Antidepressant Treatment Duration in Pediatric Depressive and Anxiety Disorders: How Long is Long Enough?

Anxiety and depressive disorders are common in the pediatric primary care setting, and respond to both psychotherapeutic and psychopharmacologic treatment. However, there are limited data regarding the optimal treatment duration. This article systematically reviews guidelines and clinical trial data related to antidepressant treatment duration in pediatric patients with depressive and anxiety disorders. The extant literature suggests 9-12 months of antidepressant treatment for youth with major depressive disorder. For generalized, separation and social anxiety disorders, 6-9 months of antidepressant treatment may be sufficient, though many clinicians extend treatment to 12 months based on extrapolation of data from adults with anxiety disorders. Such extended treatment periods may decrease the risk of long-term morbidity and recurrence; however, the goal of treatment is ultimately remission, rather than duration of antidepressant pharmacotherapy. Moreover, while evidence-based guidelines represent a starting point, appropriate treatment duration varies and patient-specific response, psychological factors, and timing of discontinuation must be considered for individual pediatric patients

Neuroendocrine aspects of pediatric aggression: Can hormone measures be clinically useful?

Pediatric aggression is common in human societies, mainly presenting as impulsive aggression or predatory aggression. Numerous psychiatric disorders can contain aggression as a symptom, leading to difficulties in diagnosis and treatment. This review focuses on the biological systems that affect pediatric aggression. We review the hypothalamic–pituitary–adrenal (HPA) axis, the hypothalamic–pituitary–gonadal (HPG) axis, and the mechanisms by which these axes influence the body and mind of aggressive children and adolescents. Although this review focuses on the HPA and HPG axes, it is important to note that other biological systems have relationships with these two axes. Based on the results of the studies reviewed, elevated cortisol concentrations were associated with impulsive aggression, whereas, low levels of cortisol were associated with callous-unemotional traits similar to predatory aggression. Higher levels of dehydroepiandrosterone were correlated with higher levels of aggression as were higher levels of testosterone. However, there have been discrepancies in the results between various studies, indicating the need for more research on hormonal levels and pediatric aggression. In the future, hormonal levels may be useful in determining what treatments will work best for certain pediatric patients

Elevated Salivary Alpha Amylase in Adolescent Sexual Abuse Survivors with Posttraumatic Stress Disorder Symptoms

Objective: Little is known regarding neuroendocrine responses in adolescent girls with posttraumatic stress disorder (PTSD) who have experienced sexual abuse. Therefore, we collected saliva samples three times daily for 3 days to assess concentrations of salivary alpha amylase (sAA) – a surrogate marker for autonomic nervous system (ANS) activity and, in particular, sympathetic activity – in sexually abused adolescent girls

Influence of CYP2C19 Metabolizer Status on Escitalopram/Citalopram Tolerability and Response in Youth With Anxiety and Depressive Disorders

In pediatric patients, the selective serotonin reuptake inhibitors (SSRIs) escitalopram and citalopram (es/citalopram) are commonly prescribed for anxiety and depressive disorders. However, pharmacogenetic studies examining CYP2C19 metabolizer status and es/citalopram treatment outcomes have largely focused on adults. We report a retrospective study of electronic medical record data from 263 youth < 19 years of age with anxiety and/or depressive disorders prescribed escitalopram or citalopram who underwent routine clinical CYP2C19 genotyping. Slower CYP2C19 metabolizers experienced more untoward effects than faster metabolizers (p = 0.015), including activation symptoms (p = 0.029) and had more rapid weight gain (p = 0.018). A larger proportion of slower metabolizers discontinued treatment with es/citalopram than normal metabolizers (p = 0.007). Meanwhile, faster metabolizers responded more quickly to es/citalopram (p = 0.005) and trended toward less time spent in subsequent hospitalizations (p = 0.06). These results highlight a disparity in treatment outcomes with es/citalopram treatment in youth with anxiety and/or depressive disorders when standardized dosing strategies were used without consideration of CYP2C19 metabolizer status. Larger, prospective trials are warranted to assess whether tailored dosing of es/citalopram based on CYP2C19 metabolizer status improves treatment outcomes in this patient population

Escitalopram in Adolescents with Generalized Anxiety Disorder: A Double-Blind, Randomized, Placebo-Controlled Study

Background: Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat pediatric anxiety disorders, including generalized anxiety disorder (GAD); however, their efficacy and tolerability are difficult to predict. This study evaluated the efficacy and tolerability of escitalopram in adolescents with GAD (DSM-IV-TR) and the impact of variants in HTR2A and serotonin transporter (SLC6A4) genes and cytochrome P450 2C19 (CYP2C19) phenotypes on response as well as CYP2C19 phenotype on escitalopram pharmacokinetics from February 2015 through November 2018. Methods: Patients were treated with escitalopram (forced titration to 15 mg/d, then flexible titration to 20 mg/d) (n = 26, mean ± SD age: 14.8 ± 1.7 years) or placebo (n = 25, mean ± SD age: 14.9 ± 1.6 years) for 8 weeks. Outcomes were the change in scores on the Pediatric Anxiety Rating Scale (PARS) and Clinical Global Impressions (CGI) scales as well as vital signs and adverse events. Plasma escitalopram and desmethylcitalopram area under the curve during 24 hours (AUC0-24) and maximum concentration (Cmax) were determined and compared across CYP2C19 phenotypes. Results: Escitalopram was superior to placebo for mean ± SD baseline-to-endpoint change in PARS (-8.65 ± 1.3 vs -3.52 ± 1.1, P = .005) and CGI scores, and increasing CYP2C19 metabolism was associated with decreases in escitalopram Cmax (P = .07) and AUC0-24 (P < .05). Vital signs, corrected QT interval, and adverse events were similar in patients who received escitalopram and placebo. Conclusions: Escitalopram reduces anxiety symptoms, and pharmacogenetics variables influence the trajectory and magnitude of improvement. Variation in CYP2C19 metabolism accounts for significant differences in escitalopram pharmacokinetics, raising the possibility that CYP2C19 phenotype should be considered when prescribing escitalopram

The FAIR Guiding Principles for scientific data management and stewardship

There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders—representing academia, industry, funding agencies, and scholarly publishers—have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community

ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Altres ajuts: Anxiety Disorders Research Network European College of Neuropsychopharmacology; Claude Leon Postdoctoral Fellowship; Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 44541416-TRR58); EU7th Frame Work Marie Curie Actions International Staff Exchange Scheme grant 'European and South African Research Network in Anxiety Disorders' (EUSARNAD); Geestkracht programme of the Netherlands Organization for Health Research and Development (ZonMw, 10-000-1002); Intramural Research Training Award (IRTA) program within the National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, MH002781); National Institute of Mental Health under the Intramural Research Program (NIMH-IRP, ZIA-MH-002782); SA Medical Research Council; U.S. National Institutes of Health grants (P01 AG026572, P01 AG055367, P41 EB015922, R01 AG060610, R56 AG058854, RF1 AG051710, U54 EB020403).Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders

Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the enigma-anxiety working group

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology