Treatment Of Anxiety In Children Research Articles

Paradigms and Practice Shifts: A Topical Narrative Review of the Evolving Face of Exposure-Based Treatment for Youth

Abstract: Exposure therapy is the gold standard treatment for anxiety and obsessivecompulsive disorders in children, adolescents, and adults. Inhibitory Learning Theory offers a nuanced and advanced perspective on exposure treatment positing that violating threat expectancies is more important than habituation. This paper highlights the effectiveness of inhibitory learning theory-guided exposure procedures for youth with anxiety and OCD, chronic pain, and eating disorders. A topical review focusing on the theoretical foundations of inhibitory learning theory, crucial augmentations of the approach, and outcomes with pediatric patients diagnosed with anxiety, eating, and pain disorders is presented. The literature review indicated that inhibitory learning theory-driven exposure produced beneficent outcomes in the identified populations. Various limitations and future directions were discussed. Limitations notwithstanding, inhibitory learning theory-led exposure represents a viable treatment option for pediatric patients with anxiety, eating, and chronic pain disorders.

Machine Learning-Based Prediction of Escitalopram and Sertraline Side Effects With Pharmacokinetic Data in Children and Adolescents.

Selective serotonin reuptake inhibitors (SSRI) are the first-line pharmacologic treatment for anxiety and depressive disorders in children and adolescents. Many patients experience side effects that are difficult to predict, are associated with significant morbidity, and can lead to treatment discontinuation. Variation in SSRI pharmacokinetics could explain differences in treatment outcomes, but this is often overlooked as a contributing factor to SSRI tolerability. This study evaluated data from 288 escitalopram-treated and 255 sertraline-treated patients ≤ 18 years old to develop machine learning models to predict side effects using electronic health record data and Bayesian estimated pharmacokinetic parameters. Trained on a combined cohort of escitalopram- and sertraline-treated patients, a penalized logistic regression model achieved an area under the receiver operating characteristic curve (AUROC) of 0.77 (95% confidence interval (CI): 0.66-0.88), with 0.69 sensitivity (95% CI: 0.54-0.86), and 0.82 specificity (95% CI: 0.72-0.87). Medication exposure, clearance, and time since the last dose increase were among the top features. Individual escitalopram and sertraline models yielded an AUROC of 0.73 (95% CI: 0.65-0.81) and 0.64 (95% CI: 0.55-0.73), respectively. Post hoc analysis showed sertraline-treated patients with activation side effects had slower clearance (P = 0.01), which attenuated after accounting for age (P = 0.055). These findings raise the possibility that a machine learning approach leveraging pharmacokinetic data can predict escitalopram- and sertraline-related side effects. Clinicians may consider differences in medication pharmacokinetics, especially during dose titration and as opposed to relying on dose, when managing side effects. With further validation, application of this model to predict side effects may enhance SSRI precision dosing strategies in youth.

A pilot, single-arm feasibility study of an integrated cognitive-behavioral treatment for anxiety in young autistic children.

Anxiety is prevalent in young autistic children under 7 years of age. Yet there is a paucity of empirically based interventions for this age group. DINO Strategies for Anxiety and Uncertainty Reduction (DINOSAUR) is an innovative cognitive behavioral intervention that seeks to optimize treatment response in young autistic children by targeting anxiety and the contributing mechanisms of intolerance of uncertainty and parental accommodation using a telehealth delivery model. This pilot, single-arm study examines the preliminary feasibility of DINOSAUR. Fourteen autistic children ages 4-6 years with average language and cognitive skills and their parents received the intervention. Quantitative and qualitative data pertaining to parent satisfaction and treatment outcomes were collected. Attendance, retention, and parent satisfaction ratings offer preliminary support for the feasibility of the treatment model. Change in clinical severity ratings on a semi-structured parent interview of anxiety and parents' qualitative report suggests the potential to benefit young autistic children. Results support future study of the DINOSAUR model in a larger, randomized controlled trial.

Treating child anxiety using family-based internet delivered cognitive behavior therapy with brief therapist guidance: A randomized controlled trial

Online treatment delivery has the potential to increase access to evidence-based mental health care for children with anxiety disorders. Using a randomized controlled trial design, we evaluated the efficacy of Cool Kids Online, a family-based and therapist supported internet-delivered cognitive behavioral treatment (CBT) designed to target anxiety disorders in children. Ninety-five children aged 7–12 years with a DSM-5 anxiety disorder were randomly allocated to Cool Kids Online or a waitlist control. Children were assessed at baseline, week 11, and 6-months following treatment. Children in waitlist received treatment after week 11 and also completed assessments immediately and six months after treatment, allowing treatment maintenance to be evaluated for all children. Compared to waitlist, Cool Kids Online led to significantly greater remission of anxiety disorders (primary and all anxiety diagnoses) and greater reduction of caregiver-reported anxiety symptoms and interference at week 11. Child-reported anxiety symptoms and interference and child- and caregiver-reported depressive or externalizing symptoms did not differ significantly between conditions. Medium to large within-treatment effects were observed for all children from pre to post treatment with post treatment effects maintained until follow-up. Overall, the findings provide support for the efficacy of the program in treating anxiety. Cool Kids Online compared to waitlist for the remission of anxiety disorders in clinically anxious children; anzctr.org.au; ACTRN12615000947505.

Pediatric anxiety disorders: Basic concepts for primary care.

Anxiety disorders in children and adolescents often present in primary care, and many clinicians will need to guide families on treatment. The purpose of this article is to give a brief overview of assessment and treatment principles for clinicians in primary care. Anxiety and its expression are heavily influenced by children's developmental progression and capabilities. Anxiety disorders have multiple underlying etiologies including temperament, environmental exposure to stressors, and childhood trauma. All anxiety disorders are strengthened by an operant process known as escape conditioning. The most effective treatments for child and adolescent anxiety begin with behavioral-based interventions including exposure with response prevention (ERP) and cognitive behavioral therapy (CBT). Medication can be effective in combination with CBT and ERP, or as a standalone treatment when behavioral interventions are not available. Selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors have been evaluated by randomized clinical trials for the treatment of childhood anxiety, but most are not approved by the Food and Drug Administration. When anxiety is severe and functional impairment is high, referral for psychiatric care and multimodal treatment reduces the likelihood of poor outcomes.

Immersive Virtual Reality Exposures for the Treatment of Childhood Anxiety.

Exposure-based cognitive behavior therapy (CBT) has demonstrated efficacy and is recommended as a front-line treatment for childhood anxiety. Unfortunately, challenges exist that impact the effective implementation of exposure-based CBT in clinical practice. One of the primary challenges is the accessibility and availability of exposure stimuli (e.g., spiders, storms, heights) in CBT sessions. Immersive virtual reality (VR) has shown promise as a scalable and sustainable solution to address this clinical need, but remains largely untested in youth with anxiety disorders. Here, we examine the use of VR exposures in the treatment of youth with an anxiety disorder (i.e., specific phobias). We aimed to investigate: (1) the feasibility and clinical benefit of VR exposures; (2) whether VR exposures elicit changes in physiological arousal and/or subjective distress; and (3) whether habituation serves as a mechanism across physiological and subjective outcomes for VR exposures. Three youth and their parents completed a clinical evaluation, which was followed by a one session treatment (OST) with VR exposures. Afterward, youth and parents completed clinical assessments one-week and 1-month after treatment. Immersive VR exposures were found to be feasible and demonstrated clinical benefit for reducing anxiety severity. Additionally, VR exposures elicited changes in both physiological and subjective outcomes. Finally, physiological habituation to VR exposures was observed among participants who exhibited treatment response at follow-up. Collectively, these findings demonstrate preliminary evidence that VR exposures are feasible, tolerable, and show some therapeutic benefit for treating youth with anxiety.

Treatment motivation in child anxiety treatment – Factor structure and associations with outcomes

Motivation is associated with cognitive behavioral treatment (CBT) outcomes. We examined the factor structure of a motivation measure, and if motivation factors were differentially associated with CBT outcomes for children with anxiety. The sample comprised 179 children aged 8–15 years (M age = 11.5 years, SD = 2.1; 53.0% girls) with anxiety disorders who received CBT in a randomized controlled community clinic trial. Participants completed the Nijmegen Motivation List – child version (NML-C) at treatment onset. Outcomes were diagnostic recovery, anxiety/depression symptom and clinical severity change from pre-treatment to post-treatment, one-, and 3.9-years follow-up, and treatment dropout. Principal component analysis showed that the NML-C comprised two factors, preparedness (beliefs that CBT is useful and willingness to engage in treatment; 36.4% explained variance) and distress (discomfort from symptoms and perceived urgency to be helped; 12.7% explained variance). Higher preparedness predicted larger clinical severity reduction at post-treatment, alongside pre-treatment clinical severity. Higher distress predicted larger depression reduction at one-year follow-up, alongside pre-treatment depression. Higher preparedness predicted lower dropout. In conclusion, the NML-C comprises two factors that are differentially associated with CBT outcomes, but not above the effects of pre-treatment symptoms. Clinicians' focus on children's distress and preparedness could enhance CBT outcomes and reduce dropout.

Efficacy and safety of a daytime anxiolytic containing technologically processed antibodies to the S100 protein. Overview of clinical studies

The review presents the results of clinical studies of the efficacy and safety of Tenoten and Tenoten children’s in the treatment of anxiety, neurotic, stress-related and somatoform disorders and adjustment disorders. Technologically processed antibodies to the S100 protein in Tenoten and Tenoten children’s drugs change the conformation of the S100 protein, which is considered as a pathological link in the development of anxiety states, as well as neurodegenerative diseases. Tenoten is a well-studied daytime anxiolytic that combines a favorable safety profile with high anxiolytic activity. The efficacy of Tenoten in the treatment of anxiety disorders is comparable to that of benzodiazepine drugs. Tenoten has no inhibitory and muscle relaxant effects, does not cause drug tolerance, addiction, "withdrawal" syndrome, as well as drug interactions. Tenoten for children has been shown to be effective in the treatment of anxiety in children, including those with somatic manifestations, attention deficit hyperactivity disorder, and learning disabilities.

A Pilot Trial of SPACE (Supportive Parenting for Anxious Childhood Emotions) in Autism.

Family accommodation describes changes parents make to their behavior, intended to alleviate their child's distress, which stems from a psychopathology. In anxiety, studies show that accommodation alleviates distress in the short term but is associated with increased symptom severity, greater functional impairment, poorer treatment outcomes, increased caregiver burden and disruption to family functioning longitudinally. Research shows high prevalence of family accommodation of anxiety in autism. While the most common treatments for anxiety in autism are cognitive-behavior therapy and pharmacology, research is limited and other approaches must be considered. Supportive Parenting for Anxious Childhood Emotions (SPACE) is a parent-based, manualized treatment for anxiety targeting family accommodation, which has been found to be acceptable and efficacious in treating childhood anxiety. This pilot trial examined the feasibility, acceptability, treatment-satisfaction, and preliminary efficacy of SPACE for anxiety in autism. Parents of 15 autistic children (ages 6-10years) with at least average cognitive abilities exhibiting high levels of anxiety participated in 13 weekly sessions of SPACE. Feasibility and acceptability were assessed through enrollment, attrition rates, and adverse events. Of 26 eligible families, 22 (84.62%) elected to participate, 15 of whom (68.18%) completed treatment. Parents rated the treatment as highly satisfactory. Anxiety symptom severity and family accommodation were significantly reduced following treatment, with 86.66% of participants showing reliable change post-treatment, and this reduction was preserved at 2-month follow-up. This study provides preliminary evidence that SPACE is feasible, acceptable, satisfactory, and produces improvement in anxiety in the autistic population.Trial registration number: NCT04747262 Date of registration: February 10, 2021.

The mediating effect of math self-efficacy on the relationship between parenting style and math anxiety.

The present study aims to investigate the associations among math self-efficacy, parenting style, and math anxiety in primary school children. The sample comprised 400 participants, aged between 10 and 11 years old, from an elementary school in China. Participants completed three self-reported questionnaires on math anxiety, parenting styles and math self-efficacy. The results revealed that rejection was strongly and positively correlated with math anxiety, while emotional warmth was negatively related to math anxiety. Interestingly, math anxiety was found to be related to rejection, with math self-efficacy playing a mediating role in this relationship. Conversely, math self-efficacy played a mediating role in the relationship between parenting styles and math anxiety, while over protection exhibited no significant correlation with math anxiety. The study also showed that gender differences existed in the level of math anxiety and math self-efficacy, with boys exhibiting lower math anxiety and higher math self-efficacy than girls. These results provide important insights into the development and treatment of math anxiety in primary school children. Specifically, parents and educators should focus on enhancing children's math self-efficacy beliefs, while adopting a parenting style characterized by emotional warmth and low levels of rejection.

Oxytocin as a Biomarker of Differential Effects to SPACE vs. CBT Treatment of Child Anxiety Disorders

ABSTRACT Objective Two lines of research, on outcome moderators and on novel treatment targets, seek to improve the overall efficacy of child anxiety treatment, with mixed results. We propose that an integration of both lines of research can lead to improved treatment efficacy. In a first proof of concept of this approach, we studied whether the interaction between baseline levels and targeted changes in peripheral oxytocin (OT) can predict differential responses to two childhood anxiety treatments. Method A total of 124 mother-child dyads participated in the study. Children’s salivary OT levels were measured at baseline and again, immediately after an experimental dyadic interaction in the lab. Dyads were subsequently randomized to receive one of two treatments, differing in their targets: SPACE (Supportive Parenting for Anxious Childhood Emotions) and CBT (cognitive-behavioral therapy). Treatment outcomes were assessed using the Childhood Anxiety Related Emotional Disorders scale, reported by both mother and child. Results The findings suggest that in SPACE, where the mother is the main agent of change, higher baseline levels of child OT, coupled with increases in OT following a positive mother-child interaction, predicted greater treatment efficacy. By contrast, in CBT, where the child is the main agent of change, higher baseline levels of child OT, coupled with a decrease in OT following the interaction, predicted greater treatment efficacy. Conclusions The findings highlight the importance of the integration between moderators and targets of treatments for progress toward improving treatment efficacy through precision medicine.

The Effectiveness of Acceptance-and-Commitment-Based Parenting Training on Mood and Anxiety in Children and Self-compassion in Parents

Objective: Depression and anxiety are common in children and a major cause of many illnesses and disabilities in this age group; Moreover, parents have the greatest impact on shaping the mental health and well-being of their children and there is a vast literature describing the importance of parenting factors in the development of depression and anxiety in children. Methods: We used the experimental research design in this study. The sample consisted of 34 children with depression and anxiety who were randomly allocated into ACT on parenting (intervention) and control groups via the randomization method. The intervention group received eight 2-h sessions weekly. The revised child anxiety and depression scale, parent short versions and the self-compassion scale were administered in both groups. The analyses of covariance (ANCOVA) and the repeated measures of analysis of variance (ANOVA) were employed to determine the difference between the intervention and control groups on depression, anxiety, and self-compassion. Results: ANCOVA and repeated measures ANOVA results showed clinically significant changes in depression and anxiety in children and self-compassion in parents in the intervention group (P<0.001). The Mean±SD of depression in the intervention group was 16.50±0.89 at baseline, which significantly decreased to 2.94±3.27 at post-measure and 2.25±3.35 at follow-up (P<0.001). The Mean±SD of anxiety was 18.19±1.87, which significantly decreased to 7.63±4.34 at post-measure and 7.06±4.52 at follow-up (P<0.001). Additionally, the mean and SD score of self-compassion was 56.43±3.14 in pre-intervention, which significantly improved to 97.18±3.72 in post-intervention and 98.25±4.76 at follow-up (P<0.001). Conclusion: The results show that ACT-based parenting is an effective treatment for depression and anxiety in children. This method also improves self-compassion in parents.

Comparing the effectiveness of cognitive-behavioral therapy and parent-child interaction therapy on the anxiety and loneliness of children with separation anxiety disorder

Aim: The purpose of this study was to compare the effectiveness of cognitive-behavioral therapy and parent-child interaction therapy on the anxiety and loneliness of children with separation anxiety disorder. Methods: The current research was of the type of practical and quasi-experimental designs of pre-test-post-test and follow-up with a control group. The statistical population of this research included all children (girls and boys) suffering from separation anxiety disorder in Sari city in the first six months of 2021. The sample of this research includes 30 people who referred to Bammad Counseling Center and Bawar Counseling Center who were selected using available sampling method and randomly divided into two experimental groups of cognitive-behavioral therapy and parent-child interaction therapy and the control group in the list. They waited. The data were obtained using the Spence Children's Anxiety Scale (1997) and Asher et al.'s (1984) Loneliness Questionnaire. The data was analyzed using the method of analysis of variance with repeated measurements and SPSS-26 software. Results: The results showed that there is a significant difference between the two groups of cognitive-behavioral therapy and parent-child interaction therapy on anxiety and loneliness in children with separation anxiety disorder, and cognitive-behavioral therapy causes more changes in anxiety in children. He was diagnosed with separation anxiety disorder and this treatment is stronger than parent-child interaction therapy in this group of patients. However, according to the average indices and the effect size obtained in the treatment of parent-child interaction, it caused more changes in loneliness in children with separation anxiety disorder, and this treatment is stronger than cognitive-behavioral therapy in this group of children with separation anxiety disorder. It was separation anxiety disorder (P<0.001). Conclusion: Therefore, it can be concluded that cognitive-behavioral treatment of anxiety in children with separation anxiety disorder and parent-child interaction therapy can be an effective intervention method to improve the loneliness of children with separation anxiety disorder.

A randomised controlled trial to compare clinical and cost-effectiveness of an online parent-led treatment for child anxiety problems with usual care in the context of COVID-19 delivered in Child and Adolescent Mental Health Services in the UK (Co-CAT): a study protocol for a randomised controlled trial

BackgroundIn the context of COVID-19, NHS Child and Adolescent Mental Health Services (CAMHS) and other children’s mental health services have faced major challenges in providing psychological treatments that (i) work when delivered remotely and (ii) can be delivered efficiently to manage increases in referrals as social distancing measures have been relaxed. Anxiety problems are a common reason for referral to CAMHS, children with pre-existing anxiety problems are particularly vulnerable in the context of COVID-19, and there were concerns about increases in childhood anxiety as schools reopened. The proposed research will evaluate the clinical and cost-effectiveness of a brief online parent-led cognitive behavioural treatment (CBT) delivered by the OSI (Online Support and Intervention for child anxiety) platform with remote support from a CAMHS therapist compared to ‘COVID-19 treatment as usual’ (C-TAU) in CAMHS and other children’s mental health services throughout the COVID-19 pandemic.MethodsWe will conduct a two-arm, multi-site, randomised controlled non-inferiority trial to evaluate the clinical and cost-effectiveness of OSI with therapist support compared to CAMHS and other child mental health services ‘COVID-19 treatment as usual’ (C-TAU) during the COVID-19 outbreak and to explore parent and therapists’ experiences.DiscussionIf non-inferiority is shown, the research will provide (1) a solution for efficient psychological treatment for child anxiety disorders while social distancing (for the COVID-19 context and future pandemics); (2) an efficient means of treatment delivery as ‘normal service’ resumes to enable CAMHS to cope with the anticipated increase in referrals; and (3) a demonstration of rapid, high-quality evaluation and application of online interventions within NHS CAMHS to drive forward much-needed further digital innovation and evaluation in CAMHS settings. The primary beneficiaries will be children with anxiety disorders and their families, NHS CAMHS teams, and commissioners who will access a potentially effective, cost-effective, and efficient treatment for child anxiety problems.Trial registrationISRCTN ISRCTN12890382. Registered prospectively on 23 October 2020.

67.4 SPACE: A Parent-Based Treatment for Child Anxiety and OCD

In recent years, there has been rapidly increasing interest in the construct of family accommodation in anxiety disorders, generating data on the underlying theoretical mechanisms, associations with anxiety disorders, and intervention research. Today, family accommodation is considered a key factor impacting child anxiety. Family accommodation of child’s anxiety refers to changes that parents make in their own behavior to help their child avoid or alleviate distress related to the anxiety disorder.

Exercise for the treatment of anxiety in children and adolescents

Exercise for the treatment of anxiety in children and adolescents

Mitigating Multiple Sources of Bias in a Quasi-Experimental Integrative Data Analysis: Does Treating Childhood Anxiety Prevent Substance Use Disorders in Late Adolescence/Young Adulthood?

Psychiatric epidemiologists, developmental psychopathologists, prevention scientists, and treatment researchers have long speculated that treating child anxiety disorders could prevent alcohol and other drug use disorders in young adulthood. A primary challenge in examining long-term effects of anxiety disorder treatment from randomized controlled trials is that all participants receive an immediate or delayed study-related treatment prior to long-term follow-up assessment. Thus, if a long-term follow-up is conducted, a comparison condition no longer exists within the trial. Quasi-experimental designs (QEDs) pairing such clinical samples with comparable untreated epidemiological samples offer a method of addressing this challenge. Selection bias, often a concern in QEDs, can be mitigated by propensity score weighting. A second challenge may arise because the clinical and epidemiological studies may not have used identical measures, necessitating Integrative Data Analysis (IDA) for measure harmonization and scale score estimation. The present study uses a combination of propensity score weighting, zero-inflated mixture moderated nonlinear factor analysis (ZIM-MNLFA), and potential outcomes mediation in a child anxiety treatment QED/IDA (n = 396). Under propensity score-weighted potential outcomes mediation, CBT led to reductions in substance use disorder severity, the effects of which were mediated by reductions in anxiety severity in young adulthood. Sensitivity analyses highlighted the importance of attending to multiple types of bias. This study illustrates how hybrid QED/IDAs can be used in secondary prevention contexts for improved measurement and causal inference, particularly when control participants in clinical trials receive study-related treatment prior to long-term assessment.

Single-Session Computer-Delivered Intervention for Parental Accommodation and Overcontrolling Behaviors: A Pilot Study

ABSTRACT Despite repeated calls regarding the need to target parental accommodation and overcontrol in child anxiety treatment, brief protocols specifically targeting these behaviors in parents of clinically anxious youth are currently limited in number. The present investigation piloted and refined a theoretically informed, internet-delivered, single-session intervention (SSI) specifically aimed at reducing parental accommodation and overcontrolling behaviors. Socioeconomically and racially diverse parents of clinically anxious children (N = 12; M age =10.08 years, SD = 1.74, range = 7–14 years) were recruited in two phases. In Phase One, three online focus groups with two parents each (n = 6) received the intervention and provided qualitative and quantitative feedback on the feasibility and acceptability of the intervention program. Parental feedback from the focus groups was used to revise the program. In Phase Two, the revised program was administered to six new parents to examine the program’s acceptability and feasibility for increasing psychoeducational knowledge regarding child anxiety, parental accommodation, and overcontrol. Across both phases, the intervention was well-received by parents in terms of relevance, acceptability, and feasibility. Parents demonstrated significant increases in knowledge of parental accommodation, overcontrol, and child anxiety from pre- to post-intervention. Qualitative data indicated that parents benefited from the unique online format as well as the content. Findings support the feasibility and acceptability of an accessible and time-efficient SSI designed to target problematic parenting behaviors among parents of clinically anxious children.

Online Support and Intervention for Child Anxiety (OSI): Development and Usability Testing.

BackgroundInternet-based treatments for child anxiety may help to increase access to evidence-based therapies; however, user engagement, uptake, and adherence within routine clinical practice remain as challenges. Involving the intended end users in the development process through user-centered design and usability testing is crucial for maximizing user engagement and adoption of internet-based treatments, but so far this has been lacking for internet-based treatments for child anxiety.ObjectiveThe aim of this study is to develop an internet-based treatment for child anxiety through a process of user-centered design (phase 1) and usability testing (phase 2), based on an existing evidence-based, face-to-face, therapist-supported, parent-led cognitive behavioral therapy intervention. It is intended that the internet-based version of this treatment would consist of a parent website, case management system for clinicians, and mobile game app for children.MethodsParents, children, and clinicians who were familiar with the face-to-face version of the treatment were recruited from 2 National Health Service clinics. In phase 1, participants participated in 3 workshops to gain feedback on the overall concept, explore their wants and needs for the websites and game, generate ideas on how the treatment may look, and gain feedback on initial mock-ups of the websites and game. In phase 2, participants attended 3 individual usability testing sessions where they were presented with working prototypes of the website or game and asked to perform a series of tasks on the website (parents and clinicians) or play the game (children). The frequency and details on usability errors were recorded. Participants were asked for their feedback on the website and game using a standardized usability questionnaire and semistructured interviews. The websites and game were iterated after each round of usability testing in response to this feedback.ResultsIn phase 1, participants approved the general concept and rated the initial mock-ups of the website and game positively. In phase 2, working prototypes were rated positively and usability errors declined across the iterations and were mainly cosmetic or minor issues relating to esthetic preference, with few issues regarding ability to navigate the website or technical issues affecting functionality. Feedback from the semistructured interviews further supported the positive response of participants to the website and game, and helped identify areas for improvement during the iteration process. The final iteration of the website and game are presented.ConclusionsTaking an iterative approach to development through user-centered design and usability testing has resulted in an internet-based treatment for child anxiety (Online Support and Intervention for child anxiety) that appears to meet the needs and expectations of the intended users (parents, children, and clinicians) and is easy and enjoyable to use.

A randomized double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in children and adolescents with autism spectrum disorder.

This study was a 10-week double-blind, placebo-controlled pilot trial of mirtazapine for anxiety in youth with autism spectrum disorder (ASD). Participants were ages 5 to 17 years with ASD and clinically significant anxiety (Pediatric Anxiety Rating Scale [PARS] score ≥10). Thirty participants were randomized to mirtazapine (7.5-45 mg/day) or placebo in a 2:1 ratio. The co-primary outcome measures were the PARS and the Clinical Global Impressions-Improvement subscale (CGI-I). Mirtazapine resulted in a statistically significant within group decrease in anxiety on the PARS (ES 1.76, p < 0.001). The improvement in PARS score for mirtazapine versus placebo was clinically meaningful but not statistically significant (ES = 0.63, p = 0.64). Forty-seven percent of participants assigned to mirtazapine (95% CI 22%: 74%) and 20% assigned to placebo (95% CI 2%: 60%) were rated "much improved" (CGI-I = 2) or "very much improved" (CGI-I = 1) for anxiety, p = 0.46. No statistically significant differences in mean 10-week changes between mirtazapine and placebo occurred on any outcome measure. There were no statistically significant differences in adverse effect frequency between mirtazapine and placebo. The results are consistent with mirtazapine's safety and tolerability and meet three of four pre-specified indicators of efficacy (statistically significant change in total PARS score for mirtazapine, numerically greater reduction in total PARS score for mirtazapine than placebo, numerically higher number of responders to mirtazapine than placebo, but not greater than 50% of participants receiving mirtazapine rated as responders). Implementation of a larger randomized controlled trial of mirtazapine for the treatment of anxiety in this population is supported.Clinical trial registration information: Mirtazapine Treatment of Anxiety in Children and Adolescents with Pervasive Developmental Disorders; https://clinicaltrials.gov ; NCT01302964.