patients received at least one prescription in the month of or the month following diagnosis, with a mean of 1.3 medications per treated patient. Among the treated subgroup, 83.6 percent received medications commonly used for orthostatic dysregulation. Midodrine dominated the prescribing landscape at 78.3 percent of treated patients, followed by amezinium metilsulfate at 6.7 percent and propranolol at 2.8 percent, a hierarchy consistent with previous reports identifying midodrine as first-line pharmacotherapy. Sleep medications, specifically ramelteon and melatonin, were prescribed to 9.4 percent of treated patients, with ramelteon accounting for 7.5 percent and melatonin for 1.9 percent. Various Japanese herbal medicines, known as Kampo, were also prescribed. Of the treated subgroup, 74.7 percent were managed with a single medication, indicating that polypharmacy is uncommon at the initial phase of treatment. The authors interpret the fact that more than half of patients received no pharmacotherapy at diagnosis as reflecting adherence to Japanese guidelines that prioritize non-pharmacological care.

Subgroup analyses stratified by prescription pattern uncovered clinically meaningful differences within the population. Patients receiving any prescription showed higher prevalence of systemic comorbidity categories, including metabolic or endocrine, neurological, respiratory, hematological or immunological, and gastroenterological disorders, as well as specific conditions such as sleep disorder, irritable bowel syndrome, asthma, and iron-deficiency anemia. Most strikingly, the subgroup prescribed sleep medications showed a significantly higher prevalence of mental health and behavioral disorders and frequently presented with school non-attendance, depression, sleep disorder, and autism spectrum disorder or attention-deficit hyperactivity disorder. Patients not prescribed common orthostatic dysregulation medications were significantly more likely to receive sleep medications and specific Kampo medicines, each with P values below 0.001, while those prescribed sleep medications were significantly less likely to receive the common orthostatic dysregulation drugs. The authors suggest that patients requiring sleep medications likely represent a clinically distinct subgroup with more complex neurodevelopmental and psychiatric backgrounds, for whom treatment focused solely on orthostatic dysregulation symptoms may be insufficient.

Medical resource utilization was substantial in the diagnostic phase. The most frequently performed practices within the observation window were blood tests at 48.6 percent of patients, diagnostic imaging at 35.9 percent, and electrocardiograms at 24.2 percent. Laboratory data were available for 49.1 percent of patients overall, and physiological tests were performed for 29.3 percent. The authors interpret this pattern as evidence that clinicians actively screen for organic diseases to rule out other causes of the patients’ symptoms, a practice aligned with clinical guideline recommendations. The subgroup receiving any prescription generally underwent medical practices at higher rates, whereas the subgroup prescribed sleep medications generally underwent fewer procedures, with two exceptions: specialized psychiatric therapy, which was 14.9 percentage points more common in that subgroup with a 95 percent confidence interval of 10.2 to 19.6, and medical guidance and management fees, which were 9.1 percentage points more common with a confidence interval of 4.6 to 13.6, both with P values below 0.001.

The study’s limitations warrant careful interpretation. The Medical Information Analysis databank covers mainly secondary and tertiary care institutions, so the study population may be more complex than patients seen in primary care, potentially overestimating comorbidity prevalence and resource utilization. Facility-level information such as regional classification and hospital size was unavailable, precluding analysis of geographic or institutional variation. Reliance on administrative claims data may have contributed to lower recorded comorbidity rates, since clinicians may prioritize coding the primary diagnosis for reimbursement while under-reporting co-existing psychiatric or neurodevelopmental conditions. The observation window extended only three months after diagnosis, so conditions identified later, particularly psychiatric or neurodevelopmental diagnoses, may be underestimated. Finally, because orthostatic dysregulation is a clinical entity primarily recognized in Japan and lacks a specific ICD-10 code, some misclassification cannot be excluded, though the two-step identification approach was designed to reduce this risk.

Nevertheless, the authors argue that the nationwide coverage of the database compensates for the limited availability of procedures and laboratory tests in primary care and positions the study to bridge the evidence gap between general pediatric settings and specialized psychosomatic institutions. Their conclusion emphasizes the clinical heterogeneity of orthostatic dysregulation and highlights the need for tailored therapeutic strategies, including attention to sleep and mental health in the subgroup of patients with complex comorbidity profiles, to support more effective care across Japan’s pediatric healthcare system.

Subject of Research: Clinical characteristics, comorbidities, and healthcare utilization among pediatric patients with orthostatic dysregulation in Japan

Article Title: Clinical characteristics and healthcare utilization of orthostatic dysregulation in Japan: a nationwide descriptive study

Article References: Shinno, K., Iijima, H., Ishitsuka, K., Inoue, N., Hashimoto, Y., Nagai, A., Kamimaki, I., & Nagamitsu, S. (2026). Clinical characteristics and healthcare utilization of orthostatic dysregulation in Japan: a nationwide descriptive study. BioPsychoSocial Medicine, 20(1), Article 16. https://doi.org/10.1186/s13030-026-00363-1

Image Credits: AI Generated

DOI: 10.1186/s13030-026-00363-1

Keywords: orthostatic dysregulation, pediatrics, Japan, nationwide database study, autonomic nervous system, comorbidities, midodrine, sleep disorders, school non-attendance, healthcare utilization, psychosomatic medicine, administrative claims data