Children's Depression Rating Scale-Revised Research Articles

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.

Prevalence and Diagnostic Tools Predictability of Common Mental Disorders among Indian Children and Adolescent Population

The objective of this systematic review was to examine the pooled prevalence of common mental disorder (CMD) and to evaluate the predictability of screening instruments to detect CMD in the children and adolescent population in India. Data sources included the MEDLINE, PubMed, PyschEXTRA, and PyschINFO up to 2020, with additional studies identified from a search of reference lists to examine the diagnostic utility of tools carried out in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, PRISMA within parentheses after the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines (PRISMA). Only studies involving children and adolescents with an independent measure of depression and anxiety in India were included. Random effects meta-analyses were employed to calculate a pooled estimate of depression prevalence. Twenty studies met all inclusion and exclusion criteria for the systematic review. The analysis showed that several tools were used in different regions of the nation to measure CMD such as the beck depression inventory (BDI), Children's Depression Rating Scale-Revised (CDRS-R), and Depression Anxiety Stress Scale. The pooled prevalence of depression was 19% (95% confidence interval (CI) = 12.57–27.12), 15% (95% CI = 4.67–30.90) for anxiety, and 11% (95% CI = 4.37–19.77) for any depressive disorder. In terms of BDI had the highest sensitivity (61%) while CDRS-R had the highest specificity (75%). Given the high heterogeneity of the studies, there is insufficient evidence that any tool accurately screens for CMD and likely to underestimate the true prevalence.

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.

Depression in adolescents exposed to war trauma Risk factors for development of depression in adolescents exposed to war trauma: does PTSD matter?

Background: Depression is frequently comorbid with posttraumatic stress disorder (PTSD) and substantially influences its severity, course and outcomes. Published studies linking war-related paediatric PTSD and Major depressive disorder (MDD) were mainly based on cross-sectional studies. Objective: To prospectively examine the role of PTSD and other risk/protective factors in the development of depression among adolescents with war-related trauma. Methods: A longitudinal study of 160 adolescents aged 15–17 years with war-related trauma and displacement due to war in Eastern Ukraine was performed. Of the 160 adolescents, N = 86 met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-4) criteria for PTSD. All adolescents underwent comprehensive psychiatric assessments that included Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL) administered to both parents and children. Traumatic exposure was assessed using the modified Traumatic Events Screening Inventory for children (TESI-C). PTSD and MDD were assessed with the Clinician-Administered PTSD Scale for Children and Adolescents (CAPS-CA) and Children’s Depression Rating Scale-Revised (CDRS-R), and diagnosed using DSM-4 criteria. Follow-up and repeated measurements occurred at 6 and 12 months. During the study, adolescents requiring clinical care were referred for best available care in the community. Results: Among 92.6% of study completers, 26/79 youth with PTSD developed MDD (32.9%), compared to 6/70 without PTSD (8.5%): relative risk (RR) = 3.83 (95% CI 1.67-8.78), p = 0.0014; Number needed to harm (NNTH) = 4.108 (8.53–2.7). Using logistic regression, variables of school attendance, ‘secondary’ traumatic exposure, and treatment with Trauma-focused Cognitive Behavioral Therapy (TF-CBT) were significantly correlated with the incidence of new-onset depression among adolescents with PTSD. Conclusions: War-related trauma with subsequent PTSD appears to be a significant risk factor for the later development of depression in adolescents. The role of PTSD as a moderator of depression merits further investigation in larger scale longitudinal studies in diverse populations.

A CROSS SECTIONAL DESCRIPTIVE STUDY OF OCD IN CHILDREN AND ADOLESCENTS

This study was a part of a bigger multicentric study to examine the socio-demographic and clinical characteristics of children and adolescents (age ≤18 years) with OCD. Our sample comprised 30 subjects with OCD. Socio-demographic data was collected on a proforma specifically designed for this study. Clinical information was obtained on Structured clinical interview for Diagnostic and Statistical Manual, 5th edition Research Version (SCID), Children’s Yale Brown Obsessive Compulsive Scale (CYBOCS), the Children’s Depression Rating Scale–Revised (CDRS) and the Family Interview for Genetic Studies (FIGS). In our sample 70% of participants were male and 67.7% had onset of symptoms before 14 years of age. Most common obsessions in our participants were of doubts about contamination and magical thinking/superstitious while the most common compulsions were those involving checking, washing and rituals involving other persons. Comorbid psychiatric disorders were seen in 63.3% patients with most common being depression, Obsessive Compulsive Related Disorders (OCRDs), intermittent explosive disorder and anxiety disorder. The associated OCD symptoms on CYBOCS including lack of insight, avoidance and indecisiveness were on a spectrum. 46.6% had positive family history of OCD in first degree relative.

Temporal precedence of the change in obsessive-compulsive symptoms and change in depressive symptoms during exposure and response prevention for pediatric obsessive-compulsive disorders

The current study examined the temporal precedence of change in obsessive-compulsive symptoms and change in depressive symptoms during the course of an Exposure and Response Prevention (ERP) for pediatric OCD. Participants included 142 children and adolescents (7–17 years; mean age = 12.39, SD = 2.92; 51.40% female; 60.40% Non-Hispanic White) with a primary or co-primary diagnosis of OCD who received ERP in a two-site randomized controlled trial on d-cycloserine augmentation of CBT for pediatric OCD. Participants completed clinician-administered assessments of OC symptoms (Children's Yale-Brown Obsessive Compulsive Scale) and depressive symptoms (Children's Depression Rating Scale-Revised) from baseline to post-treatment follow-up. Lagged mediational analyses did not yield evidence in support of a mediating role for the change in OC symptoms in the effect of ERP on the change in depressive symptoms. In contrast, change in depressive symptoms mediated the effect of ERP treatment on the subsequent change in OC symptoms (95% confidence interval for indirect effect = −0.04 to −0.001), though the effect size was small. Controlling for the prior levels of the depressive symptoms this indirect effect became non-significant. Theoretical and clinical implications of the findings for the youth with OCD and comorbid depression are discussed.

Depression in adolescents exposed to war trauma Risk factors for development of depression in adolescents exposed to war trauma: does PTSD matter?

Abstract Background Depression is frequently comorbid with posttraumatic stress disorder (PTSD) and substantially influences its severity, course and outcomes. Published studies linking war-related paediatric PTSD and Major depressive disorder (MDD) were mainly based on cross-sectional studies. Objective To prospectively examine the role of PTSD and other risk/protective factors in the development of depression among adolescents with war-related trauma. Methods A longitudinal study of 160 adolescents aged 15–17 years with war-related trauma and displacement due to war in Eastern Ukraine was performed. Of the 160 adolescents, N = 86 met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-4) criteria for PTSD. All adolescents underwent comprehensive psychiatric assessments that included Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL) administered to both parents and children. Traumatic exposure was assessed using the modified Traumatic Events Screening Inventory for children (TESI-C). PTSD and MDD were assessed with the Clinician-Administered PTSD Scale for Children and Adolescents (CAPS-CA) and Children's Depression Rating Scale-Revised (CDRS-R), and diagnosed using DSM-4 criteria. Follow-up and repeated measurements occurred at 6 and 12 months. During the study, adolescents requiring clinical care were referred for best available care in the community. Results Among 92.6% of study completers, 26/79 youth with PTSD developed MDD (32.9%), compared to 6/70 without PTSD (8.5%): relative risk (RR) = 3.83 (95% CI 1.67–8.78), p = 0.0014; Number needed to harm (NNTH) = 4.108 (8.53–2.7). Using logistic regression, variables of school attendance, ‘secondary’ traumatic exposure, and treatment with Trauma-focused Cognitive Behavioral Therapy (TF-CBT) were significantly correlated with the incidence of new-onset depression among adolescents with PTSD. Conclusions War-related trauma with subsequent PTSD appears to be a significant risk factor for the later development of depression in adolescents. The role of PTSD as a moderator of depression merits further investigation in larger scale longitudinal studies in diverse populations.

Fluoxetine in the Management of Major Depressive Disorder in Children and Adolescents: A Meta-Analysis of Randomized Controlled Trials.

Fluoxetine is a serotonin-specific reuptake inhibitor antidepressant and is the only approved pharmacological treatment for major depressive disorder (MDD) in children and adolescent. We searched the published randomized controlled-trials to review fluoxetine efficacy and tolerability using the databases PubMed, EudraCT, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials for fluoxetine role in managing MDD in children and adolescents. A meta-analysis was conducted using the identified 7 clinical trials to assess efficacy using the outcomes: Children's Depression Rating Scale-Revised (CDRS-R), Clinical Global Impressions-Severity of Illness (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) response rate. The risk of discontinuation due to adverse effects and common side effects were examined. The mean difference in change from baseline for CDRS-R was -2.72 (95% confidence interval [CI], -3.96, -1.48) favoring fluoxetine treatment (P < .001). Similarly, mean difference for CGI-S was -0.21 (95% CI, -0.36, -0.06). The risk ratio (RR) of discontinuing due to adverse events was 0.98 (95% CI, 0.54, 1.83), with RR for headache side effects 1.34 (95% CI, 1.03, 1.74) and rash 2.6 (95% CI, 1.32, 5.14). Fluoxetine demonstrates significant improvements in symptom intensity control in young patients suffering from MDD and is considered well tolerated with similar rates of trials discontinuation; however, fluoxetine was associated with a higher risk of headache and rash side effects. These findings will guide psychiatrists and pharmacists in their clinical role for supporting the care of young mental health patients.

Efficacy and Safety of Quetiapine for Pediatric Bipolar Depression: A Systematic Review of Randomized Clinical Trials.

Quetiapine is a second-generation antipsychotic (SGA) approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia, mania, and aggression in children and adolescents. It is also commonly used as an off-label medication to treat children and adolescents with bipolar depression, although the FDA has not approved quetiapine for this purpose. We conducted a systematic review of randomized clinical trials (RCTs) using the MEDLINE database and included two studies that met our inclusion criteria. Both RCTs were eight-week short-term studies that involved patients of 10-18 years of age with a Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnosis of bipolar disorder, depressed type. The mean difference in the Children's Depression Rating Scale-Revised (CDRS-R) score and the response and remission rates in the quetiapine group were not statistically significant when compared to the placebo group. A high placebo response rate proved that quetiapine was no better than the placebo in treating pediatric bipolar depression. Quetiapine proved to be a relatively safe drug with the most common side effects being headache, somnolence, gastric upset, and weight gain. There was a significant increase in triglyceride levels, but no other metabolic effects were reported. This calls for future studies with larger sample sizes and improved methodology to explore the efficacy of quetiapine and other SGAs for the management of pediatric bipolar depression.

When parents and children disagree: Informant discrepancies in reports of depressive symptoms in clinical interviews

BackgroundParents and their children often disagree on the existence and severity of psychopathological symptoms, especially in major depressive disorder (MDD). Discrepant estimations pose a problem for the validity of diagnoses and illness severity with major implications for treatment evaluation. Methods118 adolescents aged 13–18 years and their parents were interviewed and their reports were compared regarding the presence of a MDD diagnosis. In addition, severity ratings of depression symptoms reported in the Children's Depression Rating Scale-Revised (CDRS-R) were compared between parents and their offspring using multivariate analyses and polynomial regressions. The association between borderline features, functional impairment, and treatment history variables with parent-child agreement was assessed. ResultsIn 38% of the cases, parents and adolescents agreed on DSM-IV diagnostic MDD criteria, while in 53%, only the adolescent endorsed criteria for a MDD. A MDD that was endorsed by parents and adolescents was characterized by higher depression severity, higher number of previous treatments, and higher functional impairment. Using a polynomial approach, neither age nor borderline tendencies were associated with agreement. LimitationsWe did not differentiate between mother's versus father's reports and borderline features were assessed by self-report only. ConclusionsAdolescents and their parents gave differing reports of the existence and severity of depressive symptoms. The high discrepancy levels combined with the uncertainty of previously published findings due to methodological challenges are concerning. Clinicians and researchers need to consider discrepancies in agreement in relation to diagnosis and illness severity in the context of their clinical and research decisions.

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.

159 Safety and Efficacy of Lurasidone in Children and Adolescents with Bipolar Depression: Results from a 2-Year Open-label Extension Study

Bipolar I disorder frequently has an early onset, with an estimated prevalence rate of 1.8% in pediatric populations. Early onset is associated with a high degree of chronicity; however, limited data are available on the long-term efficacy of drug therapies in pediatric populations. The aim of the current study was to evaluate the long-term safety and efficacy of lurasidone in children and adolescents with bipolar depression. Patients 10-17 years with bipolar I depression were randomized to 6 weeks of double-blind (DB) treatment with lurasidone or placebo. Patients who completed the study were eligible to enroll in a 2-year, open-label (OL) extension study in which patients were continued on flexibly-dosed lurasidone (20-80 mg/d; LUR-LUR) or switched from placebo to lurasidone (PBO-LUR). The primary efficacy measure was the Children's Depression Rating Scale, Revised (CDRS-R); response was defined as ≥50% reduction from DB baseline in the CDRS-R total score. A total of 306 patients completed the 6-week DB study and entered the extension study; 195 (63.7%) completed 52 weeks, and 168 (54.9%) completed 104 weeks of treatment. Mean CDRS-R total score at DB baseline was 59.4 in patients treated with lurasidone, and 58.7 in patients treated with placebo; and mean CDRS-R total score at OL baseline (after 6 weeks of DB treatment) was 36.6 in the LUR-LUR group and 41.9 in the PBO-LUR group. For the total sample of patients in the OL study, mean change (from OL baseline) in the CDRS-R score was -13.4 at week 52 and -16.4 at week 104; and responder rates were 51.0% at OL baseline (64.5% for LUR-LUR; 36.9% for PBO-LUR), 88.4% at week 52, and 91.1% at week 104. During OL treatment with lurasidone, 31 patients (10.1%) discontinued due to an adverse event. The most commonly reported events were headache (23.9%), nausea (16.4%), and somnolence (9.8%). OL treatment with lurasidone was associated with few effects on metabolic parameters or prolactin. Mean change from DB baseline in weight was +4.25 kg at week 52 (vs. an expected weight gain of 3.76 kg based on CDC normative data), and +6.75 kg at week 104 (vs. CDC expected weight gain of 6.67 kg). Two years of treatment with lurasidone in children and adolescents with bipolar depression was generally well-tolerated, with relatively low rates of study discontinuation. Lurasidone treatment was associated with few effects on weight, metabolic parameters, and prolactin. Patients also continued to experience improvement in depressive symptoms during long-term treatment with lurasidone.Clinicaltrials.gov identifier: NCT01914393. Supported by funding from Sunovion Pharmaceuticals Inc.

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.

Early changes of serum BDNF and SSRI response in adolescents with major depressive disorder

BackgroundRecent evidence suggests that brain-derived neurotrophic factor (BDNF) levels and their early changes may predict antidepressant response in adults with major depressive disorder (MDD). However, in adolescents, BDNF levels in depression and their changes during antidepressant treatment are relatively unknown. We aimed to investigate whether pre-treatment BDNF levels and their early changes predict antidepressant response in depressed adolescents. MethodsThe study included 83 MDD adolescents and 52 healthy controls aged 12 to 17 years. All depressed adolescents were treated with escitalopram in an 8 week, open-label trial. Depression severity and serum BDNF level at baseline, and weeks 2 and 8 were measured with the Children's Depression Rating Scale-Revised (CDRS-R) and ELISA, respectively. ResultsResponders showed a significant decrease in BDNF levels at week 2 but non-responders and healthy controls had no changes in BDNF levels at week 2. The early decrease (baseline – week 2) of BDNF levels predicted SSRI response with moderate sensitivity and specificity. Logistic regression analysis revealed that early BDNF decrease predicted SSRI response at week 8 after controlling for other demographic and clinical variables. LimitationsThe follow-up duration of the study was limited in 8 weeks. It remains possible that serum BDNF levels would have changed with longer treatment. ConclusionsThis is the first longitudinal study to investigate the effect of antidepressants on BDNF levels in adolescents with MDD. Our findings suggest that a decrease of serum BDNF levels in early phase of SSRI treatment may be associated later SSRI response in adolescents with MDD.

C-reactive protein and response to lurasidone treatment in children and adolescents with bipolar I depression: Results from a placebo-controlled trial

This study sought to investigate associations between levels of high-sensitivity c-reactive protein (hsCRP) prior to treatment and change in depressive symptoms and cognition in a short-term, double-blind, placebo-controlled study of lurasidone in children and adolescents with bipolar I depression. Patients 10–17 years of age with a DSM-5 diagnosis of bipolar I depression were randomized to 6 weeks of double-blind treatment with flexibly dosed lurasidone (20–80 mg/day) (n = 173) or placebo (n = 170). The primary efficacy measure was change from baseline to week 6 in the Children’s Depression Rating Scale, Revised (CDRS-R). Treatment response was defined as 50% or greater improvement on the CDRS-R from baseline to week 6. Cognitive function was evaluated with the computerized Brief Cogstate Battery at baseline and week 6. Analyses were adjusted for baseline BMI, as well as age. HsCRP was evaluated as a logarithmically transformed continuous variable and as a categorical variable dichotomized into lower (<1 mg/L) and higher (≥1 mg/L) subgroups. A significant interaction was found between baseline hsCRP and treatment group for change in CDRS-R score at study endpoint, with larger placebo-corrected effect sizes for lurasidone in the higher baseline hsCRP group (≥1 mg/L). A significant BMI-by-hsCRP-by-treatment interaction was found for response rate with higher baseline hsCRP levels associated with greater antidepressant response to lurasidone (vs. placebo) in the normal BMI range subgroup (NNT = 2 in higher hsCRP vs. NNT = 5 in lower hsCRP groups) but not in the overweight/obese patients (NNT = 6 in higher hsCRP vs. NNT = 5 in lower hsCRP). Similarly, a significant interaction effect was observed for the combination of hsCRP and BMI on the procognitive effect of lurasidone, with higher baseline hsCRP levels being associated with improvement in cognitive function for lurasidone (vs placebo) in the normal BMI range subgroup but not in overweight/obese patients. These results suggest that young patients with bipolar depression with normal weight and higher levels of pre-treatment CRP may show a greater placebo-adjusted improvement in depressive symptoms and cognitive performance when treated with lurasidone. If these findings are confirmed in future prospective studies, CRP and BMI may prove to be useful diagnostic and predictive biomarkers in the treatment with lurasidone of children and adolescents with bipolar depression.

Improvement in hypersomnia with high frequency repetitive transcranial magnetic stimulation in depressed adolescents: Preliminary evidence from an open-label study

Study objectivesSleep disruption is a significant symptom of major depressive disorder (MDD). To our knowledge, no prior work has examined the impact of repetitive transcranial magnetic stimulation (rTMS) on sleep disturbances in adolescents with MDD. MethodsSeventeen adolescents with treatment-resistant depression received 30 daily sessions of 10-Hz rTMS applied to the left dorsolateral prefrontal cortex (L-DLPFC). Clinical symptoms were assessed at baseline; after 10, 20, and 30 treatments; and at a 6-month follow-up visit. Insomnia was measured with a 3-item subscale of the Quick Inventory of Depressive Symptomatology–Adolescent (17 Item)–Self Report (QIDS-A17-SR). Hypersomnia was measured with a single QIDS-A17-SR item. Depression severity was rated with the Children's Depression Rating Scale, Revised (CDRS-R). The effect of rTMS on sleep was examined via linear mixed model analyses, with fixed effects of time (as a proxy of treatment), depression severity, age, and hypnotic medication use. ResultsNo significant main effect of time was observed on the insomnia subscale (F4,43.442 = 1.078, p = 0 .379). However, there was a significant main effect of time on the QIDS-A17-SR hypersomnia score (F4,46.124 = 2.733, p = 0 .040), with significant improvement from baseline to treatment 10 (padj = 0.019) and from baseline to 6-month follow-up (padj = 0.044). In exploratory sensitivity analyses, response/nonresponse to rTMS for overall depressive symptoms had no significant effect on sleep outcomes. ConclusionsrTMS may have intrinsic effects on hypersomnia apart from its antidepressant effects in depressed adolescents. Future work should utilize sham controls and objective, quantitative measurements of sleep architecture to assess effects of rTMS in depressed adolescents. Clinical trial registryClinicaltrials.gov identifiers are NCT00587639, NCT01502033, NCT01804270.

The clinical usefulness of three depression screens for adolescents in India: A need in primary-care settings.

Introduction:Adolescent Depression (AD) although is widely prevalent and is a prioritized disorder, it is under-diagnosed and under reported in primary-care. We document the post-test probability of three measures and select the best measure for identifying AD in primary-care settings in India based on the clinical utility.Materials and Methods:Three measures have been validated in India for AD and thus can be further evaluated for primary-care use; we calculated the positive (+PTP) and negative (-PTP) post-test probability from the prevalence of AD in India for Beck Depression Inventory-21 item version (BDI-21), Patient Health Questionnaire-9 item version (PHQ-9), and Children's Depression Rating Scale-Revised version (CDRS-R) using the Bayes theorem. The usefulness of the measure was defined a priori based on the odds ratio (OR) of +PTP (OR > 3) and −PTP (OR < 0.1).Results:The +PTP and −PTP for BDI-21 was 43% (95%CI = 40, 45%; OR = 0.7) and 25% (95%CI = 13, 43%; OR = 0.3) respectively. Similarly, the +PTP and − PTP for PHQ-9 was 74% (95%CI = 66, 81%; OR = 2.9) and 10% (95%CI = 6, 17%; OR = 0.1). Finally, +PTP and − PTP for CDRS-R was 78% (95%CI = 69, 84%; OR = 3.5) and 12% (95%CI = 7, 18%; OR = 0.1). Only CDRS-R achieved the useful decided a priori as can be seen in the Fagan's Nomograms.Conclusion:This research provides the evidence base for selecting CDRS-R as the screening measure, for Adolescent Depression, for clinical use in Primary-care settings in India.

Gut permeability and depressive symptom severity in unmedicated adolescents.

This study examined gut permeability in unmedicated adolescents with and without major depressive disorder. Medically healthy, non-medicated, 12-17 year-old females in a major depressive episode (MDE) or healthy controls, without any psychiatric condition, were enrolled. They completed the Children's Depression Rating Scale-Revised (CDRS-R) and underwent a clinical interview. Preejection period (PEP) and respiratory sinus arrhythmia (RSA) data were collected to measure autonomic nervous system activity. Following an overnight fast, participants ingested lactulose and mannitol and collected urine for 4 hours while still fasting, to examine gut permeability. Plasma cytokines (interleukin 1β, interleukin 6, and tumor necrosis factor α) were measured. Correlational analyses were used to examine the associations between relevant variables. 41 female participants (age: 14.8 ± 1.6 years, n = 25 with MDE) were enrolled. PEP, but not RSA, was inversely associated with neurovegetative symptom severity on the CDRS-R (r = -0.31, p < 0.06). In the 30 participants with gut permeability data, the lactulose to mannitol ratio (LMR) was significantly positively associated with depression severity, particularly neurovegetative symptom severity (r = 0.37, p < 0.05). Notably, the association between neurovegetative symptom severity and PEP was substantially reduced after adjusting for LMR. Additionally, depression severity was significantly associated with circulating cytokines. This is the first study to examine gut permeability in unmedicated adolescents, offering preliminary support for a mechanistic pathway linking sympathetic nervous system activation to increased gut permeability and activation of the innate immune system, likely contributing to the emergence of neurovegetative symptoms of depression.

Safety, Tolerability, and Efficacy of Desvenlafaxine in Children and Adolescents with Major Depressive Disorder: Results from Two Open-Label Extension Trials.

Two similarly designed extension studies evaluated the long-term safety and tolerability of desvenlafaxine for the treatment of children and adolescents with major depressive disorder (MDD). Efficacy was evaluated as a secondary objective. Both 6-month, open-label, flexible-dose extension studies enrolled children and adolescents who had completed one of two double-blind, placebo-controlled, lead-in studies. One lead-in study included a 1-week transition period prior to the extension study. Patients received 26-week treatment with flexible-dose desvenlafaxine (20-50 mg/d). Safety assessments included comprehensive psychiatric evaluations, vital sign assessments, laboratory evaluations, 12-lead electrocardiogram, physical examination with Tanner assessment, and Columbia-Suicide Severity Rating Scale. Adverse events (AEs) were collected throughout the studies. Efficacy was assessed using the Children's Depression Rating Scale-Revised (CDRS-R). A total of 552 patients enrolled (completion rates: 66.4 and 69.1%). AEs were reported by 79.4 and 79.1% of patients in the two studies; 8.9 and 5.2% discontinued due to AEs. Treatment-emergent suicidal ideation or behavior was reported for 16.6 and 14.1% of patients in the two studies. Mean (SD) CDRS-R total score decreased from 33.83 (11.93) and 30.92 (10.20) at the extension study baseline to 24.31 (7.48) and 24.92 (8.45), respectively, at week 26. Desvenlafaxine 20 to 50 mg/d was generally safe and well tolerated with no new safety signals identified in children and adolescents with MDD who received up to 6 months of treatment in these studies. Patients maintained the reduction in severity of depressive symptoms observed in all treatment groups at the end of the lead-in study.

Psychometric Properties of the Patient Health Questionnaire-9 Modified for Major Depressive Disorder in Adolescents.

The Patient Health Questionnaire-9 Modified (PHQ-9M) is a self-report tool used to assess the presence and severity of depressive symptoms in teenagers. Despite widespread use in primary care clinics and psychiatric settings, the PHQ-9M has not been validated nor are its psychometric properties adequately understood for the adolescent population. This study sought to examine the psychometrics of the PHQ-9M in treatment-seeking, depressed adolescents at a psychiatric psychopharmacology clinic who were concurrently assessed with the Children's Depression Rating Scale Revised (CDRS-R) and Quick Inventory of Depressive Symptomatology-Adolescent (17-item) Self-Report (QIDS-A17-SR). Adolescents (N = 160) aged 13 through 18 years with a diagnosis of major depressive disorder, determined on the basis of a clinical interview and semi-structured interview using the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version, were assessed for severity of depressive symptoms with the PHQ-9M, CDRS-R (adolescent interview only), and QIDS-A17-SR assessments at baseline, 4, and 8 weeks. Classical test theory analysis was used to evaluate the internal consistency and dimensionality of the PHQ-9M. Convergent validity was evaluated via intraclass correlations of the PHQ-9M with the CDRS-R and QIDS-A17-SR. Sensitivity to treatment response was also evaluated. The internal consistency (Cronbach's coefficient α) at baseline, 4, and 8 weeks was 0.879, 0.859, and 0.827 for the PHQ-9M; 0.739, 0.835, and 0.867 for CDRS-R; and 0.712, 0.777, and 0.804 for QIDS-A17-SR, respectively. The PHQ-9M had moderate convergent validity with the CDRS-R but good convergent validity with the QIDS-A17-SR. The PHQ-9M was less sensitive to changes in symptom severity than the CDRS-R and QIDS-A17-SR. The PHQ-9M appears to be a valid and reliable assessment tool for the severity of depressive symptoms in a psychiatric clinic setting. However, its utility as a treatment outcome measure may be limited compared with other available rating scales.