Dara Sakolsky

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.

Naturalistic Follow-up of Youths Treated for Pediatric Anxiety Disorders

IMPORTANCE Pediatric anxiety disorders are highly prevalent and impairing and are considered gateway disorders in that they predict adult psychiatric problems. Although they can be effectively treated in the short term, data are limited on the long-term outcomes in treated children and adolescents, particularly those treated with medication. OBJECTIVE To determine whether acute clinical improvement and treatment type (i.e., cognitive behavioral therapy, medication, or their combination) predicted remission of anxiety and improvement in global functioning at a mean of 6 years after randomization and to examine predictors of outcomes at follow-up. DESIGN, SETTING, AND PARTICIPANTS This naturalistic follow-up study, as part of the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS), was conducted at 6 academic sites in the United States and included 288 youths (age range, 11-26 years; mean age, 17 years). Youths were randomized to 1 of 4 interventions (cognitive behavioral therapy, medication, combination, or pill placebo) in the Child/Adolescent Anxiety Multimodal Study (CAMS) and were evaluated a mean of 6 years after randomization. Participants in this study constituted 59.0% of the original CAMS sample. EXPOSURES Participants were assessed by independent evaluators using a semistructured diagnostic interview to determine the presence of anxiety disorders, the severity of anxiety, and global functioning. Participants and their parents completed questionnaires about mental health symptoms, family functioning, life events, and mental health service use. MAIN OUTCOMES AND MEASURES Remission, defined as the absence of all study entry anxiety disorders. RESULTS Almost half of the sample (46.5%) were in remission a mean of 6 years after randomization. Responders to acute treatment were significantly more likely to be in remission (odds ratio, 1.83; 95% CI, 1.08-3.09) and had less severe anxiety symptoms and higher functioning; the assigned treatment arm was unrelated to outcomes. Several predictors of remission and functioning were identified. CONCLUSIONS AND RELEVANCE Youths rated as responders during the acute treatment phase of CAMS were more likely to be in remission a mean of 6 years after randomization, although the effect size was small. Relapse occurred in almost half (48%) of acute responders, suggesting the need for more intensive or continued treatment for a sizable proportion of youths with anxiety disorders. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00052078.

Collaborative Care Outcomes for Pediatric Behavioral Health Problems: A Cluster Randomized Trial

OBJECTIVE: To assess the efficacy of collaborative care for behavior problems, attention-deficit/hyperactivity disorder (ADHD), and anxiety in pediatric primary care (Doctor Office Collaborative Care; DOCC). METHODS: Children and their caregivers participated from 8 pediatric practices that were cluster randomized to DOCC (n = 160) or enhanced usual care (EUC; n = 161). In DOCC, a care manager delivered a personalized, evidence-based intervention. EUC patients received psychoeducation and a facilitated specialty care referral. Care processes measures were collected after the 6-month intervention period. Family outcome measures included the Vanderbilt ADHD Diagnostic Parent Rating Scale, Parenting Stress Index-Short Form, Individualized Goal Attainment Ratings, and Clinical Global Impression-Improvement Scale. Most measures were collected at baseline, and 6-, 12-, and 18-month assessments. Provider outcome measures examined perceived treatment change, efficacy, and obstacles, and practice climate. RESULTS: DOCC (versus EUC) was associated with higher rates of treatment initiation (99.4% vs 54.2%; P < .001) and completion (76.6% vs 11.6%, P < .001), improvement in behavior problems, hyperactivity, and internalizing problems (P < .05 to .01), and parental stress (P < .05–.001), remission in behavior and internalizing problems (P < .01, .05), goal improvement (P < .05 to .001), treatment response (P < .05), and consumer satisfaction (P < .05). DOCC pediatricians reported greater perceived practice change, efficacy, and skill use to treat ADHD (P < .05 to .01). CONCLUSIONS: Implementing a collaborative care intervention for behavior problems in community pediatric practices is feasible and broadly effective, supporting the utility of integrated behavioral health care services.

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.

Psychopharmacologic Treatment of Children and Adolescents with Anxiety Disorders

Over the last decade, psychopharmacologic treatments for pediatric anxiety disorders have been developed and increasingly subjected to randomized, controlled trials. The authors summarize the data concerning the use of tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), atypical anxiolytics, and benzodiazepines. The extant data suggest that SSRIs--both as monotherapy and when combined with psychotherapy--are effective in the treatment of pediatric anxiety disorders. In addition, some TCAs and SNRIs are effective. However, randomized controlled trials do not suggest efficacy for benzodiazepines or the atypical anxiolytic, buspirone, for children and adolescents with anxiety disorders.

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

Pharmacokinetically and Clinician-Determined Adherence to an Antidepressant Regimen and Clinical Outcome in the TORDIA Trial

OBJECTIVE Nonadherence to antidepressant treatment may contribute to poor outcome and to suicidal adverse events in adolescent depression. We examine the relationship between adherence and both clinical response and suicidal events in participants in the Treatment of Resistant Depression in Adolescents (TORDIA) study. METHOD The relationship between adherence to medication and clinical outcome was assessed in 190 treatment-resistant depressed adolescents who were randomized to one of four cells: switch to another selective serotonin reuptake inhibitor (SSRI), switch to venlafaxine, or either of these two medication switches plus cognitive behavioral therapy. Plasma levels of antidepressant drug and metabolites were determined after 6 and 12 weeks of treatment. A twofold or greater variation in the dose-adjusted concentration of drug plus metabolites (level/dose ratio [LDR]) was defined as nonadherence. Nonadherence was also determined by clinician pill counts (CPC) of the proportion of prescribed pills that were unused and was defined as having greater than 30% of the prescribed pills remaining. RESULTS LDR and CPC showed low concordance. LDR was unrelated to clinical response. CPC adherence was related to a higher response rate overall (adherent, 63.0% versus nonadherent, 47.2%, p = .03). Approximately half (50.8%) of the sample surveyed showed evidence of nonadherence by CPC. Neither measure of adherence was related to the occurrence of suicidal events or to the pace of decline in suicidal ideation. CONCLUSIONS Clinician pill counts may be a relevant measure of adherence that is related to outcome under formal clinical trial conditions in depressed adolescents. Nonadherence appears to be a common and significant source of treatment nonresponse. Clinical Trial Registration Information-Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://www.clinicaltrials.gov; NCT00018902.

Psychosocial functioning in offspring of parents with bipolar disorder

BACKGROUND Offspring of parents with bipolar disorder are at increased risk for a range of psychopathology, including bipolar disorder. It is not clear if they also have impairments in their psychosocial functioning. METHODS We compared the psychosocial functioning of three groups of children enrolled in the Pittsburgh Bipolar Offspring Study (BIOS): offspring of probands with bipolar disorder (n=388), offspring of probands with other types of psychopathology (n=132), and offspring of healthy probands (n=118). Psychosocial functioning was assessed at study intake using the schedule of the Adolescent Longitudinal Interval Follow-Up Evaluation (A-LIFE), the Child Behavior Check List (CBCL) and the Childrens Global Assessment Scale (CGAS). RESULTS Offspring of probands with bipolar disorder exhibited impairments in various aspects of psychosocial functioning. On all measures, they had worse functioning in comparison with offspring of healthy probands. Offspring of probands with bipolar disorder generally exhibited more impairment than offspring of probands with nonbipolar psychopathology. After adjusting for proband parent functioning and the childs Axis I psychopathology, functioning of offspring of probands with bipolar disorder was similar to that of offspring of healthy probands. LIMITATIONS Data are cross-sectional and therefore do not allow for causal conclusions about the association between parental psychopathology, child psychopathology and offspring psychosocial functioning. CONCLUSIONS Offspring of parents with bipolar disorder exhibit impairments in psychosocial functioning which appear largely attributable to proband parent functional impairment and the childs own psychopathology. As such, interventions to improve parental functioning, as well as early interventions to treat the childs psychopathology may help reduce the risk for long-term functional impairment in offspring.

Dimensional psychopathology in offspring of parents with bipolar disorder.

Diler RS, Birmaher B, Axelson D, Obreja M, Monk K, Hickey MB, Goldstein B, Goldstein T, Sakolsky D, Iyengar S, Brent D, Kupfer D. Dimensional psychopathology in offspring of parents with bipolar disorder. Bipolar Disord 2011: 13: 670–678.