Electronically Monitored Antidepressant Adherence in Adolescents with Anxiety Disorders: A Pilot Study.

Antidepressant medication adherence patterns are inconsistent in adolescents with anxiety and related disorders, and the clinical and demographic features predicting adherence are poorly understood. In an ongoing single-site prospective trial involving adolescents (aged 12-17) with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition anxiety disorders treated with escitalopram, adherence was measured for 12 weeks using electronic monitoring caps. Adherence patterns were examined using qualitative and unsupervised clustering approaches, and predictors of adherence were evaluated using logistic regression, with demographic (age, sex, and race) and clinical variables (e.

The Impact of Development on Antidepressant and Placebo Response in Anxiety Disorders: A Bayesian Hierarchical Meta-Analytic Examination of Randomized Controlled Trials in Children, Adolescents, and Adults.

Understanding how development influences medication and placebo responses in anxiety disorders could inform treatment decisions, including age-specific first- versus second-line psychopharmacological interventions. To meta-analytically compare the trajectory of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and placebo response in youth and adults with anxiety disorders. Weekly symptom severity data were extracted from prospective, randomized, parallel-group, placebo-controlled trials of SSRIs and SNRIs in children, adolescents, and adults with anxiety disorders (generalized, separation, and social anxiety disorders as well as panic disorder).

Trajectory and magnitude of response in adults with anxiety disorders: a Bayesian hierarchical modeling meta-analysis of selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and benzodiazepines.

Background: How the trajectory of response to medication (and placebo response) varies among selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), benzodiazepines and across anxiety disorders is unknown.

Methods: We performed a meta-analysis using weekly symptom severity data from randomized, parallel-group, placebo-controlled trials of SSRIs, SNRIs, and benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in anxiety using Bayesian hierarchical models.

Gastrointestinal Symptoms in Pediatric Patients with Anxiety Disorders and Their Relationship to Selective Serotonin Reuptake Inhibitor Treatment or Placebo.

Gastrointestinal symptoms are commonly reported as adverse effects of selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacologic treatment for pediatric anxiety disorders; however, the temporal course of these symptoms during treatment, although believed to be transient, has never been prospectively evaluated. Additionally, rates of gastrointestinal symptoms and functional gastrointestinal syndromes in anxious youth are poorly understood. We examined gastrointestinal symptoms in youth with anxiety disorders during a double-blind, placebo-controlled trial of escitalopram (n = 51).

What Is the Added Benefit of Combining Cognitive Behavioral Therapy and Selective Serotonin Reuptake Inhibitors in Youth with Obsessive Compulsive Disorder? A Bayesian Hierarchical Modeling Meta-Analysis.

Treatment of obsessive-compulsive disorder (OCD) in children and adolescents frequently involves cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs), or their combination. However, how adding CBT to SSRIs affects the trajectory and magnitude of improvement has not been evaluated meta-analytically. We performed a meta-analysis using weekly data from prospective randomized parallel group trials of CBT and SSRIs in pediatric patients with OCD.

The Impact of COVID-19 Infection and Characterization of Long COVID in Adolescents With Anxiety Disorders: A Prospective Longitudinal Study.

While the coronavirus disease 2019 (COVID-19) pandemic has profoundly impacted pediatric mental health, the impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on youth with anxiety disorders has not been prospectively examined. Further, there are limited prospective data on post-acute sequelae COVID-19, including symptoms that constitute the long COVID neuropsychiatric syndrome. In December 2019, we began a longitudinal study of adolescents aged 12-17 years with DSM-5 primary anxiety disorders treated with either duloxetine or escitalopram.

Applications of the Spectral Theory of Chemical Bonding to Simple Hydrocarbons.

The finite-basis, pair formulation of the Spectral Theory of chemical bonding is briefly surveyed. Solutions of the Born-Oppenheimer polyatomic Hamiltonian that are totally antisymmetric in electron exchange are obtained from diagonalization of an aggregate matrix built up from conventional diatomic solutions to atom-localized problems. A succession of transformations of the bases of the underlying matrices and the unique character of symmetric orthogonalization in producing the archived matrices calculated "once-of-all" in the pairwise-antisymmetrized basis are described.

The impact of age on antidepressant response: A mega-analysis of individuals with major depressive disorder.

Introduction: Understanding how age affects antidepressant response in patients with major depressive disorder has been complicated by small and heterogeneous studies. Yet, understanding how age-across the lifespan-contributes to variation in response could inform treatment selection across the lifespan. This study sought to identify how age impacts antidepressant response using participant-level data from large, NIH-sponsored trials in individuals with MDD aged 12-74 years.

Adverse Effects of Antidepressant Medications and their Management in Children and Adolescents.

Introduction: Selective serotonin reuptake inhibitors (SSRIs) and, to a lesser extent, serotonin-norepinephrine reuptake inhibitors (SNRIs) are the cornerstone of pharmacotherapy for children and adolescents with anxiety and depressive disorders. These medications alleviate symptoms and restore function for many youths; however, they are associated with a distinct adverse effect profile, and their tolerability may complicate treatment or lead to discontinuation. Yet, SSRI/SNRI tolerability has received limited attention in the pediatric literature.

Initiation of Pharmacotherapy Following CBT in Anxious Youth: Results From the Child/Adolescent Anxiety Multimodal Study (CAMS).

To describe youth with anxiety disorders who initiate pharmacotherapy following cognitive-behavioral therapy (CBT) in a prospective, randomized trial and to identify predictors of the decision to use pharmacotherapy. Data from CBT-treated youth (aged 7-17 years, N = 139) in the Child/Adolescent Anxiety Multimodal Study (CAMS), a multisite, randomized controlled trial that examined the efficacy of CBT, sertraline, their combination, and placebo for pediatric anxiety disorders ( criteria), were evaluated. Initiation of pharmacotherapy following acute CBT treatment was examined over a 24-week period; the study was conducted from December 2002 through May 2007.

A Characterization of the Clinical Global Impression Scale Thresholds in the Treatment of Adolescent Depression Across Multiple Rating Scales.

The Clinical Global Impressions-Improvement (CGI-I) scale is widely used in clinical research to assess symptoms and functioning in the context of treatment. The correlates of the CGI-I with efficacy scales for adolescent major depressive disorder are poorly understood. This study focused on benchmarking CGI-I scores with changes in the Children's Depression Rating Scale-Revised (CDRS-R) and the Quick Inventory of Depressive Symptomatology-Adolescent (17-item) Self-Report (QIDS-A17-SR).

Executive Functioning in Pediatric Anxiety and Its Relationship to Selective Serotonin Reuptake Inhibitor Treatment Response: A Double-Blind, Placebo-Controlled Trial.

To characterize executive function in adolescents with generalized anxiety disorder (GAD) and its relationship to treatment. Using data from a double-blind, placebo-controlled trial of escitalopram in adolescents ( = 51) 12-17 years of age with GAD, we used the self-report version of the Behavior Rating Inventory of Executive Function (BRIEF-SR) to assess executive function, at baseline, and examined its relationship to treatment response as measured by the Pediatric Anxiety Rating Scale (PARS). For all baseline subscores of the BRIEF-SR, T-scores were significantly elevated in adolescents with GAD compared to an age- and sex-matched normative healthy sample.

Socioeconomic Predictors of Treatment Outcomes Among Adults With Major Depressive Disorder.

Objective: In this study, the authors sought to examine the impact of socioeconomic variables on outcomes of pharmacotherapy treatments for major depressive disorder in analyses that controlled for treatment access and level of care.

Methods: The authors used data from the Combining Medications to Enhance Depression Outcomes study, a prospective clinical trial conducted from March 2008 to April 2014 with 665 adults who had major depressive disorder and were randomly assigned to three pharmacotherapeutic treatments, to develop Bayesian hierarchical models of treatment trajectories for change in Quick Inventory of Depressive Symptomatology-Self-Report ratings. Posterior tail probabilities were used to evaluate the effects of education, income, race-ethnicity, and employment on treatment outcomes.

Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized Trial.

Current pharmacologic treatments for pediatric anxiety disorders (e.g., selective serotonin reuptake inhibitors (SSRIs)) frequently use "one size fits all" dosing strategies based on average responses in clinical trials.

Combining selective serotonin reuptake inhibitors and cognitive behavioral therapy in youth with depression and anxiety.

Background: Treatment studies of children and adolescents with internalizing disorders suggest that the combination of a selective serotonin reuptake inhibitor (SSRI) and cognitive behavioral therapy (CBT) consistently produces greater improvement than either treatment alone. We sought to determine how response to combined treatment varies across disorders (anxiety versus depression), and by specific patient characteristics.

Methods: Three large National Institutes of Health-funded trials of children and adolescents with major depression (n = 2) and anxiety disorders (n = 1) were evaluated, each comparing CBT + SSRI to SSRI only, Bayesian Hierarchical Models (BHMs) were used, for endpoint response, time course of response and predictors of response in participants who received SSRI or SSRI+CBT.

Pharmacologic predictors of benzodiazepine response trajectory in anxiety disorders: a Bayesian hierarchical modeling meta-analysis.

Background: Despite frequent benzodiazepine use in anxiety disorders, the trajectory and magnitude of benzodiazepine response and the effects of benzodiazepine potency, lipophilicity, and dose on improvement are unknown.

Methods: We performed a meta-analysis using weekly symptom severity data from randomized, parallel group, placebo-controlled trials of benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model.

Acute neurofunctional effects of escitalopram during emotional processing in pediatric anxiety: a double-blind, placebo-controlled trial.

Anxiety disorders are the most common mental disorders in adolescents. However, only 50% of pediatric patients with anxiety disorders respond to the first-line pharmacologic treatments-selective serotonin reuptake inhibitors (SSRIs). Thus, identifying the neurofunctional targets of SSRIs and finding pretreatment or early-treatment neurofunctional markers of SSRI treatment response in this population is clinically important.

The Impact of Failed Antidepressant Trials on Outcomes in Children and Adolescents with Anxiety and Depression: A Systematic Review and Meta-Analysis.

To identify predictors of medication-placebo differences in double-blind placebo-controlled antidepressant trials in children and adolescents with anxiety and depression. Clinical trials in patients <18 years of age with major depressive disorder or generalized, separation or social anxiety disorders were obtained from PubMed, the Cochrane Database and clinicaltrials.gov searches from inception through 2019.

Acute Neurofunctional Effects of Escitalopram in Pediatric Anxiety: A Double-Blind, Placebo-Controlled Trial.

Objective: Amygdala-ventrolateral prefrontal cortex (VLPFC) circuitry is disrupted in pediatric anxiety disorders, yet how selective serotonin reuptake inhibitors (SSRIs) affect this circuitry is unknown. We examined the impact of the SSRI escitalopram on functional connectivity (FC) within this circuit, and whether early FC changes predicted treatment response in adolescents with generalized anxiety disorder (GAD).

Method: Resting-state functional magnetic resonance (MR) images were acquired before and after 2 weeks of treatment in 41 adolescents with GAD (12-17 years of age) who received double-blind escitalopram or placebo for 8 weeks.

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.

Greater Dynamic and Lower Static Functional Brain Connectivity Prospectively Predict Placebo Response in Pediatric Generalized Anxiety Disorder.

Placebo response is one of the most significant barriers to detecting treatment effects in pediatric (and adult) clinical trials focusing on affective and anxiety disorders. We sought to identify neurofunctional predictors of placebo response in adolescents with generalized anxiety disorder (GAD) by examining dynamic and static functional brain connectivity. Before randomization to blinded placebo, adolescents, aged 12-17 years, with GAD ( = 25) underwent resting state functional magnetic resonance imaging.