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Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that manifests in childhood with symptoms of inattention, hyperactivity, and impulsivity. The symptoms must occur in more than one setting and cause an impairment in functioning. Attention-deficit/hyperactivity disorder is one of the most common neurobehavioral disorders of childhood and may persist into adulthood. The assessment for ADHD should include a clinical history, review of information about school functioning, and assessment of common comorbid psychiatric disorders. Children with ADHD may be unaware of their symptoms, highlighting the need for collateral information from parents and teachers. Treatment may involve behavioral/psychologic interventions, educational interventions, and medications. Behavioral interventions are the first-line approach for preschool-age children, while medication treatment should be considered the first-line approach for school-aged children and adolescents. Pharmacologic treatments include stimulant and nonstimulant medications.

Autism spectrum disorder (ASD) is a lifelong, highly heterogeneous neurodevelopmental disorder characterized by deficits in social communication and interaction as well as restricted, repetitive patterns of behavior, interests, or activities. The symptoms begin early in development but may not become apparent until social demands exceed abilities. The diagnostic assessment should include a medical assessment; evaluation by a clinician familiar with the signs/symptoms of ASD such as a developmental pediatrician, child psychiatrist, or child neurologist; neuropsychological testing to assess for comorbid intellectual disability; a speech and language evaluation; and an occupational therapy evaluation. There is no cure for ASD, but early diagnosis and intervention are associated with better functional outcomes. The treatment approach should be multidisciplinary and may include behavioral therapy, speech therapy, occupational therapy, and educational interventions. Pharmacologic treatment may be used to manage psychiatric comorbidities and maladaptive behaviors.

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.

High rates of children involved with the child welfare system are prescribed psychotropics. In response, federal legislation has mandated state child welfare agencies to develop policies to improve...

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. 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. 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. NCT03282448 , ClinicalTrials.gov date of registration 09/21/2017.

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).

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).

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.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.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.ATX combination therapy showed no evidence of additional benefit over ATX monotherapy in the treatment of ADHD in a community-based setting.

Data from 5 atomoxetine trials in pediatric outpatients with attention-deficit/hyperactivity disorder (ADHD) were divided into training and validation data sets to develop models predicting atomoxetine treatment response, using changes in individual ADHD Rating Scale (ADHD-RS) items early in treatment. Treatment response was predicted after 1 week by a ≥1-point score decrease in ADHD-RS item 15 (“easily distracted;” positive predictive values [PPVs]: 84.9%, 74.3%, and 73.3%; negative predictive values [NPVs]: 52.6%, 50.5%, and 46.3%; training and 2 validation data sets, respectively); after 2 to 3 weeks, by a ≥1-point score decrease in ADHD-RS item 1 (“fails to give close attention or makes careless mistakes;” PPV = 77.7% and 77.9%) and by the absence of a ≥1-point score decrease on ADHD-RS items 1 and 10 (“on the go;” NPV = 72.2% and 77.5%), or by the combination of items 1 and 10 (PPVs: 75.1% and 75.4%; NPVs: 72.2% and 77.5%; training and validation data sets, respectively).

The aim of this study was to assess predictors of placebo response in all available short-term, placebo-controlled trials of psychotropic drugs for children and adolescents with internalizing disorders, major depressive disorder (MDD), obsessive compulsive disorder (OCD,) and anxiety disorders (ANX) exclusive of OCD and posttraumatic stress disorder (PTSD).We reviewed the literature relevant to the use of psychotropic medication in children and adolescents with internalizing disorders, restricting our review to double-blind studies including a placebo arm. Placebo response, defined according to each trial's primary response outcome variable and Clinical Global Impressions-Improvement, when available, and potential predictive variables were extracted from 40 studies.From 1972 to 2007, we found 23 trials that evaluated the efficacy of psychotropic medication involving youth with MDD, 7 pertaining to youths with OCD, and 10 pertaining to youths with ANX (N = 2,533 patients in placebo arms). For all internalizing disorders combined, predictors of nonresponse to placebo were the percentage of Caucasian patients included in the study and the duration of the disorder: Both variables were negatively correlated with the percent of placebo responders. The type of disorder was found to predict the robustness of placebo response: (OCDANXMDD). For a subset of MDD studies, we found that baseline illness severity tended to be negatively correlated with placebo response. Finally, trial "success" was significantly associated with lower placebo response rate.Predictors of placebo response in internalizing disorders of youths parallel those in adult studies, with the exception of race. These predictors should be considered when designing placebo-controlled trials in youths to enhance findings of true drug-placebo differences.

Marshall is a 6-year-old child who displayed significant symptoms of hyperactivity, impulsivity, defiance, and temper tantrums since 2 years of age. Marshall lives with his mother, a single parent, and two siblings, ages 4 and 1. His problematic behavior, defiance, and argumentativeness were significant problems at home for his mother, which often made her late to work in the morning. These behaviors were also problematic in the evenings at dinnertime and at bedtime not only for his mother but also for the whole family. Marshall was also having social problems at school including being increasingly shunned by other children because of his aggressiveness and impulsivity as well as being defiant and argumentative with his teachers.His mother initially sought out her pediatrician, who indicated that Marshall was too young for medication and that better discipline techniques were necessary. Medical workup at that point was unrevealing of any significant condition responsible for Marshall's behavior. Marshall's mother continued to pursue a psychiatric evaluation for Marshall, and a formal psychiatric evaluation revealed diagnoses of attention-deficit/hyperactivity disorder (ADHD), combined type, and oppositional defiant disorder (ODD). Paper and pencil instruments were used including the Swanson, Nolan, and Pelham (SNAP) form for assessing ADHD and ODD symptoms. On the form, both Marshall's mother and teacher indicated that he was significantly elevated in both ADHD and ODD symptom domains, and target symptoms were identified: hyperactivity, impulsivity, short attention span, difficulty with follow through, defiance, argumentativeness, tantrums, and the beginnings of aggressiveness.

Objective To assess the long-term safety and tolerability of atomoxetine hydrochloride in children and adolescents with attention-deficit/hyperactivity disorder treated for ≥3 years. Method Data from 13 double-blind, placebo-controlled trials and 3 open-label extension studies were pooled. Outcome measures were patient-reported treatment-emergent adverse events (AEs); discontinuations due to AEs, serious AEs, and changes in body weight, height, vital signs, electrocardiogram, and hepatic function tests. Results In total, 714 patients were treated with atomoxetine for ≥3 years (mean follow-up 4.8 years [SD 1.1 years]), including a subset of 508 treated for ≥4 years (mean follow-up 5.3 years [SD 0.8 years]). Most subjects were younger than 12 years at entry (73.8%), male (78.4%), and white (88.9%). The mean final daily dose of atomoxetine was 1.35 mg/kg (SD 0.37 mg/kg). No new or unexpected AEs were observed compared with acute-phase treatment. Less than 6% of patients exhibited aggressive/hostile behaviors, and less than 1.6% reported suicidal ideation/behavior. No clinically significant effects were seen on growth rate, vital signs, or electrocardiographic parameters, and ≤2% of patients showed potentially clinically significant hepatic changes. Conclusion Atomoxetine was safe and well tolerated for children and adolescents with ≥3 and/or ≥4 years of treatment.

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. J. Am. Acad. Child Adolesc. Psychiatry , 2006;45(10):1162-1170.

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.

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.

Attention-deficit/hyperactivity disorder (ADHD), once considered to be a childhood disorder, is diagnosed in ~7 million adults in the United States, as reported by The National Comorbidity Study. Although it is now recognized that ADHD often persists into adulthood, the current diagnostic criteria is geared toward symptom identification in children. Symptoms of inattention, impulsivity, and hyperactivity evolve over the life cycle and present differently in adults. Further complicating diagnosis is that ADHD is associated with multiple functional impairments and comorbid psychiatric disorders. The Multi-Modal Treatment Study of ADHD reported that only 32% of the study population had ADHD alone; 29% had ADHD plus oppositional defiant disorder and/or conduct disorder, 14% had ADHD plus anxiety or depression, and 25% had all three disorders. Optimal treatment utilizes a multi-modal approach including behavioral treatments combined with pharmacologic treatment strategies. Food and Drug Administration-approved medications for ADHD include the stimulants and nonstimulants, although tricyclic antidepressants and bupropion are also commonly used.In this monograph, Craig L. Donnelly, MD, reviews the history of ADHD and discusses the pathophysiologic progression of childhood symptoms into those commonly exhibited by adults. Next, Frederick W. Reimherr, MD, reviews comorbidity of ADHD and describes the Utah Criteria as a method of diagnosing adults through recollection of childhood problems. Finally, Joel L. Young, MD, reviews treatment approaches to adult ADHD and its comorbid conditions.

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

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.

This chapter reviews the published literature on pharmacotherapy for PTSD with specific attention to randomized clinical trials. Specific agents reviewed include: antidepressants, antiadrenergic agents, glucocorticoids, anticonvulsants, D-cycloserine, benzodiazepines, and antipsychotics. The empirical evidence indicates that selective serotonin reuptake inhibitors and serotonin/norepinephrine reuptake inhibitors can be considered first line medications for PTSD. It also indicates that neither atypical antipsychotic agents nor benzodiazepines can be recommended at this time. Combined approaches are also reviewed in which pharmacotherapy is combined with psychotherapy or other medications. Important gaps in current knowledge are also considered.It is clear that pharmacotherapy remains an important clinical option because medications are effective; they are often useful for treating comorbid depression and other anxiety disorders; they are generally wellaccepted by patients; and, finally the availability of prescribing clinicians is much greater than the availability of qualified psychotherapists.

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.

Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders.To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders.National Institutes of Health-sponsored randomized controlled trial.Six academic centers, including Mount Sinai School of Medicine, North Shore-Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School.One hundred forty-nine volunteers 5 to 17 years old (mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram (n = 73) or placebo (n = 76). Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders.Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d).Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form.There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95% confidence interval, 0.61-1.51; P.99). There was no difference in score reduction on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline (mean [SD], -2.0 [3.4] points for the citalopram-treated group and -1.9 [2.5] points for the placebo group; P = .81). Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus.Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders. Trial Registration clinicaltrials.gov Identifier: NCT00086645.

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).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.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 (p0.001), 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.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.

We explored the feasibility of realtime telemedicine in Croatia using Internet videoconferencing. A 33 kbit/s link was established between a team of specialists in the General Hospital 'Sveti Duh' in Zagreb and a general practitioner's clinic in Selca, on the island of Brač. During a two-week study, 16 patients (median age 51 years) were studied. Twenty-one teleconsultations (seven initial and 14 follow-up visits) were conducted, 13 with a specialist in internal medicine, six with a surgeon and two with a neurologist. In 18 cases (86%) telemedicine successfully replaced hands-on examination. The mean duration of the teleconsultations was 7.2 min (initial visits 7.4 min, follow-up visits 7.1 min). Each computer system cost about US$700. The total connection cost for the study was US$4.95. The teleconsultations saved the patients US$272 in travel costs. We suggest forming a permanent on-line specialist service connected to networked clinics via the Internet to improve access to health-care in Croatia.

To review the current knowledge of pharmacotherapy in the treatment of Post-traumatic Stress Disorder (PTSD) as it applies to children and adolescents and to provide a rational approach to medication use in Pediatric PTSD.The literature on the psychopharmacology of Pediatric PTSD is reviewed. Additionally, literature is reviewed on the neurobiological systems presumptively involved in trauma as well as studies in the pharmacology of adult PTSD, as they pertain to the treatment of Pediatric PTSD.There are too few studies in the current Pediatric PTSD literature to confirm treatment recommendations. Downward extrapolation from the adult literature combined with an understanding of the neurobiology of PTSD and its comorbid conditions may serve as the basis for a rational pharmacotherapy of PTSD in childhood. The effectiveness of targeting pharmacological agents at PTSD symptom clusters and associated comorbid conditions remains to be verified in controlled clinical trials.The state of psychopharmacology for Pediatric PTSD is in its earliest stages. While there are insufficient numbers of controlled pharmacological trials to make firm recommendations, the field requires a starting point for a rational psychopharmacological approach. Pharmacotherapy may provide symptom relief of both the debilitating primary symptoms and the comorbid conditions in children suffering from PTSD.

The development of acute neuropsychiatric symptoms in a 10-year-old boy subsequent to his return from travel abroad in Africa, where he had taken the antimalarial agent mefloquine (Lariam®), is reported. A 4-week course of cognitive-behavioral therapy was used to effectively treat this substance-induced anxiety disorder, which had been caused by treatment with mefloquine. A review of the literature about adverse neuropsychiatric effects of mefloquine and the differential diagnosis of malaria is provided. In an age in which international travel is occurring with increasing frequency, it is important to obtain travel histories, including exposure to prophylactic medication, when patients present with acute-onset psychiatric symptoms.

Ten men inpatients who met DSM-III-R criteria for schizophrenia participated. On five occasions at least one week apart, each subject had an intravenous line placed at 0730 after an overnight fast. On each occasion blood samples were drawn at 0800 and hourly thereafter through 1200 noon for measurement of plasma homovanillic acid (HVA). Total four-hour urine collections were obtained for measurement of urinary HVA. Subjects received five experimental conditions, in randomized sequence: no intervention, smoking one cigarette per hour, drinking one caffeinated cola per hour, lorazepam 2 mg IV push, or a high monoamine meal. Baseline (0800) plasma HVA measures showed only minor intrinsic variability. The average standard deviation in baseline plasma HVA over five occasions of measurement was low relative to the changes in HVA produced during treatment with antipsychotic medications. The high monoamine meal significantly elevated plasma HVA, with a similar trend for urinary HVA. Neither caffeine, nicotine, nor lorazepam significantly affected plasma or urinary HVA.

ContextThe 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.ObjectiveTo evaluate the efficacy and safety of sertraline compared with placebo in treatment of pediatric patients with MDD.Design and SettingTwo 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.ParticipantsThree 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.InterventionPatients 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 MeasuresChange from baseline in the Children's Depression Rating Scale–Revised (CDRS-R) Best Description of Child total score and reported adverse events.ResultsSertraline-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.ConclusionThe results of this pooled analysis demonstrate that sertraline is an effective and well-tolerated short-term treatment for children and adolescents with MDD.