Factors Related to Placebo Response in Randomized, Double-Blind Clinical Trials of Antidepressants in Children and Adolescents: A Meta-regression Analysis.

BACKGROUND AND OBJECTIVE: Many randomized clinical trials (RCTs) for antidepressants in children and adolescents have failed to demonstrate efficacy due to a high placebo response. The aim of this study was to identify the potential factors affecting placebo response using meta-regression analysis of RCTs for antidepressants in children and adolescents using the Children's Depressive Rating Scale-Revised (CDRS-R) as the outcome. METHODS: PubMed and ClinicalTrials.gov were searched for randomized, double-blind, placebo-controlled trials of antidepressants for the acute treatment of major depressive disorder in children and adolescents. The outcome used in the present study was the mean change of the CDRS-R total score from baseline to the last assessment for the primary efficacy in the placebo arm. Potential factors related to the placebo response, such as study design, operational, and patient factors, were explored using meta-regression. RESULTS: The analyses included 23 trials. On multivariable meta-regression, setting up a placebo lead-in period was significantly associated with a smaller placebo response in the CDRS-R. CONCLUSION: Setting up a placebo lead-in period should be considered in future clinical trials of antidepressants in adolescents and children.

Difficulties of diagnosing idiopathic hypertrophic pachymeningitis in children: Case report and literature review.

Hypertrophic pachymeningitis (HP) is a rare inflammatory disorder characterised by local or diffuse thickening of the cranial and spinal dura mater. HP occurs owing to idiopathic or secondary causes, including autoimmune disease, infection, and trauma. HP has mainly been reported in adults, with few reported cases in children. We encountered an 11-year-old boy with idiopathic HP who presented with chronic inflammation and daily occipital headache. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) helped us to diagnose him with HP. He was successfully treated with corticosteroids and azathioprine with no recurrence. We also conducted a literature review of childhood-onset HP and found only 16 cases, including our patient. Seven patients had idiopathic HP, and the remaining nine had secondary HP, including two with rheumatic disease. The most common clinical symptoms were headache (68.8%) and cranial nerve-related symptoms (68.8%). Inflammatory laboratory markers were elevated in 60% of patients with available data. Fifteen cases were diagnosed using Gd-enhanced MRI. The main initial treatment was steroids and/or immunosuppressants, to which 87.5% of patients responded. However, two patients with HP associated with trauma and neuroblastoma (12.5%) died, and seven patients (43.8%) had left cranial nerve-related sequelae. As the prognosis for childhood HP is poor, early diagnosis and treatment are essential. Children with headache, cranial nerve symptoms, and elevated inflammatory marker levels should be suspected of having HP and Gd-enhanced MRI should be considered.