Children's Depression Rating Scale-Revised Score Research Articles

Safety and Efficacy of Levomilnacipran Extended Release in Pediatric Patients Aged 7-17 Years with Major Depressive Disorder: Results of Two Phase 3, Randomized, Double-Blind Studies.

Objective: Major depressive disorder (MDD) presents a significant psychosocial burden, and there is an unmet need for additional treatment options in pediatric patients. Here, we report the results of two phase 3 multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group studies evaluating the efficacy and safety of levomilnacipran extended release in children and adolescents with MDD. Methods: In the first study, LVM-MD-11, patients aged 12-17 years received daily doses of levomilnacipran 40 mg (n = 134), levomilnacipran 80 mg (n = 138), fluoxetine 20 mg (n = 134), or placebo (n = 141). In the second study, LVM-MD-14, patients aged 7-17 years received levomilnacipran 40 to 80 mg (n = 166), fluoxetine 20 mg (n = 166), or placebo (n = 160) daily. Primary and secondary efficacy endpoints were changes in Children's Depression Rating Scale-Revised (CDRS-R) total score and Clinical Global Impressions-Severity (CGI-S) score, respectively. Results: In LVM-MD-11, there were no significant differences in change in CDRS-R total score between patients treated daily with placebo (least squares mean [LSM] change in CDRS-R total score -22.9) versus levomilnacipran 40 mg (-23.3; p = 0.8035) or 80 mg (-22.6; p = 0.8681). Similarly, in LVM-MD-14, there were no significant differences in LSM change in CDRS-R total score with placebo (-21.3) versus levomilnacipran 40 to 80 mg daily (-23.0; p = 0.2215). There were also no significant differences between the fluoxetine and placebo groups in either study for changes in CDRS-R total score. Changes in CGI-S score were not significant between placebo and levomilnacipran 40 to 80 mg daily or between placebo and fluoxetine. Levomilnacipran was generally well tolerated. Conclusions: The high placebo response in this study prevented the detection of an effect of levomilnacipran in children and adolescents. Clinical Trial Registration numbers: NCT02431806 and NCT03569475.

Clinical implication of children's depression rating scale-revised score: Linking the children's depression rating scale-revised score and clinical global impression using patients data from clinical trials.

The Children's Depression Rating Scale-Revised (CDRS-R) score has been widely used to assess the severity of major depression in children and adolescents; however, the clinical implications of changes in the CDRS-R score remain unclear. We evaluated these clinical implications by assessing the relationship between changes in the CDRS-R score and changes in the Clinical Global Impression of Improvement (CGI-I), in clinical research on major depression. We used data from four clinical trials involving two antidepressants and evaluated the relationship between CDRS-R score changes and the CGI-I score using the equipercentile linking method. CDRS-R score changes corresponding to a minimally improved (score of 3) CGI-I score was approximately 14 points. Our findings from the linking analyses are useful for interpreting the clinical implications of changes in the CDRS-R score.

A Characterization of the Clinical Global Impression Scale Thresholds in the Treatment of Adolescent Depression Across Multiple Rating Scales.

Introduction: The Clinical Global Impressions-Improvement (CGI-I) scale is widely used in clinical research to assess symptoms and functioning in the context of treatment. The correlates of the CGI-I with efficacy scales for adolescent major depressive disorder are poorly understood. This study focused on benchmarking CGI-I scores with changes in the Children's Depression Rating Scale-Revised (CDRS-R) and the Quick Inventory of Depressive Symptomatology-Adolescent (17-item) Self-Report (QIDS-A17-SR). Methods: We examined three datasets with the clinician-rated CDRS-R to ascertain equivalent percent changes in total scores and CGI-I ratings. Exploratory analyses examined corresponding percentage changes in the QIDS-A17-SR and the CGI-I ratings. The CGI-I was the reference scale for nonparametric equipercentile linking with the Equate package in R. Results: CGI-I scores of 1 mapped to ≥78%-95% change in CDRS-R scores at 4-6 weeks across three datasets. CGI-I scores of 2 mapped to 56%-94% change in CDRS-R scores at 4-6 weeks across three studies. CGI-I scores of 3 mapped to 30%-68% changes in CDRS-R scores at 4-6 weeks across three studies. CGI-I scores of 4 mapped to a range of 29%-44% at 4-6 weeks across three studies. There was no significant difference (p ≥ 0.6) between treatment groups in both the Treatment of Adolescents with Depression and Treatment of Resistant Depression in Adolescents studies, for each CGI-I score ( = 1, or = 2 or = 3, or ≥4), associated mapping of total depression severity score, or associated percent change from baseline for corresponding follow-up visits. There was no significant sex difference (p > 0.2) in CGI-I linkages to CDRS-R total or percentage changes. Conclusions: These findings establish clear relationships among CGI-I scores and the CDRS-R and the QIDS-A17-SR. These benchmarks have utility for clinical trial study design, inter-rater reliability training, and clinical implementation.

Item Response Analyses of the Children's Depression Rating Scale-Revised Using Data from Clinical Studies.

Objective: We aimed to identify which of the 17 items comprising the Children's Depression Rating Scale-Revised (CDRS-R) can sensitively capture changes in depression severity. Methods: We used data from four studies involving two antidepressants. For each of the 17 CDRS-R items, we conducted item response analyses to identify and evaluate those that reflect changes in depression severity. We created plots of the item characteristic curves (ICCs) estimated by the graded response model, and option characteristic curves and ICCs using nonparametric item response theory. The change from baseline in the CDRS-R subscale score with specified reflective items by item response analyses and the effect size between the treatment group and placebo group were calculated and compared with those of the CDRS-R total score. Results: CDRS-R items #2 (difficulty having fun), #3 (social withdrawal), #10 (low self-esteem), #11 (depressed feelings), and #15 (depressed facial expression) have favorable profiles that reflect disease severity. Changes from baseline in the CDRS-R total score (least square mean ± standard error) at week 8 were -22.3 ± 0.7 and -23.9 ± 0.7 in the placebo group and treatment group, respectively (difference, -1.5; estimated effect size, -0.113), changes from baseline in the CDRS-R5 (CDRS-R subscale consisting of the specified reflective items [#2, #3, #10, #11, and #15]) score at week 8 were -8.4 ± 0.3 and -9.6 ± 0.3 in each group, respectively (difference, -1.2; effect size, -0.202). Conclusions: The item response analyses clarified the properties of 17 items of the CDRS-R for major depressive disorder in children and adolescents. The CDRS-R5 might optimize the assessment of changes in overall depression severity and differentiation of treatment responses.

Efficacy and Safety of Duloxetine in Children and Adolescents with Major Depressive Disorder in Japan: A Randomized Double-Blind Placebo-Controlled Clinical Trial Followed by an Open-Label Long-Term Extension Trial.

Objective: The goal of this study was to evaluate the efficacy and safety of duloxetine in children and adolescents (9-17 years of age) with major depressive disorder (MDD) in Japan. Methods: This study consists of two clinical trials. First, a 6-week, randomized double-blind placebo-controlled clinical trial (RCT) was conducted. The primary endpoint of RCT was the change in Children's Depression Rating Scale-Revised (CDRS-R) total scores from baseline. Following RCT, an open-label long-term extension trial (OLE) was conducted to investigate the longer-term safety of duloxetine for ∼1 year. Results: In RCT, CDRS-R total score changes from baseline to 6 weeks after the start of administration (primary endpoint) were -21.03 in the duloxetine group (n = 74) and -22.42 in the placebo group (n = 74). No significant difference was observed in the primary endpoint between the groups (p = 0.5587). In addition, no significant difference was observed in secondary endpoints such as CDRS-R response rates. The proportion of patients with ≥1 treatment-emergent adverse event (TEAE) in RCT was significantly higher in the duloxetine group (78.7%) than in the placebo group (62.2%), and most were mild or moderate in severity. Changes in CDRS-R total scores during OLE, in consecutive patients from the duloxetine group in RCT (n = 63), or placebo group (n = 59) in RCT, and newly enrolled patients (n = 28), were -12.1, -11.3, and -17.8, respectively. The proportion of patients with ≥1 TEAE in OLE was 90.5%, 88.1%, and 89.3% in the respective groups, and most of them were mild or moderate in severity. Conclusions: Duloxetine did not show superiority to placebo in efficacy in children and adolescents with MDD in Japan. Overall reported TEAEs were consistent with the currently available duloxetine safety profile and no new safety finding was observed in the two clinical trials.

Inflammation, depressive symptoms, and emotion perception in adolescence

BackgroundIndividuals with depression often demonstrate an altered peripheral inflammatory profile, as well as emotion perception difficulties. However, correlations of inflammation with overall depression severity are inconsistent and inflammation may only contribute to specific symptoms. Moreover, measurement of the association between inflammation and emotion perception is sparse in adolescence, despite representing a formative window of emotional development and high-risk period for depression onset. MethodsSerum interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β were measured in 34 adolescents aged 12-17 with DSM-IV depressive disorders (DEP) and 29 healthy controls (HC). Participants were evaluated using the Children's Depression Rating Scale-Revised (CDRS-R) and symptom subscales were extracted based on factor analysis. Participants also completed a performance-based measure of emotion perception, the Facial Emotion Perception Test (FEPT), which assesses the accuracy of categorizing angry, fearful, sad, happy, and neutral facial emotions. ResultsIL-6 and TNF-α correlated with reported depressed mood and somatic symptoms, respectively, but not total CDRS-R score, anhedonia or observed mood, across both DEP and HC. DEP demonstrated lower accuracy for identifying angry facial expressions. Higher IL-6 was inversely related to accuracy and discrimination of angry and neutral faces across all participants. IL-1β was associated with reduced discrimination of fearful faces. ConclusionsInflammatory markers were sensitive to affective and somatic symptoms of depression and processing of emotional threat in adolescents. In particular, IL-6 was elevated in depressed adolescents and therefore may represent a specific target for modulating depressive symptoms and emotion processing

Emotion perception and theory of mind in adolescents with major depression.

The research of theory of mind (ToM) and emotion perception (EP) in adolescents with major depressive disorder (MDD) is scarce, and no study to date has investigated the association between EP and long-term outcomes of adolescents with MDD. The aim of the current study was to evaluate ToM and EP in adolescents with MDD, as compared to healthy controls (HCs). In addition, we aimed to assess the association between impairment in ToM and EP, depressive symptom severity, and long-term outcome in the MDD group. We compared the performance of 14 adolescents with MDD and 25 HC in the Facial Expression Recognition Task (FERT) and the Interpersonal Perception Task. We followed up with the MDD group 2 years later to assess the level of their depressive symptoms using the Children's Depression Rating Scale-Revised (CDRS-R). No differences were found between adolescents with MDD and HC in the ToM and FERT tasks. Also, within the MDD group, there was no association between the severity of depressive symptoms and task performance. In the MDD group, there was a significant correlation between lower levels of accuracy in the FERT during the index depressive episode and lower CDRS-R scores on follow-up 2 years later (r2 = 0.35, p = 0.021). EP impairments in adolescents with MDD might predict worse long-term outcome. Further research is needed to verify our findings and to assess for a possible neurobiological underpinning for the state and trait impairments in EP in adolescents with MDD.

Effects of Antidepressant Treatment on Symptom Measures of Attention in Adolescents with Depression: A Preliminary Open-Label Study.

Objective: The effects of selective serotonin reuptake inhibitor (SSRI) on deficits in attention and executive function in adolescents with major depressive disorder (MDD) are relatively unknown. We aimed to investigate changes in symptom measures of attention in adolescents with MDD treated with escitalopram. Methods: The study included 82 MDD adolescents and 54 healthy controls aged from 12 to 17 years. Symptom measures of attention were assessed using the Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) and Child Behavior Checklist attention problems scale at baseline and during week 8. Adolescents who showed at least 40% improvement in the Children's Depression Rating Scale-Revised (CDRS-R) scores from baseline to week 8 were referred to as "responders." Results: No baseline differences were found between the responders (n = 47) and nonresponders (n = 35) in their age, sex, intelligence quotient, CDRS-R score, and attention measures. Linear mixed models showed significant group-by-time interaction effect in the ADHD-RS inattention subscale score, but not in the other attention measures. Conclusion: Our results suggest that treating depressive symptoms with SSRI may lead to improvements in attention in MDD adolescents. Monitoring changes in symptom measures of attention can be useful when treating adolescents with MDD. ClinicalTrials.gov identifier: NCT03547219.

How Are Discrepant Parent-Child Reports Integrated? A Case of Depressed Adolescents.

Objective: Severity ratings of psychopathology in minors are often based on a composite score of the parent's and child's reports. However, parent's and child's reports often differ substantially, resulting in the integration method affecting the final scores. Nevertheless, effects of integration algorithms are seldom assessed and poorly understood. Method: The dataset is derived from the Treatment for Adolescents with Depression Study (TADS) and consists of 439 adolescents, 54% female, with a Major Depressive Disorder. The interviewer conducted the clinical interview Children's Depression Rating Scale-Revised (CDRS-R) with the parent and the adolescent and the TADS manual advised the interviewer to use the higher score as the final rating unless an informant was judged to be unreliable. Polynomial regressions, multivariate analyses, and mixed models were used to analyze the effects of this integration algorithm on the final scores and associated factors. Results: In 77% of the cases, the interviewer followed the TADS rating rule to use the higher CDRS-R item score. However, the final item scores differed significantly from the rule using the higher value, with the higher score being less often adapted at follow-up assessments and in female patients. Conclusions: The algorithm used to integrate divergent reports affects study outcomes and might introduce data-specific biases. Judgments of the validity and reliability of informants compromise the objectivity of outcomes in major clinical trials by introducing a subjective bias. Therefore, the agreement between children's and parent's reports and the method of integration should routinely be reported in research on pediatric psychopathology. ClinicalTrials.gov NCT00006286.

Treatment-Resistant Depression in Adolescents: Clinical Features and Measurement of Treatment Resistance.

Objective: To describe the clinical characteristics of adolescents with antidepressant treatment-resistant major depressive disorder (MDD) and to examine the utility of the Antidepressant Treatment Record (ATR) in categorizing treatment resistance in this population. Methods: Adolescents with treatment-resistant MDD enrolled in an interventional study underwent a baseline evaluation with the ATR, Children's Depression Rating Scale-Revised (CDRS-R), and Clinical Global Impressions-Severity (CGI-S) scales. Demographic and clinical characteristics were examined with regard to ATR-defined level of resistance (level 1 to ≥3) using analysis of variance and χ2 tests. Results: In adolescents with treatment-resistant MDD (N = 97), aged 12-21 years, most were female (65%), white (89%), and had recurrent illness (78%). Patients were severely ill (median CGI-S score of 5), had a mean CDRS-R score of 63 ± 10, and 17.5% had been hospitalized for depression-related symptoms. Fifty-two patients were classified as ATR 1, whereas 32 were classified as ATR level 2 and 13 patients as ≥3, respectively. For increasing ATR-defined levels, illness duration increased from 12.0 (range: 1.5-31.9) to 14.8 (range: 1.8-31.7) to 19.5 (range: 2.5-36.2) months and the likelihood of treatment with serotonin norepinephrine reuptake inhibitors (SNRIs) and dopamine norepinephrine reuptake inhibitors (DNRIs) similarly increased (p = 0.006 for both SNRIs and DNRIs) as did the likelihood of treatment with mixed dopamine serotonin receptor antagonists (χ2 = 17, p < 0.001). Conclusions: This study underscores the morbidity and chronicity of treatment-resistant MDD in adolescents. The present characterization of related clinical features describes the use of nonselective serotonin reuptake inhibitors in adolescents with treatment-resistant depression and raises the possibility that those with the greatest medication treatment resistance are less likely to have had recurrent episodes. The study also demonstrates the utility of the ATR in categorizing treatment resistance in adolescents with MDD.

Symptom clusters in adolescent depression and differential response to treatment: a secondary analysis of the Treatment for Adolescents with Depression Study randomised trial

Better understanding of the heterogeneity of treatment responses could help to improve care for adolescents with depression. We analysed data from a clinical trial to assess whether specific symptom clusters responded differently to various treatments. For this secondary analysis, we used data from the Treatment for Adolescents with Depression Study (TADS), in which 439 US adolescents aged 12-17 with a DSM-IV diagnosis of major depressive disorder and a minimum score of 45 on the Children's Depression Rating Scale-Revised (CDRS-R) were randomly assigned (1:1:1:1) to treatment with fluoxetine, cognitive behavioural therapy (CBT), fluoxetine plus CBT, or pill placebo. Our analysis focuses on the acute phase of the trial (ie, the first 12 weeks). Groups of co-occurring symptoms were established by clustering scores for each CDRS-R item at baseline with Ward's method, with Euclidean distances for hierarchical agglomerative clustering. We then used a linear mixed-effects model to investigate the relationship between symptom clusters and treatment efficacy, with the sum of symptom scores within each cluster as the dependent measure. As fixed effects, we entered cluster, time, and treatment assignment, with all two-way and three-way interactions, into the model. The random effect providing better fit was established to be a by-subject random slope for cluster based on improvement in the Schwarz-Bayesian information criterion. We identified two symptom clusters: cluster 1 comprised depressed mood, difficulty having fun, irritability, social withdrawal, sleep disturbance, impaired schoolwork, excessive fatigue, and low self-esteem, and cluster 2 comprised increased appetite, physical complaints, excessive weeping, decreased appetite, excessive guilt, morbid ideation, and suicidal ideation. For cluster 1 symptoms, CDRS-R scores were reduced by 5·8 points (95% CI 2·8-8·9) in adolescents treated with fluoxetine plus CBT, and by 4·1 points (1·1-7·1) in those treated with fluoxetine, compared with those given placebo. For cluster 2 symptoms, no significant differences in improvements in CDRS-R scores were detected between the active treatment and placebo groups. Response to fluoxetine and CBT among adolescents with depression is heterogeneous. Clinicians should consider clinical profile when selecting therapeutic modality. The contrast in response patterns between symptom clusters could provide opportunities to improve treatment efficacy by gearing the development of new therapies towards the resolution of specific symptoms. Conselho Nacional de Desenvolvimento Científico e Tecnológico.

Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study.

Novel interventions for treatment-resistant depression (TRD) in adolescents are urgently needed. Ketamine has been studied in adults with TRD, but little information is available for adolescents. This study investigated efficacy and tolerability of intravenous ketamine in adolescents with TRD, and explored clinical response predictors. Adolescents, 12-18 years of age, with TRD (failure to respond to two previous antidepressant trials) were administered six ketamine (0.5 mg/kg) infusions over 2 weeks. Clinical response was defined as a 50% decrease in Children's Depression Rating Scale-Revised (CDRS-R); remission was CDRS-R score ≤28. Tolerability assessment included monitoring vital signs and dissociative symptoms using the Clinician-Administered Dissociative States Scale (CADSS). Thirteen participants (mean age 16.9 years, range 14.5-18.8 years, eight biologically male) completed the protocol. Average decrease in CDRS-R was 42.5% (p = 0.0004). Five (38%) adolescents met criteria for clinical response. Three responders showed sustained remission at 6-week follow-up; relapse occurred within 2 weeks for the other two responders. Ketamine infusions were generally well tolerated; dissociative symptoms and hemodynamic symptoms were transient. Higher dose was a significant predictor of treatment response. These results demonstrate the potential role for ketamine in treating adolescents with TRD. Limitations include the open-label design and small sample; future research addressing these issues are needed to confirm these results. Additionally, evidence suggested a dose-response relationship; future studies are needed to optimize dose. Finally, questions remain regarding the long-term safety of ketamine as a depression treatment; more information is needed before broader clinical use.

A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Vilazodone in Adolescents with Major Depressive Disorder

BackgroundMajor depressive disorder (MDD) is a serious illness in children and adolescents. Vilazodone is a selective serotonin reuptake inhibitor approved for MDD in adults. This study evaluated the efficacy, safety, and tolerability of vilazodone in adolescent patients, ages 12–17 years, with MDD (NCT01878292).MethodsThis double-blind, randomized, placebo-controlled, parallel-group, fixed-dose study was conducted at 56 study centers in the United States and was 10 weeks in duration (a 1-week screening period, an 8-week double-blind treatment period, and a 1-week double-blind down-taper period). Outpatients with an MDD diagnosis based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria were included in the study. Clinical inclusion criteria required a Children’s Depression Rating Scale–Revised (CDRS-R) total score of ≥ 40 and Clinical Global Impressions–Severity (CGI-S) score of ≥ 4. Patients were randomized 1:1:1 to 8 weeks of double-blind treatment with placebo (n = 174), vilazodone 15 mg/day (n = 175), or vilazodone 30 mg/day (n = 180). The primary and secondary efficacy parameters were change from baseline to week 8 in CDRS-R total score and CGI-S score, respectively. Safety parameters included adverse events (AEs); clinical laboratory, vital sign, and electrocardiogram parameters; and the Columbia-Suicide Severity Rating Scale.ResultsApproximately 86% of patients completed double-blind treatment. There was no statistically significant difference between vilazodone 15 mg/day or 30 mg/day and placebo in change from baseline in CDRS-R score. Change in CGI-S score was not significant after adjustment for multiple comparisons. The most common treatment-emergent AEs were nausea, upper abdominal pain, vomiting, diarrhea, nasopharyngitis, headache, and dizziness. Reports of suicidal ideation (placebo, 33.3%; vilazodone 15 mg/day, 36.0%; vilazodone 30 mg/day, 31.1%) and suicidal behavior (placebo, 1.8%; vilazodone 15 mg/day, 1.1%; vilazodone 30 mg/day, 1.1%) were similar between treatment groups. There were no deaths in the study.ConclusionsThe efficacy of vilazodone for the treatment of MDD in adolescent patients could not be confirmed in this study. Vilazodone was generally safe and well tolerated, with treatment-emergent AEs similar to those in adult patients.Clinical Trial RegistrationNCT01878292.Electronic supplementary materialThe online version of this article (10.1007/s40272-018-0290-4) contains supplementary material, which is available to authorized users.

Psychometric properties of the Turkish adaptation of the Children's Depression Rating Scale: revised in Turkish adolescents

Objective: Children Depression Rating Scale-Revised (CDRS-R) is an instrument that is evaluated by a clinician and it needs bringing up the information from child/adolescent, parents and clinical assessment together. In clinical population, CDRS-R provides general information about depressive symptomatology and severity of depression also. The aim of this study was to translate and adapt of CDRS-R in Turkish and evaluate its psychometric properties in adolescence in Turkish population. Methods: Thirty-eight adolescents with major depressive disorders (MDD) and 38 healthy controls between 13 and 18 years old were recruited. Adolescents with at least some symptoms of depression were evaluated using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL)-Present and Lifetime by a child psychiatrist. A child psychiatrist completed the Children Depression Rating Scale-Revised (CDRS-R). The Clinical Global Impressions-Severity (CGI-S) and the Children’s Global Assessment Scale (CGAS) were also rated. The participants were asked to complete the self-report inventories and Beck Depression Inventory. Ratings from all available CDRS-R scores were examined for both the study group and healthy controls. Results: Cronbach’s alpha was found highly reliable. The interclass correlation coefficients ranged between 0.92 and 0.99 for each item, thus the inter-rater reliability was found statistically significant and highly correlated. We identified 16 factors whose eigenvalues were greater than one. The CDRS-R’s items common variables were within the range of 0.45 to 0.87. The CDRS-R, CGI-S, and CGAS scores were compared with the CDRS-R raw score and they were found highly correlated. During evaluation of concurrent validity, BDI’s sensitivity was 90.9%, and speci-ficity 87.8%, and the positive and negative predictive values were 88% and 90%, respectively. The sensitivity, spec-ificity, and positive and negative predictive values for the CDRS-R were significantly high (100%). Conclusion: We found that Turkish version of the CDRS-R had reliability and validity for use in the diagnosis and rating of severity of major depressive disorders in Turkish children and adolescents.

Efficacy and Safety of Lurasidone in Children and Adolescents With Bipolar I Depression: A Double-Blind, Placebo-Controlled Study

To evaluate the efficacy and safety of lurasidone in children and adolescents with bipolar depression. Patients 10 to 17 years old with a DSM-5 diagnosis of bipolar I depression were randomized to 6 weeks of double-blind treatment with flexible doses of lurasidone 20 to 80 mg/day. The primary endpoint was change frombaseline to week 6 in the Children's Depression Rating Scale-Revised (CDRS-R) total score,evaluated by amixed-model repeated-measures analysis. A total of 347 patients were randomized and received at least 1 dose of lurasidone (n= 175; mean age 14.2 years; mean dose 33.6 mg/day) or placebo (n= 172; mean age 14.3 years). At week 6, treatment with lurasidone was associated with statistically significant improvement compared with placebo in CDRS-R total score (-21.0 versus-15.3; p< .0001; effect size 0.45). Lurasidone also was associated with statistically significant improvement in the Clinical Global Impression-Bipolar Severity depression score (key secondary measure) and in measures of anxiety, quality of life, and global functioning. Study completion rates were 92.0% in the lurasidone group and 89.7% in the placebo group; discontinuation rates due to adverse events were the same for the 2 groups (1.7%). The 2 most common adverse events on lurasidone were nausea and somnolence. Treatment with lurasidone was associated with few effects on weight and metabolic parameters. In this placebo-controlled study, monotherapy with lurasidone, in the dose range of 20 to 80 mg/day, significantly decreased depressive symptoms in children and adolescents with bipolar depression. Lurasidone was well tolerated, with minimal effects on weight and metabolic parameters. Clinical trial registration information-Lurasidone Pediatric Bipolar Study; http://Clinicaltrials.gov; NCT02046369.

Psychometric Properties and Factor Structures of the Korean Version of Children's Depression Rating Scale-Revised.

The Children's Depression Rating Scale-Revised (CDRS-R) is a valid instrument for the assessment of depressive symptoms in youth, but this measure is yet to be validated in Korea. Thus, the present study aimed to evaluate the validity of the Korean version of the CDRS-R and to determine its factor structures. This study included 66 youths between 12 and 17 years of age who participated as part of an ongoing study investigating biomarkers of the antidepressant response and suicidal events in depressed youth. At baseline, the participants were assessed using the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL), CDRS-R, Children's Depression Inventory (CDI), Beck Depression Inventory (BDI), Clinical Global Impressions-Severity (CGI-S), Children's Global Assessment Scale (CGAS), and Child Behavior Checklist (CBCL). Based on their diagnosis, each participant was assessed either five (major depressive disorder [MDD], n = 36) or two (non-MDD, n = 30) more times with the CDRS-R, CDI, BDI, CGI-S, and CGAS; thus, 306 assessments were included in the final analyses of the present study. Pearson's r and Cronbach's α values were used to determine validity and internal consistency, and exploratory factor analysis was performed to determine the factor structures of the Korean version of the CDRS-R. The CDRS-R score was significantly correlated with scores on the K-SADS-PL depression subscale (r = 0.93, p < 0.01), CDI (r = 0.86, p < 0.01), BDI (r = 0.85, p < 0.01), CGI-S (r = 0.84, p < 0.01), and CGAS (r = -0.86, p < 0.01), indicating that this measure has strong criterion validity. In addition, the high correlation of the CDRS-R with the depression subscale of the CBCL (r = 0.67, p < 0.01) and lower correlations with the subscales of the CBCL that assess delinquent behavior, aggressive behavior, and externalizing problem support the discriminant validity of this instrument (rs ≤ 0.50, p < 0.01). Internal consistency was high, as evidenced by a Cronbach's α of 0.91, and the exploratory factor analysis revealed that the Korean version of the CDRS-R comprised three factors as follows: subjective depressed mood, daily functional impairment, and observed depressive affect. These factors differed from those used in previous studies, which were performed with the English version of the CDRS-R. This study of the Korean version of the CDRS-R provides initial promising data regarding its criterion validity, discriminant validity, internal consistency, and factor structures. These properties were significantly strong, which suggests that the Korean version of the CDRS-R is a valid and reliable instrument for the assessment of depressive symptoms in youth.

A Randomized Clinical Trial Comparing Family-Focused Treatment and Individual Supportive Therapy for Depression in Childhood and Early Adolescence

Despite the morbidity and negative outcomes associated with early-onset depression, few studies have examined the efficacy of psychosocial treatment for depressive disorders during childhood. Integrating family in treatment could have particularly salutary effects during this developmental period. This trial compared immediate posttreatment effects of family-focused treatment for childhood depression (FFT-CD) with those of individual supportive psychotherapy (IP) for children 7 to 14 years old with depressive disorders. Children were randomized to 15 sessions of FFT-CD (n= 67) or IP (n= 67) over 4 months. The primary treatment outcome was adequate clinical depression response, defined as at least a 50% decrease in score on the Children's Depression Rating Scale-Revised (CDRS-R). Additional outcomes included patient-centered outcomes (parent- and child-reported treatment satisfaction), remission (defined as CDRS-R score≤28), change in continuous CDRS-R score, and change in child and parent reports of depressive and non-depressive symptoms and social adjustment. Significant improvement was evident across groups for depressive and non-depressive symptoms, global response, and functioning and social adjustment. Compared with children randomized to IP, children randomized to FFT-CD showed higher rates of adequate clinical depression response (77.7% versus 59.9%; number needed to treat= 5.72; odds ratio 2.29; 95% CI 1.001-5.247; t= 1.97, p= .0498). Across treatments, families reported high satisfaction; compared with IP families, FFT-CD families reported greater knowledge and skills for managing depression. There were no significant differences between treatment arms on secondary outcomes. Results support the value of psychosocial intervention, emphasize the important role that families play, and highlight the potential for FFT-CD for supporting recovery in children with depression. Clinical trial registration information-Systems of Support Study for Childhood Depression; http://clinicaltrials.gov; NCT01159041.

Factors associated with depression severity in adolescence

IntroductionSevere depression is greatly impairing during adolescence and involves a high risk for suicidal behaviors.Objectives and aimsIdentify clinical and demographic factors associated with severity of depression in adolescents diagnosed with a major mood disorder so as to improve clinical treatment and prevent suicidal behaviors.MethodsWe analyzed factors associated with depression severity in 145 severely ill adolescents diagnosed with a major affective disorder using the K-SADS (Kiddie-Schedule for Affective Disorders and Schizophrenia) at the Mood Disorder Outpatient Program of Bambino Gesù Children's Hospital (Rome). Depressive and manic symptoms were rated with the CDRS-R (Children's Depression Rating Scale-Revised) and K-SADS-MRS (Mania Rating Scale), respectively. Bivariate comparisons were followed by multivariable linear regression modeling.ResultsDepression severity was greater among females than males (mean CDRS scores: 53.0 vs. 42.8; P &lt; 0.0001) and with major depressive versus bipolar disorder diagnosis (50.4 vs. 45.4; P = 0.001). Manic symptoms, including irritability, mood lability, crowded thoughts, delusions, and insomnia, were more likely with more severe depression; their number and severity correlated with CDRS-R total score (respectively, β = 1.53 and 5.44;both P &lt; 0.0001). Factors independently and significantly associated with CDRS-R depression score in multivariate modeling were:– presence of suicidal ideation;– absence of ADHD;– female sex;– greater number of manic symptoms.ConclusionsSevere depression was associated with manic symptoms and with suicidal ideation among adolescents diagnosed with either bipolar or major depressive disorders. This relationship should be considered in treatment planning and suicide prevention, including consideration of mood-stabilizing and antimanic agents in the treatment of severe adolescent depression.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Effect of 2 psychotherapies on depression and disease activity in pediatric Crohn's disease.

Crohn's disease (CD) is associated with depression. It is unclear if psychosocial interventions offer benefit for depressive symptoms during active CD. In this secondary analysis of a larger study of treating depression in pediatric inflammatory bowel disease, we assessed whether cognitive behavioral therapy (CBT) would differentiate from supportive nondirective therapy in treating depression and disease activity in youth with CD. We also explored whether somatic depressive symptoms showed a different pattern of response in the overall sample and the subset with active inflammatory bowel disease. Youth with depression and CD (n = 161) were randomized to 3 months of CBT (teaching coping skills) or supportive nondirective therapy (supportive listening). Depressive severity was measured using the Children's Depression Rating Scale-Revised (CDRS-R) with the somatic depressive subtype consisting of those CDRS-R items, which significantly correlated with CD activity. Disease activity was measured by the Pediatric Crohn's disease Activity Index. Given the potential confound of higher dose steroids, subanalyses excluded subjects on >20 mg/d prednisone equivalent (n = 34). Total CDRS-R scores in the overall sample significantly decreased over time after both treatments (P < 0.0001). Treatment with CBT was associated with a significantly greater improvement in the Pediatric Crohn's disease Activity Index (P = 0.05) and somatic depressive subtype (P = 0.03) in those with active inflammatory bowel disease (n = 95) compared with supportive nondirective therapy. After excluding those on steroids (n = 34), there was a significant improvement in total CDRS-R (P = 0.03) and in Pediatric Crohn's disease Activity Index (P = 0.03) after CBT. Psychotherapy may be a useful adjunct to treat depression in the context of CD-related inflammation in youth who are not concurrently on higher dose steroids.

Olanzapine/Fluoxetine Combination in Children and Adolescents With Bipolar I Depression: A Randomized, Double-Blind, Placebo-Controlled Trial

To assess the efficacy and safety of olanzapine/fluoxetine combination (OFC) for the acute treatment of bipolar depression in children and adolescents. Patients 10 to 17 years of age with bipolar I disorder (BP-I), depressed episode, baseline Children's Depression Rating Scale-Revised (CDRS-R) total score≥40, Young Mania Rating Scale (YMRS) total score≤15, and YMRS-item 1≤2 were randomized to OFC (6/25-12/50 mg/day olanzapine/fluoxetine; n= 170) or placebo (n= 85) for up to 8 weeks of double-blind treatment. The primary efficacy measure was mean change in CDRS-R using mixed-model repeated-measures methodology. Baseline-to-week-8 least-squares mean change in CDRS-R total score was greater for OFC-treated patients than for placebo-treated patients (-28.4 versus-23.4, p = .003; effect size= .46), with between-group differences statistically significant at week 1 (p= .02) and all subsequent visits (all p< .01). Rates of and times to response and remission were statistically significantly greater for OFC- than for placebo-treated patients. The most frequent treatment-emergent adverse events in the OFC group were weight gain, increased appetite, and somnolence. Mean weight gain at patient's endpoint was significantly greater for OFC- than for placebo-treated patients (4.4 kg versus 0.5 kg, p< .001). Treatment-emergent hyperlipidemia was very common among OFC-treated patients. Abnormal increases in hepatic analytes, prolactin, and corrected QT interval (QTc) were also common or very common but generally not clinically significant. In this study, OFC was superior to placebo, and has been approved by the US Food and Drug Administration (FDA) for the acute treatment of bipolar I depression in patients 10 to 17 years of age. Benefits should be weighed against the risk of adverse events, particularly weight gain and hyperlipidemia. Clinical trial registration information-A Study for Assessing Treatment of Patients Ages 10-17 with Bipolar Depression; http://clinicaltrials.gov; NCT00844857.