An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis.

INTRODUCTION: Expert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. METHODS: We conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. RESULTS: Individual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. CONCLUSION: While the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

Kundalini Yoga Meditation Versus the Relaxation Response Meditation for Treating Adults With Obsessive-Compulsive Disorder: A Randomized Clinical Trial.

Background: Obsessive-compulsive disorder (OCD) is often a life-long disorder with high psychosocial impairment. Serotonin reuptake inhibitors (SRIs) are the only FDA approved drugs, and approximately 50% of patients are non-responders when using a criterion of 25% to 35% improvement with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). About 30% are non-responders to combined first-line therapies (SRIs and exposure and response prevention). Previous research (one open, one randomized clinical trial) has demonstrated that Kundalini Yoga (KY) meditation can lead to an improvement in symptoms of obsessive-compulsive severity. We expand here with a larger trial. Design: This trial compared two parallel run groups [KY vs. Relaxation Response meditation (RR)]. Patients were randomly allocated based on gender and Y-BOCS scores. They were told two different (unnamed) types of meditation would be compared, and informed if one showed greater benefits, the groups would merge for 12 months using the more effective intervention. Raters were blind in Phase One (0-4.5 months) to patient assignments, but not in Phase Two. Main Outcome Measures: Primary outcome variable, clinician-administered Y-BOCS. Secondary scales: Dimensional Yale-Brown Obsessive Compulsive Scale (clinician-administered), Profile of Mood Scales, Beck Anxiety Inventory, Beck Depression Inventory, Clinical Global Impression, Short Form 36 Health Survey. Results: Phase One: Baseline Y-BOCS scores: KY mean = 26.46 (SD 5.124; N = 24), RR mean = 26.79 (SD = 4.578; N = 24). An intent-to-treat analysis with the last observation carried forward for dropouts showed statistically greater improvement with KY compared to RR on the Y-BOCS, and statistically greater improvement on five of six secondary measures. For completers, the Y-BOCS showed 40.4% improvement for KY (N = 16), 17.9% for RR (N = 11); 31.3% in KY were judged to be in remission compared to 9.1% in RR. KY completers showed greater improvement on five of six secondary measures. At the end of Phase Two (12 months), patients, drawn from the initial groups, who elected to receive KY continued to show improvement in their Y-BOCS scores. Conclusion: KY shows promise as an add-on option for OCD patients unresponsive to first line therapies. Future studies will establish KY's relative efficacy compared to Exposure and Response Prevention and/or medications, and the most effective treatment schedule. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01833442.

Adaptive treatment strategies for children and adolescents with Obsessive-Compulsive Disorder: A sequential multiple assignment randomized trial.

OBJECTIVE: This sequential multiple assignment randomized trial (SMART) tested the effect of beginning treatment of childhood OCD with fluoxetine (FLX) or group cognitive-behavioral therapy (GCBT) accounting for treatment failures over time. METHODS: A two-stage, 28-week SMART was conducted with 83 children and adolescents with OCD. Participants were randomly allocated to GCBT or FLX for 14 weeks. Responders to the initial treatment remained in the same regimen for additional 14 weeks. Non-responders, defined by less than 50% reduction in baseline Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores, were re-randomized to either switch to or add the other treatment. Assessments were performed at baseline, 7, 14, 21, and 28 weeks. RESULTS: Among the 43 children randomized to FLX who completed the first stage, 15 (41.7%) responded to treatment and 21 non-responders were randomized to switch to (N = 9) or add GCBT (N = 12). Among the 40 children randomized to GCBT who completed the first stage, 18 (51.4%) responded to treatment and 17 non-responders were randomized to switch to (N = 9) or add FLX (N = 8). Primary analysis showed that significant improvement occurred in children initially treated with either FLX or GCBT. Each time point was statistically significant, showing a linear trend of symptom reduction. Effect sizes were large within (0.76-0.78) and small between (-0.05) groups. CONCLUSIONS: Fluoxetine and GCBT are similarly effective initial treatments for childhood OCD considering treatment failures over time. Consequently, provision of treatment for childhood OCD could be tailored according to the availability of local resources.

Acute and longer-term safety results from a pooled analysis of duloxetine studies for the treatment of children and adolescents with major depressive disorder.

OBJECTIVE: To assess acute and longer-term safety of duloxetine in the treatment of children and adolescents with major depressive disorder (MDD), a pooled analysis of data from two completed randomized, double-blind, multicenter, phase 3, placebo- and active-controlled trials was undertaken. In these studies, neither duloxetine (investigational drug) nor fluoxetine (active control) demonstrated a statistically significant improvement compared with placebo on the primary efficacy measure. METHODS: Patients ages 7-17 years with MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) received duloxetine (n=341), fluoxetine (n=234), or placebo (n=225) for 10 week acute and 26 week extended (duloxetine or fluoxetine only) treatments. Safety measures included treatment-emergent adverse events (TEAEs), the Columbia-Suicide Severity Rating Scale, vital signs, electrocardiograms, laboratory samples, and growth (height and weight) assessments. RESULTS: Significantly more patients discontinued because of adverse events during duloxetine (8.2%) treatment than during placebo (3.1%) treatment (p≤0.05). TEAEs in >10% of duloxetine-treated patients were headache and nausea. No completed suicides or deaths occurred. During acute treatment, 6.6% of duloxetine-, 8.0% of fluoxetine-, and 8.2% of placebo-treated patients had worsening suicidal ideation from baseline. Among patients initially randomized to duloxetine or fluoxetine who had suicidal ideation at study baseline, 81% of duloxetine- and 77% of fluoxetine-treated patients had improvements in suicidal ideation at end-point in the 36-week studies. Suicidal behavior occurred in two fluoxetine-treated patients and one placebo-treated patient during acute treatment, and in seven duloxetine-treated patients and one fluoxetine-treated patient during extended treatment. Duloxetine-treated patients had a mean pulse increase of ∼3 beats per minute, and mean blood pressure (both systolic and diastolic) increases of <2.0 mm Hg at week 36. Weight decrease (≥3.5%) during acute treatment occurred with statistically (p≤0.05) greater frequency for both the duloxetine (11.4%) and fluoxetine (11.5%) groups versus the placebo (5.5%) group; however, mean weight increase occurred for both duloxetine and fluoxetine groups during extended treatment. CONCLUSION: Results from this pooled analysis of two studies were consistent with the known safety and tolerability profile of duloxetine. Clinical Trial Registry Numbers: NCT00849901 and NCT00849693.

Child/Adolescent anxiety multimodal study: evaluating safety.

OBJECTIVE: To evaluate the frequency of adverse events (AEs) across 4 treatment conditions in the Child/Adolescent Anxiety Multimodal Study (CAMS), and to compare the frequency of AEs between children and adolescents. METHOD: Participants ages 7 to 17 years (mean = 10.7 years) meeting the DSM-IV criteria for 1 or more of the following disorders: separation anxiety disorder, generalized anxiety disorder, or social phobia were randomized (2:2:2:1) to cognitive-behavioral therapy (CBT, n = 139), sertraline (SRT, n = 133), a combination of both (COMB, n = 140), or pill placebo (PBO, n = 76). Data on AEs were collected via a standardized inquiry method plus a self-report Physical Symptom Checklist (PSC). RESULTS: There were no differences between the double-blinded conditions (SRT versus PBO) for total physical and psychiatric AEs or any individual physical or psychiatric AEs. The rates of total physical AEs were greater in the SRT-alone treatment condition when compared to CBT (p < .01) and COMB (p < .01). Moreover, those who received SRT alone reported higher rates of several physical AEs when compared to COMB and CBT. The rate of total psychiatric AEs was higher in children (≤12 years) across all arms (31.7% versus 23.1%, p < .05). Total PSC scores decreased over time, with no significant differences between treatment groups. CONCLUSION: The results support the tolerability/safety of selective serotonin reuptake inhibitor (SSRI) treatment for anxiety disorders even after adjusting for the number of reporting opportunities, leading to no differences in overall rates of AEs. Few differences occurred on specific items. Additional monitoring of psychiatric AEs is recommended in children (≤12 years). Clinical trial registration information-Child and Adolescent Anxiety Disorders (CAMS); http://clinicaltrials.gov; NCT00052078.

Anxiety Disorders in Caucasian and African American Children: A Comparison of Clinical Characteristics, Treatment Process Variables, and Treatment Outcomes.

This study examined racial differences in anxious youth using data from the Child/Adolescent Anxiety Multimodal Study (CAMS) [1]. Specifically, the study aims addressed whether African American (n = 44) versus Caucasian (n = 359) children varied on (1) baseline clinical characteristics, (2) treatment process variables, and (3) treatment outcomes. Participants were ages 7-17 and met DSM-IV-TR criteria for generalized anxiety disorder, social phobia, and/or separation anxiety disorder. Baseline data, as well as outcome data at 12 and 24 weeks, were obtained by independent evaluators. Weekly treatment process variables were collected by therapists. Results indicated no racial differences on baseline clinical characteristics. However, African American participants attended fewer psychotherapy and pharmacotherapy sessions, and were rated by therapists as less involved and compliant, in addition to showing lower mastery of CBT. Once these and other demographic factors were accounted for, race was not a significant predictor of response, remission, or relapse. Implications of these findings suggest African American and Caucasian youth are more similar than different with respect to the manifestations of anxiety and differences in outcomes are likely due to treatment barriers to session attendance and therapist engagement.

A double-blind efficacy and safety study of duloxetine fixed doses in children and adolescents with major depressive disorder.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of duloxetine fixed dose in the treatment of children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD). METHODS: Patients (n=463) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine 60 mg QD (n=108), duloxetine 30 mg QD (n=116), fluoxetine 20 mg QD (n=117, active control), or placebo (n=122). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. Total TEAEs and discontinuation for AEs were significantly (p<0.05) higher only for the duloxetine 60 mg group versus the placebo group during acute treatment. No clinically significant electrocardiogram (ECG) or laboratory abnormalities were observed, and no completed suicides or deaths occurred during the study. A total of 7 (6.7%) duloxetine 60 mg, 6 (5.2%) duloxetine 30 mg, 9 (8.0%) fluoxetine, and 11 (9.4%) placebo patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 13/16 (81%) duloxetine 60 mg, 16/17 (94%) duloxetine 30 mg, 11/16 (69%) fluoxetine, and 13/15 (87%) placebo had improvement in suicidal ideation at end-point during acute treatment. One fluoxetine, one placebo, and six duloxetine patients had treatment-emergent suicidal behavior during the 36 week study. CONCLUSIONS: Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number ( www.ClinicalTrials.gov ): NCT00849693.

A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of duloxetine flexible dose in children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD). METHODS: Patients (n=337) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine (60-120 mg once daily [QD], n=117), fluoxetine (20-40 mg QD, n=117), or placebo (n=103). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. There were no significant differences between the duloxetine or fluoxetine groups compared with placebo on serious AEs (SAEs), total TEAEs, or discontinuation for AE during acute treatment. There were no completed suicides or deaths, and no clinically significant electrocardiogram (ECG) abnormalities observed during the study. One fluoxetine and one duloxetine patient experienced alanine aminotransferase (ALT) three or more times the upper limit of normal, which resolved during the study. A total of 8 (7.1%) duloxetine patients, 7 (6.8%) placebo patients, and 9 (8.0%) fluoxetine patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 15/19 (79%) duloxetine, 19/19 (100%) placebo, and 16/19 (84%) fluoxetine had improvement in suicidal ideation at end-point during acute treatment. One duloxetine and two fluoxetine patients had treatment-emergent suicidal behavior during the 36 week study. CONCLUSION: Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number: NCT00849901.

Predictors and moderators of treatment response in childhood anxiety disorders: results from the CAMS trial.

OBJECTIVE: We sought to examine predictors and moderators of treatment outcomes among 488 youths ages 7-17 years (50% female; 74% ≤ 12 years) meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000) criteria for diagnoses of separation anxiety disorder, social phobia, or generalized anxiety disorder who were randomly assigned to receive either cognitive behavioral therapy (CBT), sertraline (SRT), their combination (COMB), or medication management with pill placebo (PBO) in the Child/Adolescent Anxiety Multimodal Study (CAMS). METHOD: Six classes of predictor and moderator variables (22 variables) were identified from the literature and examined using continuous (Pediatric Anxiety Ratings Scale; PARS) and categorical (Clinical Global Impression Scale-Improvement; CGI-I) outcome measures. RESULTS: Three baseline variables predicted better outcomes (independent of treatment condition) on the PARS, including low anxiety severity (as measured by parents and independent evaluators) and caregiver strain. No baseline variables were found to predict Week 12 responder status (CGI-I). Participants' principal diagnosis moderated treatment outcomes but only on the PARS. No baseline variables were found to moderate treatment outcomes on Week 12 responder status (CGI-I). DISCUSSION: Overall, anxious children responded favorably to CAMS treatments. However, having more severe and impairing anxiety, greater caregiver strain, and a principal diagnosis of social phobia were associated with less favorable outcomes. Clinical implications of these findings are discussed.

Benefits of child-focused anxiety treatments for parents and family functioning.

BACKGROUND: To examine (1) changes in parent (global psychological distress, trait anxiety) and family (dysfunction, burden) functioning following 12 weeks of child-focused anxiety treatment, and (2) whether changes in these parent and family factors were associated with child's treatment condition and response. METHODS: Participants were 488 youth ages 7-17 years (50% female; mean age 10.7 years) who met DSM-IV-TR criteria for social phobia, separation anxiety, and/or generalized anxiety disorder, and their parents. Youth were randomly assigned to 12 weeks of "Coping Cat" individual cognitive-behavioral therapy (CBT), medication management with sertraline (SRT), their combination (COMB), or medication management with pill placebo (PBO) within the multisite Child/Adolescent Anxiety Multimodal Study (CAMS). At pre- and posttreatment, parents completed measures of trait anxiety, psychological distress, family functioning, and burden of child illness; children completed a measure of family functioning. Blinded independent evaluators rated child's response to treatment using the Clinical Global Impression-Improvement Scale at posttreatment. RESULTS: Analyses of covariance revealed that parental psychological distress and trait anxiety, and parent-reported family dysfunction improved only for parents of children who were rated as treatment responders, and these changes were unrelated to treatment condition. Family burden and child-reported family dysfunction improved significantly from pre- to posttreatment regardless of treatment condition or response. CONCLUSIONS: Findings suggest that child-focused anxiety treatments, regardless of intervention condition, can result in improvements in nontargeted parent symptoms and family functioning particularly when children respond successfully to the treatment.

Therapist Factors and Outcomes in CBT for Anxiety in Youth.

This study examined the relationship between therapist factors and child outcomes in anxious youth who received cognitive-behavioral therapy (CBT) as part of the Child-Adolescent Anxiety Multimodal Study (CAMS). Of the 488 youth who participated in the CAMS project, 279 were randomly assigned to one of the CBT conditions (CBT only or CBT plus sertraline). Participants included youth (ages 7-17; M = 10.76) who met criteria for a principal anxiety disorder. Therapists included 38 cognitive-behavioral therapists. Therapist style, treatment integrity, and therapist experience were examined in relation to child outcome. Child outcome was measured via child, parent, and independent evaluator report. Therapists who were more collaborative and empathic, followed the treatment manual, and implemented it in a developmentally appropriate way had youth with better treatment outcomes. Therapist "coach" style was a significant predictor of child-reported outcome, with the collaborative "coach" style predicting fewer child-reported symptoms. Higher levels of therapist prior clinical experience and lower levels of prior anxiety-specific experience were significant predictors of better treatment outcome. Findings suggest that although all therapists used the same manual-guided treatment, therapist style, experience, and clinical skills were related to differences in child outcome. Clinical implications and recommendations for future research are discussed.

Are increased weight and appetite useful indicators of depression in children and adolescents?

During childhood and adolescence, physiological, psychological, and behavioral processes strongly promote weight gain and increased appetite while also inhibiting weight loss and decreased appetite. The Diagnostic and Statistical Manual-IV (DSM-IV) treats both weight-gain/increased-appetite and weight-loss/decreased-appetite as symptoms of major depression during these developmental periods, despite the fact that one complements typical development and the other opposes it. To disentangle the developmental versus pathological correlates of weight and appetite disturbance in younger age groups, the current study examined symptoms of depression in an aggregated sample of 2307 children and adolescents, 47.25% of whom met criteria for major depressive disorder. A multigroup, multidimensional item response theory model generated three key results. First, weight loss and decreased appetite loaded strongly onto a general depression dimension; in contrast, weight gain and increased appetite did not. Instead, weight gain and increased appetite loaded onto a separate dimension that did not correlate strongly with general depression. Second, inclusion or exclusion of weight gain and increased appetite affected neither the nature of the general depression dimension nor the fidelity of major depressive disorder diagnosis. Third, the general depression dimension and the weight-gain/increased-appetite dimension showed different patterns across age and gender. In child and adolescent populations, these results call into question the utility of weight gain and increased appetite as indicators of depression. This has serious implications for the diagnostic criteria of depression in children and adolescents. These findings inform a revision of the DSM, with implications for the diagnosis of depression in this age group and for research on depression.

Diagnostic efficiency of the child and parent versions of the Multidimensional Anxiety Scale for Children.

The objective of this study is to evaluate the psychometrics and clinical efficiency of the Multidimensional Anxiety Scale for Children (MASC), which measures physical symptoms, harm avoidance, social anxiety, and separation/panic. Using a sample of 190 treatment-seeking Norwegian youth (aged 7-13 years, M (age) = 10.3 years, 62.1% male), the internal stability and ability to predict to disorder were examined for child, mother, and father reports on the MASC. Moderate to strong internal reliability was exhibited across all MASC subscales. Parent-child agreement was low, but mother-father agreement was high. MASC scores successfully distinguished between children with and without anxiety disorders and identified youth with separation anxiety disorder and social phobia, but less accurately generalized anxiety disorders. The MASC has favorable psychometric properties and is a useful screening instrument for identifying youth with anxiety disorders.

An open-label safety and pharmacokinetics study of duloxetine in pediatric patients with major depression.

OBJECTIVE: This preliminary, 32-week study assessed the safety, tolerability, and pharmacokinetics of duloxetine in pediatric patients (aged 7-17 years) with major depressive disorder. METHODS: Patients received flexible duloxetine doses of 20-120 mg once daily, with dose changes made based on clinical improvement and tolerability. Pharmacokinetic samples were collected across all duloxetine doses, and data were analyzed using population modeling. Primary outcome measures included treatment-emergent adverse events (TEAEs), vital signs, and Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: Of the 72 enrolled patients, 48 (66.7%) completed acute treatment (18 weeks) and 42 (58.3%) completed extended treatment. Most patients (55/72; 76%) required doses ≥ 60 mg once daily to optimize efficacy based on investigator judgment and Clinical Global Impressions-Severity score. Body weight and age did not significantly affect duloxetine pharmacokinetic parameters. Typical duloxetine clearance in pediatric patients was ≈ 42%-60% higher than that in adults. Four patients (5.6%) discontinued due to TEAEs. Many (36/72, 50%) patients experienced potentially clinically significant (PCS) elevations in blood pressure, with most cases (21/36, 58%) being transient. As assessed via C-SSRS, one nonfatal suicidal attempt occurred, two patients (2.8%) experienced worsening of suicidal ideation, and among the 19 patients reporting suicidal ideation at baseline, 17 (90%) reported improvement in suicidal ideation. CONCLUSION: Results suggested that pediatric patients generally tolerated duloxetine doses of 30 to 120 mg once daily, although transient PCS elevations in blood pressure were observed in many patients. Pharmacokinetic results suggested that adjustment of total daily dose based on body weight or age is not warranted for pediatric patients and different total daily doses may not be warranted for pediatric patients relative to adults.

The evidence-based pharmacological treatment of paediatric ADHD.

Attention deficit hyperactivity disorder (ADHD) is common in children, adolescents, and adults, with extensive research establishing it as a valid neurobiological disorder. Without intervention, ADHD can result in significant impairment throughout the lifespan for the individuals it afflicts. Fortunately, multiple evidence-based options are available for the treatment of ADHD, including several efficacious pharmacotherapies. The role of medication, including stimulants as well as non-stimulants, is well-documented by an extensive body of literature. Although there may be less enthusiasm for behavioural and other psychosocial interventions as stand-alone treatments for moderate to severe ADHD, they are recommended as first-line treatment for ADHD management in preschool-aged children, for those patients with mild symptoms, and as an adjunct to medication in patients with comorbid disorders or suboptimal responses to pharmacotherapy. When planning treatment for individuals with ADHD, the potential risks associated with the available interventions must be carefully balanced against the risks of not treating, or not treating adequately. The treatment plan must also include ongoing re-assessment of the effectiveness of and the need for continued therapy. Recent practice parameters provide further specific guidance for the evidence-based assessment and treatment of children and adolescents with ADHD.

Maternal and child expressed emotion as predictors of treatment response in pediatric obsessive-compulsive disorder.

Expressed emotion (EE) is associated with symptoms and treatment outcome in various disorders. Few studies have examined EE in pediatric OCD and none of these has assessed the child's perspective. This study examined the relationship among maternal and child EE, child OCD severity, and OCD-related functioning pre- and post-treatment. At pre-treatment, mothers completed speech samples about the child with OCD and an unaffected sibling. Children with OCD completed speech samples about parents. There were low rates of high maternal EE (child with OCD: 16.1%; sibling: 2.6%) and high child EE about parents (mothers: 11.9%; fathers: 10.2%). High EE was primarily characterized by high criticism, not high overinvolvement. High maternal EE and child EE regarding fathers were associated with pre-treatment child OCD severity but not post-treatment severity. High child and maternal EE were predictive of post-treatment OCD-related functioning. EE may be an important child and maternal trait associated with pre-treatment OCD severity and generalization of treatment gains.

Cognitive behavior therapy augmentation of pharmacotherapy in pediatric obsessive-compulsive disorder: the Pediatric OCD Treatment Study II (POTS II) randomized controlled trial.

CONTEXT: The extant literature on the treatment of pediatric obsessive-compulsive disorder (OCD) indicates that partial response to serotonin reuptake inhibitors (SRIs) is the norm and that augmentation with short-term OCD-specific cognitive behavior therapy (CBT) may provide additional benefit. OBJECTIVE: To examine the effects of augmenting SRIs with CBT or a brief form of CBT, instructions in CBT delivered in the context of medication management. DESIGN, SETTING, AND PARTICIPANTS: A 12-week randomized controlled trial conducted at 3 academic medical centers between 2004 and 2009, involving 124 pediatric outpatients between the ages of 7 and 17 years with OCD as a primary diagnosis and a Children's Yale-Brown Obsessive Compulsive Scale score of 16 or higher despite an adequate SRI trial. INTERVENTIONS: Participants were randomly assigned to 1 of 3 treatment strategies that included 7 sessions over 12 weeks: 42 in the medication management only, 42 in the medication management plus instructions in CBT, and 42 in the medication management plus CBT; the last included 14 concurrent CBT sessions. MAIN OUTCOME MEASURES: Whether patients responded positively to treatment by improving their baseline obsessive-compulsive scale score by 30% or more and demonstrating a change in their continuous scores over 12 weeks. RESULTS: The medication management plus CBT strategy was superior to the other 2 strategies on all outcome measures. In the primary intention-to-treat analysis, 68.6% (95% CI, 53.9%-83.3%) in the plus CBT group were considered responders, which was significantly better than the 34.0% (95% CI, 18.0%-50.0%) in the plus instructions in CBT group, and 30.0% (95% CI, 14.9%-45.1%) in the medication management only group. The results were similar in pairwise comparisons with the plus CBT strategy being superior to the other 2 strategies (P < .01 for both). The plus instructions in CBT strategy was not statistically superior to medication management only (P = .72). The number needed-to-treat analysis with the plus CBT vs medication management only in order to see 1 additional patient at week 12, on average, was estimated as 3; for the plus CBT vs the plus instructions in CBT strategy, the number needed to treat was also estimated as 3; for the plus instructions in CBT vs medication management only the number needed to treat was estimated as 25. CONCLUSIONS: Among patients aged 7 to 17 years with OCD and partial response to SRI use, the addition of CBT to medication management compared with medication management alone resulted in a significantly greater response rate, whereas augmentation of medication management with the addition of instructions in CBT did not. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00074815.

An effectiveness study of a culturally enriched school-based CBT anxiety prevention program.

Anxiety disorders are prevalent in the school-aged population and are present across cultural groups. Scant research exists on culturally relevant prevention and intervention programs for mental health problems in the Aboriginal populations. An established cognitive behavioral program, FRIENDS for Life, was enriched to include content that was culturally relevant to Aboriginal students. Students (N = 533), including 192 students of Aboriginal background, participated in the cluster randomized control study. Data were collected three times over 1 year. A series of multilevel models were conducted to examine the effect of the culturally enriched FRIENDS program on anxiety. These analyses revealed that the FRIENDS program did not effectively reduce anxiety for the total sample or for Aboriginal children specifically. However, all students, regardless of intervention condition, Aboriginal status, or gender, reported a consistent decrease in feelings of anxiety over the 6-month study period.

Developments in pediatric psychopharmacology: focus on stimulants, antidepressants, and antipsychotics.

Most major psychiatric disorders have an onset in childhood or adolescence in a sizeable proportion of patients, and earlier onset disorders often have a severe and chronic course that can seriously disrupt sensitive developmental periods, with lifelong adverse consequences. Accordingly, psychopharmacologic treatments have been increasingly utilized in severely ill youth. However, the increased use of psychopharmacologic treatments in pediatric patients has also raised concerns regarding a potential overdiagnosis and overtreatment of youth, without adequate data regarding the pediatric efficacy and safety of psychotropic agents. Over the past decade, a remarkable number of pediatric randomized controlled trials have been completed, especially with psychostimulants, antidepressants, and antipsychotics. For these frequently used agents, effect sizes against placebo have typically been at least moderate, with most numbers-needed-to-treat well below 10 for response, indicating clinical significance as well. Nevertheless, data also point to a greater and/or different profile of susceptibility to adverse effects in pediatric compared to adult patients, as well as to a role for nonpharmacologic treatments, given alone or combined with pharmacotherapy, for many of the youth. Taken together, these results highlight the need for a careful assessment of the risk-benefit relationship of psychopharmacologic treatments in patients who cannot be managed sufficiently with nonpharmacologic interventions and for routine, proactive adverse effect monitoring and management. Although considerable progress has been made, there is still enormous need for additional data and funding of pediatric psychopharmacology trials. It is hoped that the field will acquire the necessary resources to propel pediatric clinical psychopharmacology to new levels of insight by linking it with, but not replacing it by, pharmacoepidemiologic and biomarker approaches and advances.