Joel Sherrill

Cognitive Behavioral Therapy, Sertraline, or a Combination in Childhood Anxiety

BACKGROUND Anxiety disorders are common psychiatric conditions affecting children and adolescents. Although cognitive behavioral therapy and selective serotonin-reuptake inhibitors have shown efficacy in treating these disorders, little is known about their relative or combined efficacy. METHODS In this randomized, controlled trial, we assigned 488 children between the ages of 7 and 17 years who had a primary diagnosis of separation anxiety disorder, generalized anxiety disorder, or social phobia to receive 14 sessions of cognitive behavioral therapy, sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive behavioral therapy, or a placebo drug for 12 weeks in a 2:2:2:1 ratio. We administered categorical and dimensional ratings of anxiety severity and impairment at baseline and at weeks 4, 8, and 12. RESULTS The percentages of children who were rated as very much or much improved on the Clinician Global Impression-Improvement scale were 80.7% for combination therapy (P<0.001), 59.7% for cognitive behavioral therapy (P<0.001), and 54.9% for sertraline (P<0.001); all therapies were superior to placebo (23.7%). Combination therapy was superior to both monotherapies (P<0.001). Results on the Pediatric Anxiety Rating Scale documented a similar magnitude and pattern of response; combination therapy had a greater response than cognitive behavioral therapy, which was equivalent to sertraline, and all therapies were superior to placebo. Adverse events, including suicidal and homicidal ideation, were no more frequent in the sertraline group than in the placebo group. No child attempted suicide. There was less insomnia, fatigue, sedation, and restlessness associated with cognitive behavioral therapy than with sertraline. CONCLUSIONS Both cognitive behavioral therapy and sertraline reduced the severity of anxiety in children with anxiety disorders; a combination of the two therapies had a superior response rate. (ClinicalTrials.gov number, NCT00052078.)

Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods

ObjectiveTo present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents.MethodsFollowing a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described.ResultsCAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years) with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance.ConclusionsCAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI) treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results of CAMS will hold important implications for informing practice-relevant decisions regarding the initial treatment of youth with anxiety disorders.Trial registrationClinicalTrials.gov NCT00052078.

Clinical characteristics of anxiety disordered youth.

Reports the characteristics of a large, representative sample of treatment-seeking anxious youth (N=488). Participants, aged 7-17 years (mean 10.7 years), had a principal DSM-IV diagnosis of separation anxiety disorder (SAD), generalized anxiety disorder (GAD), or social phobia (SP). Although youth with a co-primary diagnosis for which a different disorder-specific treatment would be indicated (e.g., major depressive disorder, substance abuse) were not included, there were few other exclusion criteria. Participants and their parent/guardian underwent an extensive baseline assessment using a broad array of measures capturing diagnostic status, anxiety symptoms and severity, and areas of functional impairment. Means and standard deviations of the measures of psychopathology and data on diagnostic status are provided. The sample had moderate to severe anxiety disorder and was highly comorbid, with 55.3% of participants meeting criteria for at least one non-targeted DSM-IV disorder. Anxiety disorders in youth often do not present as a single/focused disorder: such disorders in youth overlap in symptoms and are highly comorbid among themselves.

Remission after Acute Treatment in Children and Adolescents with Anxiety Disorders: Findings from the CAMS.

OBJECTIVE To report on remission rates in anxious youth who participated in the Child/Adolescent Anxiety Multimodal Study (CAMS). The CAMS, a multisite clinical trial, randomized 488 children and adolescents (ages 7-17 years; 79% Caucasian; 50% female) with separation, social, and/or generalized anxiety disorder to a 12-week treatment of sertraline (SRT), cognitive behavioral therapy (CBT), their combination (COMB), or clinical management with pill placebo (PBO). METHOD The primary definition of remission was loss of all study-entry anxiety disorder diagnoses; additional definitions of remission were used. All outcomes were rated by independent evaluators blind to treatment assignment. Predictors of remission were also examined. RESULTS Remission rates after 12 weeks of treatment ranged from 46% to 68% for COMB, 34% to 46% for SRT, 20% to 46% for CBT, and 15% to 27% for PBO. Rates of remission (i.e., achieving a nearly symptom-free state) were significantly lower than rates of response (i.e., achieving a clinically meaningful improvement relative to baseline) for the entire sample. Youth who received COMB had significantly higher rates of remission compared to all other treatment groups. Both monotherapies had higher remission rates compared to PBO, but rates were not different from each other. Predictors of remission were younger age, nonminority status, lower baseline anxiety severity, absence of other internalizing disorders (e.g., anxiety, depression), and absence of social phobia. CONCLUSIONS For the majority of children, some symptoms of anxiety persisted, even among those showing improvement after 12 weeks of treatment, suggesting a need to augment or extend current treatments for some children.

Cognitive Training in Mental Disorders: Update and Future Directions

OBJECTIVE This article reviews the conceptual basis, definitions, and evolution of cognitive training approaches for the treatment of mental disorders. METHOD The authors review the current state of the knowledge on cognitive training in psychiatric illnesses, and its neural and behavioral targets, and summarize the factors that appear to relate to a successful response, including learner characteristics that influence clinical outcome. They also discuss methodological issues relevant to the development and testing of cognitive training approaches, with the goal of creating maximally efficient and effective approaches to training. Finally, they identify gaps in existing knowledge and outline key research directions for the future. RESULTS While much of the early research has been conducted in schizophrenia, cognitive training has more recently been applied to a widening range of neuropsychiatric illnesses, including attention deficit hyperactivity disorder, mood disorders, and substance use disorders. Cognitive training harnesses the inherent neuroplastic capacities of the brain, targeting neural system function across psychiatric disorders, thus improving the cognitive processes that play a role in emotion regulation, clinical symptoms, and adaptive community functioning. CONCLUSIONS Cognitive training offers considerable promise, especially given the limited efficacy of pharmacological interventions in ameliorating cognitive deficits. However, more research is needed to understand the mechanisms underlying cognitive training, predictors of response, generalization and real-world applicability, and approaches to dissemination in practice settings.

24- and 36-Week Outcomes for the Child/Adolescent Anxiety Multimodal Study (CAMS)

OBJECTIVE We report active treatment group differences on response and remission rates and changes in anxiety severity at weeks 24 and 36 for the Child/Adolescent Anxiety Multimodal Study (CAMS). METHOD CAMS youth (N = 488; 74% ≤ 12 years of age) with DSM-IV separation, generalized, or social anxiety disorder were randomized to 12 weeks of cognitive-behavioral therapy (CBT), sertraline (SRT), CBT+SRT (COMB), or medication management/pill placebo (PBO). Responders attended 6 monthly booster sessions in their assigned treatment arm; youth in COMB and SRT continued on their medication throughout this period. Efficacy of COMB, SRT, and CBT (n = 412) was assessed at 24 and 36 weeks postrandomization. Youth randomized to PBO (n = 76) were offered active CAMS treatment if nonresponsive at week 12 or over follow-up and were not included here. Independent evaluators blind to study condition assessed anxiety severity, functioning, and treatment response. Concomitant treatments were allowed but monitored over follow-up. RESULTS The majority (>80%) of acute responders maintained positive response at both weeks 24 and 36. Consistent with acute outcomes, COMB maintained advantage over CBT and SRT, which did not differ, on dimensional outcomes; the 3 treatments did not differ on most categorical outcomes over follow-up. Compared to COMB and CBT, youth in SRT obtained more concomitant psychosocial treatments, whereas those in SRT and CBT obtained more concomitant combined (medication plus psychosocial) treatment. CONCLUSIONS COMB maintained advantage over CBT and SRT on some measures over follow-up, whereas the 2 monotherapies remained indistinguishable. The observed convergence of COMB and monotherapy may be related to greater use of concomitant treatment during follow-up among youth receiving the monotherapies, although other explanations are possible. Although outcomes were variable, most CAMS-treated youth experienced sustained treatment benefit. Clinical trial registration information-Child and Adolescent Anxiety Disorders (CAMS); URL: http://clinicaltrials.gov. Unique identifier: NCT00052078.

They're Not Just "Little Adults": Developmental Considerations for Implementing Cognitive-Behavioral Therapy With Anxious Youth

Developmental factors direct optimal implementations of cognitive-behavioral therapy (GBT) protocols with children and adolescents. Although chronological age can approximate level of development, youthful clients benefit v^rhen clinicians carefully assess each childs cognitive, social, and emotional skills and adjust manualized treatments accordingly. Using several components of manualized GBT for anxiety in youth (i.e., affective education, cognitive restructuring, exposure tasks) as a framework, this article reviews empirical literature and provides practical suggestions for modifying these aspects of treatment to fit a childs level of development. Important issues such as engaging youth in treatment, and involving school personnel and parents in this process are also discussed. This article concludes with a call for

Trajectories of Change in Youth Anxiety during Cognitive Behavior Therapy

OBJECTIVE To evaluate changes in the trajectory of youth anxiety following the introduction of specific cognitive-behavior therapy (CBT) components: relaxation training, cognitive restructuring, and exposure tasks. METHOD Four hundred eighty-eight youths ages 7-17 years (50% female; 74% ≤ 12 years) were randomly assigned to receive either CBT, sertraline (SRT), their combination (COMB), or pill placebo (PBO) as part of their participation in the Child/Adolescent Anxiety Multimodal Study (CAMS). Youths in the CBT conditions were evaluated weekly by therapists using the Clinical Global Impression Scale-Severity (CGI-S; Guy, 1976) and the Childrens Global Assessment Scale (CGAS; Shaffer et al., 1983) and every 4 weeks by blind independent evaluators (IEs) using the Pediatric Anxiety Ratings Scale (PARS; RUPP Anxiety Study Group, 2002). Youths in SRT and PBO were included as controls. RESULTS Longitudinal discontinuity analyses indicated that the introduction of both cognitive restructuring (e.g., changing self-talk) and exposure tasks significantly accelerated the rate of progress on measures of symptom severity and global functioning moving forward in treatment; the introduction of relaxation training had limited impact. Counter to expectations, no strategy altered the rate of progress in the specific domain of anxiety that it was intended to target (i.e., somatic symptoms, anxious self-talk, avoidance behavior). CONCLUSIONS Findings support CBT theory and suggest that cognitive restructuring and exposure tasks each make substantial contributions to improvement in youth anxiety. Implications for future research are discussed. (PsycINFO Database Record

Defining Treatment Response and Remission in Child Anxiety: Signal Detection Analysis Using the Pediatric Anxiety Rating Scale

OBJECTIVE To determine optimal Pediatric Anxiety Rating Scale (PARS) percent reduction and raw score cut-offs for predicting treatment response and remission among children and adolescents with anxiety disorders. METHOD Data were from a subset of youth (N = 438; 7-17 years of age) who participated in the Child/Adolescent Anxiety Multimodal Study (CAMS), a multi-site, randomized controlled trial that examined the relative efficacy of cognitive-behavioral therapy (CBT; Coping Cat), medication (sertraline [SRT]), their combination, and pill placebo for the treatment of separation anxiety disorder, generalized anxiety disorder, and social phobia. The clinician-rated PARS was administered pre- and posttreatment (delivered over 12 weeks). Quality receiver operating characteristic methods assessed the performance of various PARS percent reductions and absolute cut-off scores in predicting treatment response and remission, as determined by posttreatment ratings on the Clinical Global Impression scales and the Anxiety Disorders Interview Schedule for DSM-IV. Corresponding change in impairment was evaluated using the Child Anxiety Impact Scale. RESULTS Reductions of 35% and 50% on the six-item PARS optimally predicted treatment response and remission, respectively. Post-treatment PARS raw scores of 8 to 10 optimally predicted remission. Anxiety improved as a function of PARS-defined treatment response and remission. CONCLUSIONS Results serve as guidelines for operationalizing treatment response and remission in future research and in making cross-study comparisons. These guidelines can facilitate translation of research findings into clinical practice.

Assessing Anxiety in Youth with the Multidimensional Anxiety Scale for Children.

The present study examined the psychometric properties, including discriminant validity and clinical utility, of the youth self-report and parent-report forms of the Multidimensional Anxiety Scale for Children (MASC) among youth with anxiety disorders. The sample included parents and youth (N = 488, 49.6% male) ages 7 to 17 who participated in the Child/Adolescent Anxiety Multimodal Study. Although the typical low agreement between parent and youth self-reports was found, the MASC evidenced good internal reliability across MASC subscales and informants. The main MASC subscales (i.e., Physical Symptoms, Harm Avoidance, Social Anxiety, and Separation/Panic) were examined. The Social Anxiety and Separation/Panic subscales were found to be significantly predictive of the presence and severity of social phobia and separation anxiety disorder, respectively. Using multiple informants improved the accuracy of prediction. The MASC subscales demonstrated good psychometric properties and clinical utilities in identifying youth with anxiety disorders.