Drug overdose risk with benzodiazepine treatment in young adults: Comparative analysis in privately and publicly insured individuals.

BACKGROUND AND AIMS: Benzodiazepines (BZDs) carry a risk for drug overdose and are prescribed alone or simultaneously with selective-serotonin reuptake inhibitors (SSRIs) for the treatment of anxiety and depression in young adults. We aimed to measure risks of drug overdose following BZD treatment initiation, and simultaneous BZD and SSRI initiation, compared with SSRI treatment alone in young adults with depression or anxiety. DESIGN, SETTING, PARTICIPANTS: The cohort study used administrative databases covering privately (MarketScan, 1/1/2009-12/31/2018) and publicly (Medicaid, 1/1/2015-12/31/2016) insured young adults (18-29 years) in the United States. Those with depression or anxiety diagnoses newly initiating BZD or SSRI treatment (without BZD or SSRI prescriptions in prior year) were included. Simultaneous "BZD + SSRI" initiation was defined as starting BZD and SSRI treatment on the same day. The cohorts included 604 664 privately insured young adults (BZD = 22%, BZD + SSRI = 10%, SSRI = 68%) and 110 493 publicly insured young adults (BZD = 23%, BZD + SSRI = 5%, SSRI = 72%). MEASUREMENTS: Incident medically treated drug overdose events were identified from emergency department and inpatient encounters (ICD poisoning codes) within 6 months of treatment initiation. Crude and propensity-score adjusted cumulative incidence and hazard ratios (HR) were estimated. Sub-analyses evaluated drug overdose intent. FINDINGS: Adjusted HRs of drug overdose for BZD vs. SSRI treatment was 1.36 (95% confidence interval [CI]:1.23-1.51) in privately and 1.59 (95%CI:1.37-1.83) in publicly insured young adults. The adjusted HRs of drug overdose for BZD + SSRI treatment vs. SSRI treatment were 1.99 (95%CI:1.77-2.25) in privately and 1.98 (95%CI:1.47-2.68) in publicly insured young adults. CONCLUSIONS: Among young adults in the United States, initiating benzodiazepine treatment for anxiety and depression, alone or simultaneously with selective-serotonin reuptake inhibitors (SSRI), appears to have an increased risk of medically treated drug overdose compared with SSRI treatment alone. These associations were observed in publicly and privately insured individuals.

Subcortical shape in pediatric and adult obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) implicates alterations in cortico-striato-thalamo-cortical and fronto-limbic circuits. Building on prior structural findings, this is the largest study to date examining subcortical surface morphometry in OCD. METHODS: Structural magnetic resonance imaging data were collected from 200 participants across development (5-55 years): 28 youth and 75 adults with OCD and 27 psychiatrically healthy youth and 70 adults. General linear models were used to assess group differences and group-by-age interactions on subcortical shape (FSL FIRST). RESULTS: Compared to healthy participants, those with OCD exhibited surface expansions on the right nucleus accumbens and inward left amygdala deformations, which were associated with greater OCD symptom severity ([Children's] Yale-Brown Obsessive-Compulsive Scale). Group-by-age interactions indicated that accumbens group differences were driven by younger participants and that right pallidum shape was associated inversely with age in healthy participants, but not in participants with OCD. No differences in the shape of other subcortical regions or in volumes (FreeSurfer) were detected in supplementary analyses. CONCLUSIONS: This study is the largest to date examining subcortical shape in OCD and the first to do so across the developmental spectrum. NAcc and amygdala shape deformation builds on extant neuroimaging findings and suggests subtle, subregional alterations beyond volumetric findings. Results shed light on morphometric alterations in OCD, informing current pathophysiological models.

Simultaneous Benzodiazepine and SSRI Initiation in Young People With Anxiety Disorders.

Objective: There are potential risks and benefits of combining benzodiazepine (BZD) and selective serotonin reuptake inhibitor (SSRI) therapy at anxiety disorder treatment onset. We investigated how often adolescents and young adults with anxiety disorders simultaneously initiate BZD treatment with SSRI treatment and examined whether SSRI treatment duration varies by simultaneous BZD initiation.Methods: In a United States commercial claims database (January 2008-December 2016), we identified adolescents (10-17 years) and young adults (18-24 years) with ICD-9-CM/ICD-10-CM anxiety disorder diagnoses initiating SSRI treatment, without past-year SSRI and BZD treatment. We defined simultaneous initiation as filling a new BZD prescription on the date of SSRI initiation. We estimated time to SSRI treatment discontinuation and used stabilized inverse probability of treatment weighting for adjusted estimates.Results: The study included 94,399 adolescents and 130,971 young adults initiating SSRI treatment with an anxiety disorder. Four percent of adolescents and 17% of young adults simultaneously initiated BZD treatment, varying by age, anxiety disorder, comorbidities, health care utilization, and provider type. Simultaneous BZD initiation among SSRI initiators declined from 2008 to 2016. SSRI treatment duration was similar in initiators of simultaneous therapy vs SSRI monotherapy: ≥ 6 months in adolescents (55% vs 56%, respectively) and in young adults (39% vs 40%). Nine percent of simultaneous initiators continued BZDs for ≥ 6 months.Conclusions: Simultaneous initiation of BZD and SSRI treatment is relatively common in young adults with anxiety disorders and was not associated with longer SSRI persistence. Given risks of BZD treatment, potential benefits and risks of adding a BZD at SSRI treatment initiation must be carefully weighed.

Altered fronto-amygdalar functional connectivity predicts response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder.

BACKGROUND: Based on findings from adults with obsessive-compulsive disorder (OCD), this study examined alterations in resting-state functional connectivity (rs-fc) between the basolateral amygdala (BLA) and the ventromedial prefrontal cortex (vmPFC) in children and adolescents with OCD. We also assessed whether such BLA-vmPFC connectivity changed with or predicted response to exposure and response prevention (E/RP), the first-line treatment for pediatric OCD, given the involvement of these regions in fear processing, regulation, and extinction learning-a probable mechanism of action of E/RP. METHODS: Resting state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naïve pediatric patients with OCD (12.8 ± 2.9 years) and 23 age- and sex-matched healthy controls (HCs; 11.0 ± 3.3 years). Patients completed a 12-16-week E/RP intervention for OCD. Participants were rescanned after the 12-16-week period. ANCOVAs tested group differences in baseline rs-fc. Cross-lagged panel models examined relationships between BLA-vmPFC rs-fc and OCD symptoms pre- and posttreatment. All tests were adjusted for participants' age, sex, and head motion. RESULTS: Right BLA-vmPFC rs-fc was significantly reduced (more negative) in patients with OCD relative to HCs at baseline, and increased following treatment. In patients, more positive (less negative) right BLA-vmPFC rs-fc pretreatment predicted greater OCD symptoms reduction posttreatment. Changes in BLA-vmPFC rs-fc was unassociated with change in OCD symptoms pre- to posttreatment. CONCLUSIONS: These results provide further evidence of the BLA-vmPFC pathway as a potential target for novel treatments or prevention strategies aimed at facilitating adaptive learning and fear extinction in children with OCD or subclinical OCD symptoms.

Specialty knowledge and competency standards for pharmacotherapy for pediatric obsessive-compulsive disorder.

Evidence based treatments for pediatric Obsessive-Compulsive Disorder (OCD) are delivered with varying levels of expertise. This paper is part of the phase two series by the International OCD Accreditation Task Force (ATF) to advance a standardized high level of care globally. This paper presents specific knowledge and competencies recommended for specialized practice for pediatric psychopharmacologists working with OCD, developed by an international group of clinicians with extensive expertise in assessment and treatment of OCD. Tabulated knowledge and competency standards are operationalized as clinician abilities with specification of evidence for each standard. The distinction between current practice guidelines and ATF standards is discussed. Drug treatment has a solid evidence base. However, it should not be applied isolated, but informed by broad competence in general child and adolescent psychiatry and pediatrics. Other treatment relevant areas such as specialty CBT, family functioning, developmental issues, and neurobiology require consideration. Drug treatment includes several phases with varying degrees of evidence: Starting up medication, titration to maximum tolerated dose, maintenance, termination, and relapse prevention. In complex cases, pharmacotherapy with weak evidence may be needed to target symptoms and/or co-morbidity. The ATF knowledge and competency standards presented will be reviewed and updated commensurate with research.

Correction: Altered network connectivity predicts response to cognitive-behavioral therapy in pediatric obsessive-compulsive disorder.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Altered network connectivity predicts response to cognitive-behavioral therapy in pediatric obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is commonly associated with alterations in cortico-striato-thalamo-cortical brain networks. Yet, recent investigations of large-scale brain networks suggest that more diffuse alterations in brain connectivity may underlie its pathophysiology. Few studies have assessed functional connectivity within or between networks across the whole brain in pediatric OCD or how patterns of connectivity associate with treatment response. Resting-state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naive children and adolescents with OCD (12.8 ± 2.9 years) and 23 matched healthy control (HC) participants (11.0 ± 3.3 years) before participants with OCD completed a course of cognitive-behavioral therapy (CBT). Participants were re-scanned after 12-16 weeks. Whole-brain connectomic analyses were conducted to assess baseline group differences and group-by-time interactions, corrected for multiple comparisons. Relationships between functional connectivity and OCD symptoms pre- and post-CBT were examined using longitudinal cross-lagged panel modeling. Reduced connectivity in OCD relative to HC participants was detected between default mode and task-positive network regions. Greater (less altered) connectivity between left angular gyrus and left frontal pole predicted better response to CBT in the OCD group. Altered connectivity between task-positive and task-negative networks in pediatric OCD may contribute to the impaired control over intrusive thoughts early in the illness. This is the first study to show that altered connectivity between large-scale network regions may predict response to CBT in pediatric OCD, highlighting the clinical relevance of these networks as potential circuit-based targets for the development of novel treatments.

Structural neural markers of response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective, first-line treatment for pediatric obsessive-compulsive disorder (OCD). While neural predictors of treatment outcomes have been identified in adults with OCD, robust predictors are lacking for pediatric patients. Herein, we sought to identify brain structural markers of CBT response in youth with OCD. METHODS: Twenty-eight children/adolescents with OCD and 27 matched healthy participants (7- to 18-year-olds, M = 11.71 years, SD = 3.29) completed high-resolution structural and diffusion MRI (all unmedicated at time of scanning). Patients with OCD then completed 12-16 sessions of CBT. Subcortical volume and cortical thickness were estimated using FreeSurfer. Structural connectivity (streamline counts) was estimated using MRtrix. RESULTS: Thinner cortex in nine frontoparietal regions significantly predicted improvement in Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) scores (all ts > 3.4, FDR-corrected ps < .05). These included middle and superior frontal, angular, lingual, precentral, superior temporal, and supramarginal gyri (SMG). Vertex-wise analyses confirmed a significant left SMG cluster, showing large effect size (Cohen's d = 1.42) with 72.22% specificity and 90.00% sensitivity in predicting CBT response. Ten structural connections between cingulo-opercular regions exhibited fewer streamline counts in OCD (all ts > 3.12, Cohen's ds > 0.92) compared with healthy participants. These connections predicted post-treatment CY-BOCS scores, beyond pretreatment severity and demographics, though not above and beyond cortical thickness. CONCLUSIONS: The current study identified group differences in structural connectivity (reduced among cingulo-opercular regions) and cortical thickness predictors of CBT response (thinner frontoparietal cortices) in unmedicated children/adolescents with OCD. These data suggest, for the first time, that cortical and white matter features of task control circuits may be useful in identifying which pediatric patients respond best to individual CBT.

The Effects of Youth Anxiety Treatment on School Impairment: Differential Outcomes Across CBT, Sertraline, and their Combination.

Youth anxiety disorders are highly prevalent and are associated with considerable school impairment. Despite the identification of well-supported strategies for treating youth anxiety, research has yet to evaluate the differential effects of these treatments on anxiety-related school impairment. The present study leveraged data from the Child/Adolescent Anxiety Multimodal Study to examine differential treatment effects of CBT, sertraline, and their combination (COMB), relative to placebo (PBO), on anxiety-related school impairment among youth (N = 488). Latent growth modeling revealed that all three active treatments demonstrated superiority over PBO in reducing anxiety-related school impairment over time, with COMB showing the most robust effects. According to parent report, medication strategies may have stronger effects on anxiety-related school impairment among males than among females. Results were discrepant across parents and youth. Findings are discussed in terms of clinical implications for anxious youth and the need for continued research to examine treatment effects on anxiety-related school impairment.

Primary Care: Meeting the Mental Health Care Needs of Adolescents With Depression.

There is considerable evidence demonstrating the negative impact adolescent depression has on youth outcomes, such as poor school performance, social isolation, comorbid substance abuse, lack of employment, and, most concerning, the development of suicidal behaviors.1 Currently, the health system cannot meet the needs of youths with depression due to lack of access, shortage of trained clinicians, and inability to consistently deliver evidence-based care, especially in low-resource communities.2 To address this problem, we are turning to other health practitioners, specifically our primary care colleagues, to help provide effective care for adolescent depression and other mental health conditions.

Secondary Outcomes From the Child/Adolescent Anxiety Multimodal Study: Implications for Clinical Practice.

BACKGROUND: Controlled evaluations comparing medication, cognitive-behavioral therapy (CBT), and their combination in the treatment of youth anxiety have predominantly focused on global ratings by independent evaluators. Such ratings are resource-intensive, may be of limited generalizability, and do not directly inform our understanding of treatment responses from the perspective of treated families. We examined outcomes from the perspective of treated youth and parents in the Child/Adolescent Anxiety Multimodal Study (CAMS). METHODS: Participants (N=488; ages 7-17 years) who had a primary diagnosis of separation, social, and/or generalized anxiety disorder were randomly assigned to a treatment condition in the CAMS trial. Linear mixed-effects and ANCOVA models examined parent- and youth-reported anxiety symptoms, impact of anxiety, broader internalizing and externalizing psychopathology, depressive symptoms, and family burden throughout the 12-week acute treatment phase and 6-month follow-up. RESULTS: At week 12, combination treatment showed superiority over placebo, sertraline, and CBT with regard to parent-reported youth anxiety symptoms, and sertraline and CBT as monotherapies showed superiority over placebo with regard to parent-reported youth anxiety. Combination therapy and sertraline also showed week 12 superiority over placebo with regard to parent-reported internalizing psychopathology, and superiority over placebo and CBT with regard to parent-reported impact of anxiety, family burden, and youth depressive symptoms. By week 36, parent reports of many youth outcomes were comparable across active conditions. Youth measures tracked parent measures on many outcomes. CONCLUSIONS: Findings were drawn on brief, readily available questionnaires that in conjunction with clinician measures can inform patient-centered care and collaborative decision-making.Trial Registry Name: Child and Adolescent Anxiety Disorders (CAMS)Registry identification number: NCT00052078Registry URL: https://www.clinicaltrials.gov/ct2/show/NCT00052078.

Treating Pediatric Anxiety: Initial Use of SSRIs and Other Antianxiety Prescription Medications.

OBJECTIVE: Multiple pharmacotherapies for treating anxiety disorders exist, including selective serotonin reuptake inhibitors (SSRIs), the recommended first-line pharmacotherapy for pediatric anxiety. We sought to describe initial antianxiety medication use in children and estimate how long antianxiety medications were continued. METHODS: In a large commercial claims database, we identified children (3-17 years) initiating prescription antianxiety medication from 2004 to 2014 with a recent anxiety diagnosis (ICD-9-CM = 293.84, 300.0x, 300.2x, 300.3x, 309.21, 309.81, 313.23). We estimated the proportion of children initiating each medication class across the study period and used multivariable regression to evaluate factors associated with initiation with an SSRI. We evaluated treatment length for each initial medication class. RESULTS: Of 84,500 children initiating antianxiety medication, 70% initiated with an SSRI (63% [95% CI, 62%-63%] SSRI alone, 7% [95% CI, 7%-7%] SSRI + another antianxiety medication). Non-SSRI medications initiated included benzodiazepines (8%), non-SSRI antidepressants (7%), hydroxyzine (4%), and atypical antipsychotics (3%). Anxiety disorder, age, provider type, and comorbid diagnoses were associated with initial medication class. The proportion of children refilling their initial medication ranged from 19% (95% CI, 18%-20%) of hydroxyzine initiators and 25% (95% CI, 24%-26%) of benzodiazepine initiators to 81% (95% CI, 80%-81%) of SSRI initiators. Over half (55%, 95% CI, 55%-56%) of SSRI initiators continued SSRI treatment for 6 months. CONCLUSIONS: SSRIs are the most commonly used first-line medication for pediatric anxiety disorders, with about half of SSRI initiators continuing treatment for 6 months. Still, a third began therapy on a non-SSRI medication, for which there is limited evidence of effectiveness for pediatric anxiety, and a notable proportion of children initiated with 2 antianxiety medication classes.

Placebo Response in Pediatric Anxiety Disorders: Results from the Child/Adolescent Anxiety Multimodal Study.

OBJECTIVES: The aim of this study is to identify predictors of pill placebo response and to characterize the temporal course of pill placebo response in anxious youth. METHODS: Data from placebo-treated patients (N = 76) in the Child/Adolescent Anxiety Multimodal Study (CAMS), a multisite, randomized controlled trial that examined the efficacy of cognitive-behavioral therapy, sertraline, their combination, and placebo for the treatment of separation, generalized, and social anxiety disorders, were evaluated. Multiple linear regression models identified features associated with placebo response and models were confirmed with leave-one-out cross-validation. The likelihood of improvement in patients receiving pill placebo-over time-relative to improvement associated with active treatment was determined using probabilistic Bayesian analyses. RESULTS: Based on a categorical definition of response (Clinical Global Impressions-Improvement Scale score ≤2), nonresponders (n = 48), and pill placebo responders (n = 18) did not differ in age (p = 0.217), sex (p = 0.980), race (p = 0.743), or primary diagnosis (all ps > 0.659). In terms of change in anxiety symptoms, separation anxiety disorder and treatment expectation were associated with the degree of pill placebo response. Greater probability of placebo-related anxiety symptom improvement was observed early in the course of treatment (baseline to week 4, p < 0.0001). No significant change in the probability of placebo-related improvement was observed after week 4 (weeks 4-8, p = 0.07; weeks 8-12, p = 0.85), whereas the probability of improvement, in general, significantly increased week over week with active treatment. CONCLUSIONS: Pill placebo-related improvement occurs early in the course of treatment and both clinical factors and expectation predict this improvement. Additionally, probabilistic approaches may refine our understanding and prediction of pill placebo response.

Extended Release Guanfacine in Pediatric Anxiety Disorders: A Pilot, Randomized, Placebo-Controlled Trial.

OBJECTIVE: This is a feasibility study evaluating the safety, tolerability, and potential anxiolytic efficacy of the α2 agonist guanfacine extended-release (GXR) in children and adolescents with generalized anxiety disorder (GAD), separation anxiety disorder (SAD), or social phobia/social anxiety disorder. METHODS: Youth aged 6-17 years with a primary diagnosis of GAD, SAD, and/or social anxiety disorder were treated with flexibly dosed GXR (1-6 mg daily, n = 62) or placebo (n = 21) for 12 weeks. The primary aim of this study was to determine the safety and tolerability of GXR in youth with anxiety disorders, which involved the analysis of treatment-emergent adverse events (TEAEs), the emergence of suicidal ideation and behaviors, vital signs, and electrocardiographic/laboratory parameters. Exploratory efficacy measures included dimensional anxiety scales (Pediatric Anxiety Rating Scale [PARS] and Screen for Child Anxiety Related Emotional Disorders [SCARED]), as well as the Clinical Global Impression-Improvement (CGI-I) scale. As this was an exploratory study, no inferential statistical analyses were performed. RESULTS: GXR was safe and well tolerated. Treatment-related mean ± standard deviation changes in heart rate (GXR: 1.8 ± 12 beats per minute [bpm] decrease; placebo: 0.5 ± 11 bpm decrease), systolic blood pressure (GXR: 2.3 ± 11 mm Hg decrease; placebo: 1.7 ± 11 mm Hg decrease), or diastolic blood pressure (GXR: 1.3 ± 9 mm Hg decrease; placebo: 0.9 ± 7 mm Hg increase) were similar between treatment groups. TEAEs, including headache, somnolence/fatigue, abdominal pain, and dizziness, were consistent with the known safety profile of GXR. No differences were observed between treatment groups for PARS and SCARED scores, although at endpoint, a higher proportion of subjects receiving GXR versus placebo demonstrated CGI-I scores ≤2 (54.2% vs. 31.6%), as rated by the clinician investigator. CONCLUSIONS: GXR was well tolerated in pediatric subjects with GAD, SAD, and/or social anxiety disorder. ClinicalTrials.gov Identifier: NCT01470469.

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.

Efficacy and tolerability of antidepressants in pediatric anxiety disorders: a systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials have demonstrated that antidepressants are efficacious in the treatment of anxiety disorders in youth. However, there are no recent, systematic analyses of the efficacy, safety, or tolerability of these medications in pediatric anxiety disorders. METHODS: A systematic review and meta-analysis of prospective, randomized, parallel-group, controlled trials of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SSNRIs) in pediatric patients with non-obsessive compulsive disorder (OCD) anxiety disorders was undertaken using a search of PubMed/Medline (1966-2014). The meta-analysis utilized random-effects models to evaluate change in the Pediatric Anxiety Rating Scale or similar anxiety scale, suicidality, and adverse events. Additionally, pharmacologic variables were explored with regard to effect size, although no correction for multiple comparisons was made with regard to these relationships. RESULTS: Nine trials involving 1,673 patients and six medications were included. All SSRI/SSNRIs evaluated demonstrated efficacy, and the meta-analytic estimate of effect was of moderate magnitude (Cohen's d = 0.62, confidence interval [CI]: 0.34-0.89, P = .009) and there was evidence of modest heterogeneity (I(2) = 0.29, P = .103). Activation trended toward being more likely with antidepressant treatment (OR: 1.86, CI: 0.98-3.53, P = .054), but no increased risk was observed for nausea/abdominal symptoms (P = .262), discontinuation as a result of an adverse event (P = .132), or suicidality (OR: 1.3, CI: 0.53-3.2, P = .514). Finally, the effect size correlated with the serotonergic specificity of the agent (R = .79, P = .021). CONCLUSIONS: Data for nine SSRI/SSNRIs suggest superiority of antidepressants relative to placebo for the treatment of pediatric anxiety disorders with a moderate effect size.

Web-based interventions for youth internalizing problems: a systematic review.

OBJECTIVE: To review published reports on Web-based treatment and prevention programs for depression, anxiety, and suicide prevention in children, adolescents, and emerging adults. METHOD: A systematic search of the PsycINFO, PubMed, Medline, and Web of Science databases was conducted in December 2013. Programs were classified according to evidence-base level (Well-Established, Probably Efficacious, Possibly Efficacious, Experimental, and Of Questionable Efficacy). RESULTS: Of the 14,001 citations initially identified, 25 articles met inclusion criteria for Web-based interventions. These described 9 programs, of which 8 were Internet based and 1 was a mobile application. No Web-based interventions for suicide prevention were identified. Of the randomized controlled trials (n = 14) and open trials (n = 3) identified, 10 reported significant postintervention reductions in symptoms of depression and/or anxiety or improvements in diagnostic ratings, with small to large effect sizes. Many of these studies also reported significant improvements at follow-up. The methodological quality of the studies varied. Many programs were limited by their small sample sizes and use of waitlist or no-treatment control groups. CONCLUSION: There is limited evidence for the effectiveness of Web-based interventions for youth depression and anxiety. Additional research and program development are needed to fill the current gaps in the literature.

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.

Remission of generalized anxiety disorder after 6 months of open-label treatment with venlafaxine XR.

BACKGROUND: Remission has become one of the leading outcome criteria in clinical trials. Data collected by this research group assessed the rate of remission after 6 months of treatment of generalized anxiety disorder (GAD) with venlafaxine XR, to search for predictors of remission and to define how early on in treatment later remission can be predicted. METHOD: Two hundred sixty-eight patients with a GAD diagnosis enrolled into an open-label 6-month-treatment trial with venlafaxine XR (75-225 mg/day). Remission was defined by a Hamilton anxiety scale total score ≤7. Logistic regression approaches were used to find out how early on in treatment later remission could be predicted, as well as to determine predictors of remission. In addition, adverse events were also followed over time. RESULTS: While the total enrolled patient sample (n = 268) had a remission rate of 53%, 6-month completers (n = 159) had a remission rate of 79%. The only statistically significant predictor of remission, independent of baseline anxiety and depression levels, was a low Eysenck neuroticism score. The remission status outcome could best be predicted after 8 weeks of treatment when a CGI-I score of 1 or 2 predicted later remission with 78% accuracy and later nonremission with 91% accuracy. The incidence of adverse events decreased over the 6-month period, with sexual adverse events decreasing the least. CONCLUSION: The only significant predictor of remission was a low score on the Eysenck neuroticism scale. The earliest reliable prediction of later remission, based on improvement, could be made after 8 weeks of treatment with 91% accuracy.

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.