Video-Delivered Family Therapy for Perinatal Women With Depressive Symptoms and Family Conflict: Feasibility, Acceptability, Safety, and Tolerability Results From a Pilot Randomized Trial.

BACKGROUND: Although individual-level treatments exist for pregnant and postpartum women with depression, family conflict is a significant factor that can contribute to the development and severity of perinatal depressive symptoms. Yet, there is a lack of research on family therapy for perinatal women with moderate to severe depressive symptoms and family conflict. Further, research is needed on the feasibility, acceptability, safety, and tolerability of family therapies for perinatal depression that are delivered using Health Insurance Portability and Accountability Act-compliant videoconferencing technology (VCT). OBJECTIVE: This paper describes the feasibility, acceptability, safety, and tolerability of a VCT-based family therapeutic intervention, Resilience Enhancement Skills Training (REST), for perinatal women with moderate to severe depressive symptoms and moderate to high conflict with their family members. METHODS: This paper includes data from an ongoing randomized trial that compares an experimental family therapeutic intervention (REST) to standard of care (VCT-based problem-solving individual therapy) for the treatment of moderate to severe depressive symptoms in perinatal women with moderate to high family conflict. Both interventions were delivered by masters-level therapists using VCT. A total of 83 perinatal women and their adult family members (N=166 individuals) were recruited for participation in the study. Feasibility, defined as therapist adherence to ≥80% of REST session content, was assessed in audio-recorded sessions by 2 expert raters. Acceptability was defined as ≥80% of families completing REST, including completion of ≥80% homework assignments and family report of satisfaction with REST. Completion of REST was assessed by review of therapist session notes, and satisfaction was assessed by participant completion of a web-based questionnaire. The Beck Depression Inventory-Second Edition was administered to perinatal women by research assistants (blind to study group assignment) to assess safety, defined as a reduction in depressive symptoms during the treatment phase. The Family Environment Scale-Family Conflict subscale was administered by therapists to participants during the treatment phase to assess tolerability, defined as a reduction in family conflict during the treatment phase. RESULTS: On average, the therapists achieved 90% adherence to REST session content. Of the families who started REST, 84% (32/38) of them completed REST, and on average, they completed 89% (8/9) of the homework assignments. Families reported satisfaction with REST. The results showed that REST is safe for perinatal women with moderate to severe depressive symptoms, and none discontinued due to worsened depressive symptoms. The results showed that REST is well tolerated by families, and no families discontinued due to sustained family conflict. CONCLUSIONS: The results show that REST is feasible, acceptable, safe, and tolerable for families. These findings will guide our interpretation of REST's preliminary effectiveness upon completion of outcome data collection. TRIAL REGISTRATION: ClinicalTrials.gov NCT04741776; https://clinicaltrials.gov/ct2/show/NCT04741776.

Citalopram Did Not Significantly Improve Anxiety in Children with Autism Spectrum Disorder Undergoing Treatment for Core Symptoms: Secondary Analysis of a Trial to Reduce Repetitive Behaviors.

Objective: Anxiety disorders are among the most common co-occurring conditions in autism spectrum disorder (ASD). Despite their prevalence and impact, there are no randomized controlled trials (RCTs) aimed at evaluating the efficacy of selective serotonin reuptake inhibitors (SSRIs) for anxiolysis in this population, who may have a different biological basis for anxiety. Methods: Secondary analyses of the STAART double-blind, placebo-controlled RCT of citalopram in children with ASD examined whether citalopram reduced anxiety measured on the parent-reported Child and Adolescent Symptom Inventory-4 (CASI-4) as the primary outcome. An intention-to-treat analysis involving all 149 participants used multiple imputations for missing data and included baseline stratification factors of age group and site, among others. We prespecified as clinically significant a 33% reduction in anxiety in citalopram versus placebo, coinciding with 80% power. We tested whether communicative ability on the Vineland Communication score moderated treatment effect and explored whether initial anxiety was associated with greater adverse events, which could impact on dose titration and achieving optimal dose. Results: Both groups showed substantial reduction in anxiety. Citalopram was associated with a nonsignificant 16.5% greater reduction (observed coefficient = -0.181, bootstrap standard error = 0.126, p = 0.151, confidence interval = -0.428 to 0.066). Anxiety reports were significantly lower in children with reduced communicative ability, but communicative ability did not moderate the treatment effect (interaction p = 0.294). Initial anxiety levels were not associated with increased adverse effects (interaction ps 0.162-0.954). Conclusion: Citalopram did not statistically significantly improve anxiety in children with ASD. Clinicians should be cautious in their use of SSRIs for this indication. There remains a need for well-powered clinical trials testing the efficacy of SSRIs among autistic children with anxiety disorders.

International Interprofessional Collaborative Office Rounds (iiCOR): Addressing Children's Developmental, Behavioral, and Emotional Health Using Distance Technology.

Developmental, behavioral, and emotional issues are highly prevalent among children across the globe. Among children living in low- and middle-income countries, these conditions are leading contributors to the global burden of disease. A lack of skilled professionals limits developmental and mental health care services to affected children globally. Collaborative Office Rounds are interprofessional groups that meet regularly to discuss actual cases from the participants' practices using a non-hierarchical, peer-mentoring approach. In 2017, International Interprofessional Collaborative Office Rounds was launched with several goals: to improve the knowledge and skills of practicing child health professionals in high and low resourced settings regarding developmental and mental health care, to support trainees and clinicians in caring for these children, and to promote best practice in diagnosis and management of these conditions. Five nodes, each comprised of 3-4 different sites with an interprofessional team, from 8 countries in North America, Africa, Asia, and South America met monthly via videoconferencing. This report describes and evaluates the first 2 years' experience. Baseline surveys from participants (N = 141) found that 13 disciplines were represented. Qualitative analysis of 51 discussed cases, revealed that all cases were highly complex. More than half of the cases (N = 26) discussed children with autism or traits of autism and almost all (N = 49) had three or more themes discussed. Frequently occurring themes included social determinants of health (N = 31), psychiatric co-morbidity (N = 31), aggression and self-injury (N = 25), differences with the healthcare provider (N = 17), cultural variation in accepting diagnosis or treatment (N = 19), and guidance on gender and sexuality issues (N = 8). Participants generally sought recommendations on next steps in clinical care or management. A survey of participants after year 1 (N = 47) revealed that 87% (N = 41) had expectations that were completely or mostly met by the program. Our experience of regular meetings of interprofessional groups from different countries using distance-learning technology allowed participants to share on overlapping challenges, meet continuing educational needs while learning about different approaches in high- and low-resourced settings. International Interprofessional Collaborative Office Rounds may prove a useful strategy for increasing the work force capacity for addressing developmental, behavioral, and emotional conditions worldwide. More systematic studies are needed.

Predictors of Caregiver Strain for Parents of Children with Autism Spectrum Disorder.

Parents of children with autism spectrum disorder (ASD) face higher levels of caregiver strain compared to parents of children with other disabilities. This study examined child clinical features that predict high levels of caregiver strain for 374 parents of children with ASD. Caregiver strain was measured using the Caregiver Strain Questionnaire (CGSQ) objective, subjective internalized, and subjective externalized subscales. Confirmatory factor analysis indicated an acceptable fit for the original CGSQ three-factor solution. The strongest child predictors across CGSQ subscales were: disruptive behavior for objective strain, autism severity and disruptive behavior for subjective internalized strain, and oppositional behavior and hyperactivity for subjective externalized strain. Individualized interventions that attend to specific elements of parental strain may reduce strain and improve family wellbeing.

Reference Correction: Video-Delivered Family Therapy for Home Visited Young Mothers With Perinatal Depressive Symptoms: Quasi-Experimental Implementation-Effectiveness Hybrid Trial.

[This corrects the article DOI: 10.2196/11513.].

Video-Delivered Family Therapy for Home Visited Young Mothers With Perinatal Depressive Symptoms: Quasi-Experimental Implementation-Effectiveness Hybrid Trial.

BACKGROUND: The Federal Maternal, Infant, and Early Childhood Home Visiting Program is a national child abuse prevention strategy that serves families at risk for child maltreatment throughout the United States. Significant portions of the clients are young mothers who screen positive for clinically significant perinatal depressive symptoms and experience relational discord that worsens their symptoms. Although home visitors refer those who screen positive for depression to community-based treatment, they infrequently obtain treatment because of multiple barriers. These barriers are compounded for home visited families in rural areas. OBJECTIVE: This pilot study aimed to explore the feasibility, acceptability, and effectiveness of a video-delivered family therapy intervention on reducing maternal depressive symptoms and improving family functioning and emotion regulation. METHODS: A total of 13 home visited families received the video-delivered family therapy intervention. This study included a historical comparison group of mothers (N=13) who were previously enrolled in home visiting and screened positive for clinically significant perinatal depressive symptoms but refused treatment. A licensed marriage and family therapist delivered the family therapy intervention using Health Insurance Portability and Accountability Act-compliant videoconferencing technology on a computer from an office. Families participated in sessions in their homes using cell phones, tablets, and computers equipped with microphones and video cameras. Outcomes were measured following the final therapy session (post intervention) and 2 months later (follow-up). Depressive symptom scores of mothers who received the video-delivered family therapy intervention were compared with those of mothers in the historical comparison group over a 6-month period. Univariate statistics and correlations were calculated to assess measures of feasibility. Percentages and qualitative thematic analysis were used to assess acceptability. Wilcoxon signed-rank tests were used to assess changes in maternal and family outcomes. RESULTS: No families dropped out of the study. All families reported that the technology was convenient and easy to use. All families reported high satisfaction with the video-delivered intervention. Nearly all families reported that they preferred video-delivered family therapy instead of clinic-based therapy. Therapeutic alliance was strong. Mothers demonstrated a statistically significant reduction in depressive symptoms (P=.001). When compared with mothers in the historical comparison group, those in the family therapy intervention showed a significant reduction in depressive symptoms (P=.001). Families demonstrated statistically significant improvements in family functioning (P=.02) and cognitive reappraisal (P=.004). CONCLUSIONS: This pilot study yielded preliminary findings that support the feasibility, acceptability, and effectiveness of the video-delivered family therapy intervention for underserved home visited families in rural areas. Our findings are very promising, but more research is needed to ultimately influence mental health practices and policies that pertain to video-delivered mental health interventions in unsupervised settings (eg, homes).

Atomoxetine treatment for pediatric patients with attention-deficit/hyperactivity disorder with comorbid anxiety disorder.

OBJECTIVE: Research suggests 25% to 35% of children with attention-deficit/hyperactivity disorder (ADHD) have comorbid anxiety disorders. This double-blind study compared atomoxetine with placebo for treating pediatric ADHD with comorbid anxiety, as measured by the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-PI) and the Pediatric Anxiety Rating Scale (PARS). METHOD: Patients (ages 8-17 years) meeting DSM-IV criteria for ADHD and generalized anxiety disorder, separation anxiety disorder, and/or social phobia were randomized to 12 weeks of atomoxetine (n = 87) or placebo (n = 89). ADHDRS-IV-PI and PARS total scores were analyzed using analysis of covariance last observation carried forward and repeated-measures analyses. RESULTS: Sixty-six patients in each group completed the study. Mean ADHDRS-IV-PI total score improved significantly for atomoxetine (n = 55; -10.5, SD 10.6) relative to placebo (n = 58; -1.4, SD 8.3; p < .001). Mean PARS total score also improved significantly for atomoxetine (n = 55; -5.5, SD 4.8) relative to placebo (n = 58; -3.2, SD 5.0; p = .011). CONCLUSIONS: Atomoxetine was efficacious in reducing ADHD symptoms in patients who have ADHD with comorbid anxiety and was well tolerated. There was also a significant reduction in independently assessed anxiety symptoms using both clinician-rated and self-rated measures, which merits further investigation. Results support consideration of atomoxetine for the treatment of ADHD in youths who have ADHD with comorbid anxiety disorder. CLINICAL TRIAL REGISTRATION INFORMATION: The LYBP study, on which this article is based, was not registered at clinicaltrials.gov because the last patient visit occurred before July 1, 2005. Results, however, are publicly posted at lillytrials.com and clinicalstudyresults.org. The unique study ID at both sites is 6477a.

An implementation-effectiveness hybrid trial of video-based family therapy for peripartum depression in home visited mothers: a protocol for a pilot trial.

BACKGROUND: The Federal Maternal, Infant, and Early Childhood Home Visiting (HV) Program serves over 100,000 vulnerable families at risk for child abuse in the USA and aims to improve many outcomes, including maternal mental health (HRSA's Federal Home Visiting Program: partnering with parents to help children succeed, 2017). Most clients are insured by Medicaid, and about 40% are adolescent mothers (pregnant and post-delivery) (The mother and infant home visiting program evaluation: early findings on the Maternal, Infant, and Early Childhood Home Visiting Program, 2015). Over a third of home-visited clients report peripartum depressive symptoms (The mother and infant home visiting program evaluation: early findings on the Maternal, Infant, and Early Childhood Home Visiting Program, 2015). Family conflict increases rates of peripartum depression in adolescent mothers (J Ped Health Care 21:289-98, 2007; J Emot Behav Disord 5:173-83, 1997; Fam Relat 47:395-402, 1998; Arch Ped Adolesc Med 150:64-9, 1996; Obstet Gynecol 110:134-40, 2007; Am Fam Physician 93:852-58, 2016). Although home visitors screen for depression and refer those with positive screens for treatment (The mother and infant home visiting program evaluation: early findings on the Maternal, Infant, and Early Childhood Home Visiting Program, 2015), home-visited mothers infrequently obtain treatment or do not complete it if they do obtain it (Curr Probl Ped Adolesc Health Care 46:124-9, 2016; Making a difference in the lives of children and families: the impacts of Early Head Start Programs on infants and toddlers and their families, 2002; Depression and low-income women: challenges for TANF and welfare-to-work policies and programs, 2001; Aggress Violent Behav 15:191-200, 2010) due to many barriers (e.g., lack of child care, lack of transportation, geographical distance) (Arch Gen Psychiatry 68:627-36, 2011). There is a need for a video-based, family-oriented treatment for peripartum depression that is integrated into home visiting and would bypass these barriers. This article outlines a protocol for a pilot study that will explore the feasibility and acceptability of implementing a family-based treatment, using HIPAA-compliant video-based communication technology, for adolescents with peripartum depressive symptoms within the context of home visiting. METHODS: This study protocol includes a description of an implementation-effectiveness hybrid trial design that will include 12 depressed adolescent mothers and their family members and a historical comparison group of 12 previously enrolled adolescent mothers. DISCUSSION: The study results will provide a clearer understanding of whether or not video-based, family-oriented treatment is feasible and acceptable to implement within the context of home visiting and with home-visited adolescents with peripartum depressive symptoms. The findings from this pilot study could serve as a catalyst for future research that influences mental health practices and policies. TRIAL REGISTRATION: NCT03282448, ClinicalTrials.gov date of registration 09/21/2017.

Sertraline in children and adolescents with major depressive disorder.

OBJECTIVE: To explore time to first response and time to first persistent response of sertraline versus placebo and compare these parameters between children (6-11 years old, n = 177) and adolescents (12-17 years old, n = 199) with major depressive disorder. METHOD: A 10-week placebo-controlled treatment was followed by a 24-week open-label sertraline treatment. The double-blind studies were not powered to detect efficacy differences between age groups. A post hoc analysis explored time to first response and first persistent response using the Children's Depression Rating Scale-Revised and Clinical Global Impressions-Improvement predefined criteria. RESULTS: There were no statistically significant differences in time to first response or first persistent response between sertraline and placebo in children, except for time to first response on Clinical Global Impressions-Improvement. Sertraline had a significantly faster time to first persistent response in adolescents compared to placebo. Within treatment groups, children had a significantly faster time to first response than adolescents, whether treated with placebo or sertraline, but not on time to first persistent response. Both age groups showed similar improvement over 34 weeks of treatment. CONCLUSION: In the double-blind studies, children and adolescents had different patterns of response with sertraline vs. placebo.

Long-term sertraline treatment of children and adolescents with major depressive disorder.

OBJECTIVE: The aim of this study was to assess the long-term safety, tolerability, and efficacy of sertraline 50-200 mg once-daily in children (6-11 year olds) and adolescents (12-18 year olds) with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of major depressive disorder (MDD). METHODS: This study consisted of a 24-week open-label observational study of children and adolescents who had completed either of two 10-week double-blind, placebo-controlled trials. The Children's Depression Rating Scale-Revised (CDRS-R) was the primary measure of efficacy. RESULTS: Two hundred ninety nine (299) patients completed the acute studies and were eligible for the extension study. Of these, 226 enrolled, but 5 did not receive treatment. Of 221 patients (107 children and 114 adolescents), 62.4% completed the study. The endpoint mean daily dose was 109.9 mg/day. The mean decrease in CDRS-R score from double-blind baseline was 34.8 points (p < 0.001), with patients showing continued improvement in CDRS-R scores regardless of which treatment they received in the double-blind studies. At endpoint, 86% of patients met CDRS-R responder and 58% CDRS-R remitter criteria. CONCLUSIONS: Sertraline appears to be well tolerated and safe over 24 weeks of treatment in children and adolescents with MDD. Children and adolescents treated with sertraline appear to have increased improvement over that seen in the first 10 weeks of treatment. These findings need confirmation in placebo-controlled studies.

Atomoxetine monotherapy compared with combination therapy for the treatment of ADHD: a retrospective chart review study.

OBJECTIVE: To analyze Clinical Global Impression-Severity (CGI-S) in ADHD patients treated with atomoxetine (ATX) monotherapy versus ATX combination therapy with another ADHD-indicated medication. METHODS: This was a 2-site retrospective observational chart review study of child and adult ADHD patients, not necessarily treatment naïve, but treated ≥50 days post baseline with an endpoint assessment. To adjust for measured confounders, monotherapy (n = 77) versus combination (n = 108) cohort comparisons were performed using propensity score stratification and adjusted ANCOVA. RESULTS: There were no significant baseline cohort differences after propensity stratification. CGI-S scores after a mean 264 days of treatment were not statistically significantly different between cohorts, with no cohort differences observed in any assessed symptom subcategory. The cohorts were similar in discontinuation due to any reason, adverse event, and lack of efficacy. CONCLUSION: ATX combination therapy showed no evidence of additional benefit over ATX monotherapy in the treatment of ADHD in a community-based setting.

Post-traumatic stress disorder in children and adolescents: epidemiology, diagnosis and treatment options.

Post-traumatic stress disorder (PTSD) is a common psychiatric condition in childhood and adolescence. Rates vary widely depending upon the type of trauma exposure. Interpersonal traumas, such as rape or physical abuse, are more likely to result in PTSD than exposure to natural or technological disaster. Clinical presentations are exceedingly complex and children with PTSD are at increased risk of having comorbid psychiatric diagnoses. Because of its complexity and frequent occurrence with other disorders, assessment of PTSD necessitates a broad-based evaluation utilizing multiple informations and structured instruments specific to the symptoms of PTSD in youth. Cognitive-behavioral therapy (CBT) is the treatment of first choice. Pharmacological agents for PTSD treatment have received little empirical investigation in childhood. Pharmacological treatment is used to target disabling symptoms of the disorder, which limit psychotherapy or life functioning, by helping children to tolerate working through distressful material in therapy and life. Pharmacological treatment should be based on a stepwise approach utilizing broad spectrum medications such as the selective serotonin reuptake inhibitors as first-line agents. Comorbid conditions should be identified and treated with appropriate medication or psychosocial interventions. Treatment algorithms are provided to guide rational medication strategies for children and adolescents with PTSD, subsyndromal PTSD, and in PTSD that is comorbid with other psychiatric conditions of childhood. Reduction in even one debilitating symptom of PTSD can improve a child's overall functioning across multiple domains.

Pharmacologic treatment approaches for children and adolescents with posttraumatic stress disorder.

Posttraumatic stress disorder is a common cause of morbidity in children and adolescents. The disorder in youth is similar to that in adults, with high rates of psychiatric comorbidity. Children seem to be more sensitive to the effects of trauma, and early life trauma exposure may induce a complex sequence of events that leads to the development of multiple psychiatric disorders in adulthood. The state of knowledge regarding medication treatments for children and adolescents is in the earliest stages of development. There are no well-conducted, randomized clinical trials to guide practitioners. Medication may play an important role in reducing debilitating symptoms of PTSD and providing a buffer for children while they confront difficult material in therapy and may help to improve their general functioning in day-to-day life. Given the various medications with potential usefulness in PTSD, it is helpful to use a stepwise approach to treatment. As a general principal, broad-spectrum agents, such as the SSRIs, are a good first choice. The SSRIs have efficacy in treating the core symptoms of PTSD and conditions such as the anxiety disorders and depression that commonly co-occur with PTSD. These agents also improve social and occupational functioning and an individual's perception of improved quality of life [41, 45, 46]. Although the SSRIs are generally effective for a broad spectrum of problems, clinicians should systematically monitor for the persistence of symptoms that do not respond to these agents. For example, despite significant improvements in core PTSD symptoms in one study that used sertraline, little improvement was seen in patients' comorbid anxiety and depressive symptoms [41]. This finding demonstrates the value of continuous symptom monitoring and shows that residual or comorbid symptoms may require a different medication to augment effective SSRI treatment for PTSD. A reasonable approach is to begin with a broad-spectrum agent, such as an SSRI, which should target anxiety, mood, and reexperiencing symptoms. Adrenergic agents, such as clonidine, used either alone or in combination with an SSRI may be useful when symptoms of hyperarousal and impulsivity are problematic. Supplementing with a mood stabilizer may be necessary in severe affective dyscontrol. Similarly, introduction of an atypical neuroleptic agent may be necessary in cases of severe self-injurious behavior, dissociation, psychosis, or aggression. Comorbid conditions such as ADHD should be targeted with pharmacotherapy known to be effective, such as psychostimulants or newer agents such as atomoxetine. Pharmacologic treatment of PTSD in childhood is one approach to alleviating the acute and chronic symptoms of the disorder. Despite the lack of well-designed, randomized, controlled trials that support efficacy, medication can be used in a rational and safe manner. Reduction in even one disabling symptom, such as insomnia or hyperarousal, may have a positive ripple effect on a child's overall functioning. Pharmacotherapy is typically used as one component of a more comprehensive multiple modality treatment package, including psychoeducation of the parent and child, focused exposure-based psychotherapy with adjunctive family therapy when indicated, and long-term booster interventions that use an admixture of psychodynamic, cognitive-behavioral, and pharmacologic interventions.

Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials.

CONTEXT: The efficacy, safety, and tolerability of selective serotonin reuptake inhibitors (SSRIs) in the treatment of adults with major depressive disorder (MDD) are well established. Comparatively few data are available on the effects of SSRIs in depressed children and adolescents. OBJECTIVE: To evaluate the efficacy and safety of sertraline compared with placebo in treatment of pediatric patients with MDD. DESIGN AND SETTING: Two multicenter randomized, double-blind, placebo-controlled trials were conducted at 53 hospital, general practice, and academic centers in the United States, India, Canada, Costa Rica, and Mexico between December 1999 and May 2001 and were pooled a priori. PARTICIPANTS: Three hundred seventy-six children and adolescents aged 6 to 17 years with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined MDD of at least moderate severity. INTERVENTION: Patients were randomly assigned to receive a flexible dosage (50-200 mg/d) of sertraline (n = 189) or matching placebo tablets (n = 187) for 10 weeks. MAIN OUTCOME MEASURES: Change from baseline in the Children's Depression Rating Scale-Revised (CDRS-R) Best Description of Child total score and reported adverse events. RESULTS: Sertraline-treated patients experienced statistically significantly greater improvement than placebo patients on the CDRS-R total score (mean change at week 10, -30.24 vs -25.83, respectively; P =.001; overall mean change, -22.84 vs -20.19, respectively; P =.007). Based on a 40% decrease in the adjusted CDRS-R total score at study end point, 69% of sertraline-treated patients compared with 59% of placebo patients were considered responders (P =.05). Sertraline treatment was generally well tolerated. Seventeen sertraline-treated patients (9%) and 5 placebo patients (3%) prematurely discontinued the study because of adverse events. Adverse events that occurred in at least 5% of sertraline-treated patients and with an incidence of at least twice that in placebo patients included diarrhea, vomiting, anorexia, and agitation. CONCLUSION: The results of this pooled analysis demonstrate that sertraline is an effective and well-tolerated short-term treatment for children and adolescents with MDD.

Baseline factors predicting placebo response to treatment in children and adolescents with autism spectrum disorders: a multisite randomized clinical trial.

IMPORTANCE: The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. OBJECTIVE: To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression-Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children's Yale-Brown Obsessive-Compulsive Scale. INTERVENTIONS: Twelve weeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopram was 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). MAIN OUTCOMES AND MEASURES: A positive response was defined as having a score of at least much improved on the Clinical Global Impression-Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale-Revised, and the Children's Yale-Brown Obsessive-Compulsive Scale). Family measures included the Caregiver Strain Questionnaire. RESULTS: Several baseline predictors of response were identified, and a principal component analysis yielded 3 composite measures (disruptive behavior, autism/mood, and caregiver strain) that significantly predicted response at week 12. Specifically, participants in the placebo group were significantly less likely than participants in the citalopram group to respond at week 12 if they entered the study more symptomatic on each of the 3 composite measures, and they were at least 2 times less likely to be responders. CONCLUSIONS AND RELEVANCE: This analysis suggests strategies that may be useful in anticipating and potentially mitigating the nonspecific response in randomized clinical trials of children and adolescents with autism spectrum disorders. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00086645.

Exploring the manifestations of anxiety in children with autism spectrum disorders.

This study explores the manifestation and measurement of anxiety symptoms in 415 children with ASDs on a 20-item, parent-rated, DSM-IV referenced anxiety scale. In both high and low-functioning children (IQ above vs. below 70), commonly endorsed items assessed restlessness, tension and sleep difficulties. Items requiring verbal expression of worry by the child were rarely endorsed. Higher anxiety was associated with functional language, IQ above 70 and higher scores on several other behavioral measures. Four underlying factors emerged: Generalized Anxiety, Separation Anxiety, Social Anxiety and Over-arousal. Our findings extend our understanding of anxiety across IQ in ASD and provide guidance for improving anxiety outcome measurement.

Application of mid-infrared spectroscopy to the development and transfer of a manufacturing process for an active pharmaceutical ingredient.

The use of in situ mid-infrared spectroscopy to support the development of a pharmaceutical manufacturing process is disclosed. Data on this two-stage telescoped reaction from several reaction scales (<50 mL to 1600 liters) and at multiple manufacturing locations is shown. In addition to providing data on both reactions in the telescope, the mid-IR data has been used to monitor an intermediate distillation operation and therefore it has been possible to profile the whole process. Data is also shown on aliquot addition during the first chemical transformation, which is used to check the instrumentation.

Design and subject characteristics in the federally-funded citalopram trial in children with pervasive developmental disorders.

The Studies to Advance Autism Research and Treatment Network conducted a randomized trial with citalopram in children with Pervasive developmental disorders (PDDs). We present the rationale, design and sample characteristics of the citalopram trial. Subjects (128 boys, 21 girls) had a mean age of 9.3 (±3.12) years; 132 (88.6%) were diagnosed with autistic disorder (4.7% with Asperger's Disorder; 6.7% with PDD-not otherwise specified). Less than half of the subjects were intellectually disabled; 117 (78.5%) were rated Moderate or Marked on the Clinical Global Impression for Severity. Study measures were similar to previous Research Units on Pediatric Psychopharmacology trials. Subjects in this trial were slightly older and more likely to have complaints of repetitive behavior than participants in RUPP trials.