Children's Depression Rating Scale-Revised Research Articles

Depression severity and verbal comprehension in children and adolescents with a major depressive episode

IntroductionSevere depression is a prevalent psychiatric illness in children and adolescents associated with high levels of morbidity, disability, and a high risk of suicidal behavior. Cognitive factors associated with depression severity in juveniles have been poorly reported. MethodsWe investigated the relationship between depression severity and intelligence quotient (IQ)with its subscales in 65 juveniles (aged 10–17 years) with a current major depressive episode evaluated at the Mood Disorder Program of Bambino Gesù Children’s Hospital in Rome. Pearson’s correlation analyses were followed by a Benjamini–Hochberg correction and linear multivariable regression model. ResultsDepression severity measured with the total score of the Children’s Depression Rating Scale-Revised (CDRS-R) was positively associated with the Verbal Comprehension Index (VCI; Pearson’s r = 0.309 [0.042−0.534]; p = 0.024). The CDRS-R subscales positively associated with VCI by Pearson’s correlation were depressed feelings, suicidal ideation, excessive weeping, and reduced facial expressions. Suicidal ideation was the only factor independently and significantly associated with higher VCI in the multivariable linear regression model.DiscussionSuicidal ideation was significantly and independently associated with higher verbal comprehension, indicating that depressed juveniles with better verbal ability may be at a greater risk of showing suicidal ideation.

A Dose-Finding, Biomarker Validation, and Effectiveness Study of Transcranial Magnetic Stimulation for Adolescents With Depression

Research and clinical application of transcranial magnetic stimulation (TMS) for adolescents with major depressive disorder (MDD) has advanced slowly. Significant gaps persist in our understanding of optimized, age-specific protocols and dosing strategies. This study aimed to compare the clinical effects of 1 Hz versus 10 Hz TMS regimens and examine a biomarker-informed treatment approach with glutamatergic intracortical facilitation (ICF). Participants with moderate-to-severe symptoms of MDD were randomized to 30 sessions of left prefrontal 1 Hz or 10 Hz TMS, stratified by baseline ICF measures. The primary clinical outcome measure was the Children's Depression Rating Scale, Revised (CDRS-R). The CDRS-R and ICF biomarker were collected weekly. Forty-one participants received either 1 Hz (n = 22) or 10 Hz (n = 19) TMS treatments. CDRS-R scores improved compared to baseline in both 1 Hz and 10 Hz groups. For participants with low ICF at baseline, the overall least squares means of CDRS-R scores over the 6-week trial showed that depressive symptom severity was lower for the group treated with 1 Hz TMS than for those who received 10 Hz TMS. There were no significant changes in weekly ICF measurements across the 6 weeks of TMS treatment. Low ICF may reflect optimal glutamatergic N-methyl-d-aspartate (NMDA) receptor activity that facilitates the therapeutic effect of 1 Hz TMS through long-term depression-like mechanisms on synaptic plasticity. The stability of ICF suggests that it is a tonic, trait-like measure of NMDA receptor-mediated neurotransmission, with potential utility to inform parameter selection for therapeutic TMS in adolescents with MDD.

A Comparison of Cognitive Disengagement Syndrome in Children with Major Depression Versus Attention Deficit and Hyperactivity Disorder

Objective: There is growing evidence that Cognitive Disengagement Syndrome (CDS) is a distinct construct, supported by both empirical research and clinical differentiation. CDS demonstrates a stronger association with the inattentive type of Attention Deficit Hyperactivity Disorder (ADHD-IA), compared to its correlation with hyperactivity/impulsivity symptoms. Several studies have identified a significant positive relationship between CDS and internalizing symptoms such as anxiety and depression. To our knowledge, no study has explored CDS in children with major depression (MD). In the present study, we compared children with MD but without ADHD to children with ADHD but without depression in terms of CDS. We examined whether children with MD would have greater CDS when compared to children with ADHD. Methods: Thirty-six adolescents with ADHD, and twenty-five adolescents with MD, aged 12 to 18 years old, were administered the Barkley Child Attention Scale (BCAS), Turgay's DSM-IV Based ADHD and Disruptive Behavior Disorders Screening Scale, and the Children’s Depression Rating Scale-Revised (CDRS-R). Results: The majority of the ADHD and MD groups were boys. The MD group had significantly higher BCAS scores than the ADHD group (U=287.0, p=0.016). In the ADHD group, the severity of BCAS scores was inversely correlated with ADHD-Hyperactivity/impulsivity scores (r=-0.681, p<0.001). In the MD group, there was a significant positive relationship between BCAS and CDRS scores (r= 0.493, p=0.012). Conclusions: The findings of this study highlight the transdiagnostic relevance of CDS by demonstrating its association with depression, independent of ADHD. This underscores the importance of considering CDS in the assessment and treatment of depression across various clinical contexts.

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.

Deep transcranial magnetic stimulation for adolescents with treatment-resistant depression: A preliminary dose-finding study exploring safety and clinical effectiveness

BackgroundTranscranial magnetic stimulation (TMS) is an intervention for treatment-resistant depression (TRD) that modulates neural activity. Deep TMS (dTMS) can target not only cortical but also deeper limbic structures implicated in depression. Although TMS has demonstrated safety in adolescents, dTMS has yet to be applied to adolescent TRD. Objective/hypothesisThis pilot study evaluated the safety, tolerability, and clinical effects of dTMS in adolescents with TRD. We hypothesized dTMS would be safe, tolerable, and efficacious for adolescent TRD. Methods15 adolescents with TRD (Age, years: M = 16.4, SD = 1.42) completed a six-week daily dTMS protocol targeting the left dorsolateral prefrontal cortex (BrainsWay H1 coil, 30 sessions, 10 Hz, 3.6 s train duration, 20s inter-train interval, 55 trains; 1980 total pulses per session, 80 % to 120 % of motor threshold). Participants completed clinical, safety, and neurocognitive assessments before and after treatment. The primary outcome was depression symptom severity measured by the Children's Depression Rating Scale-Revised (CDRS-R). Results14 out of 15 participants completed the dTMS treatments. One participant experienced a convulsive syncope; the other participants only experienced mild side effects (e.g., headaches). There were no serious adverse events and minimal to no change in cognitive performance. Depression symptom severity significantly improved pre- to post-treatment and decreased to a clinically significant degree after 10 treatment sessions. Six participants met criteria for treatment response. LimitationsMain limitations include a small sample size and open-label design. ConclusionsThese findings provide preliminary evidence that dTMS may be tolerable and associated with clinical improvement in adolescent TRD.

Iron status in Swiss adolescents with paediatric major depressive disorder and healthy controls: a matched case–control study

PurposeDepression is associated with low-grade systemic inflammation and impaired intestinal function, both of which may reduce dietary iron absorption. Low iron status has been associated with depression in adults and adolescents. In Swiss adolescents, we determined the associations between paediatric major depressive disorder (pMDD), inflammation, intestinal permeability and iron status.MethodsThis is a matched case–control study in 95 adolescents with diagnosed pMDD and 95 healthy controls aged 13–17 years. We assessed depression severity using the Children’s Depression Rating Scale-Revised. We measured iron status (serum ferritin (SF) and soluble transferrin receptor (sTfR)), inflammation (C-reactive protein (CRP) and alpha-1-acid-glycoprotein (AGP)), and intestinal permeability (intestinal fatty acid binding protein (I-FABP)). We assessed history of ID diagnosis and treatment with a self-reported questionnaire.ResultsSF concentrations did not differ between adolescents with pMDD (median (IQR) SF: 31.2 (20.2, 57.0) μg/L) and controls (32.5 (22.6, 48.3) μg/L, p = 0.4). sTfR was lower among cases than controls (4.50 (4.00, 5.50) mg/L vs 5.20 (4.75, 6.10) mg/L, p < 0.001). CRP, AGP and I-FABP were higher among cases than controls (CRP: 0.16 (0.03, 0.43) mg/L vs 0.04 (0.02, 0.30) mg/L, p = 0.003; AGP: 0.57 (0.44, 0.70) g/L vs 0.52 (0.41, 0.67) g/L, p = 0.024); I-FABP: 307 (17, 515) pg/mL vs 232 (163, 357) pg/mL, p = 0.047). Of cases, 44% reported having a history of ID diagnosis compared to 26% among controls (p = 0.020). Finally, 28% of cases had iron treatment at/close to study inclusion compared to 14% among controls.ConclusionCases had significantly higher systemic inflammation and intestinal permeability than controls but did not have lower iron status. Whether this is related to the higher rate of ID diagnosis and iron treatment in adolescents with depression is uncertain.

Personality traits predict treatment outcome of an antidepressant in untreated adolescents with depression: An 8-week, open-label, flexible-dose study

BackgroundAntidepressant response in adults with major depressive disorder (MDD) is probably influenced by personality dimensions. However, personality dimensions in depression and their association with antidepressant treatment in adolescents are relatively unknown. We sought to investigate whether personality traits (PTs) can influence antidepressant treatment response in adolescents with depression. MethodsEighty-two adolescents with MDD who had completed the 8 weeks of treatment with selective serotonin reuptake inhibitors (SSRI) were enrolled. The Revised NEO Five-Factor Inventory (NEO-FFI-R) was used to measure their personality at baseline, and the 17-item Hamilton Depression Rating Scale (HAMD-17) and Children's Depression Rating Scale-Revised (CDRS-R) were used to evaluate depressive symptoms at baseline and 8 weeks. Moreover, logistic regression was performed to investigate the relationship between personality dimensions and antidepressant response. Receiver operating characteristic analyses were employed to determine the accuracy of a PT-based model in predicting the antidepressant response rate. ResultsAdolescents with MDD had significantly different PTs at baseline. Multivariable logistic regression analysis showed that extroversion scores were associated with response to antidepressant treatment, the lower the extroversion score, the better the response to antidepressant treatment, after correcting for variables with significant differences and trends or all potential confounding variables. It was also found that the combination of disease duration, extraversion-gregariousness, and agreeableness-trust effectively predicted antidepressant response in adolescents with MDD, with a sensitivity of 79.4 % and specificity of 68.7 %. ConclusionPersonality dysfunction in adolescents is associated with MDD. The antidepressant treatment response is influenced by the degree of extroversion in adolescents with MDD.

Abnormal Serum BDNF and p-mTOR in MDD in Adolescents with Childhood Trauma.

Adolescents with major depressive (MDD) episodes associated with childhood trauma have a poorer response to treatment and a higher risk of suicide. The underlying etiology is unclear. Brain-derived neurotrophic factor (BDNF) could improve depressive symptoms by down-regulating mammalian target of rapamycin (mTOR) signaling pathways, which was involved in adverse environmental stimuli during neurodevelopment. BDNF and mTOR have not been reported simultaneously in adolescents with major depressive episodes associated with childhood trauma. Childhood Trauma Questionnaire-Short Form (CTQ-SF), Children's Depression Inventory (CDI) and Children's Depression Rating Scale-Revised (CDRS-R) were used to evaluate the recruited adolescents with major depression episodes. Serum BDNF and p-mTOR levels were measured by ELISA in 31 adolescents with major depression episodes with childhood trauma and 18 matched healthy control. The serum levels of BDNF were significantly lower (p<0.001); and the serum levels of p-mTOR were high (p=0.003) in the adolescents with the first episode of major depressive episode accompanied by childhood trauma. Of the 31 adolescents with major depressive episodes, 17 had suicide or self-injury. Compared with the healthy control group, the serum levels of BDNF in patients with suicide or self-injury were lower than those without suicide or self-injury(p<0.001); the serum levels of p-mTOR were higher than those without suicide or self-injury (p=0.01). While in patients without suicide or self-injury, only serum p-mTOR was significantly higher than that in healthy group (p=0.028).BDNF was negatively correlated with CDRS-R (r=-0.427, p=0.006), p-mTOR was positively correlated with CDI (r=0.364, p=0.048). According to Receiver Operating Characteristic Curve (ROC), the combination of serum BDNF and p-mTOR levels have better diagnostic value. Neurotrophic and signaling pathways, involving BDNF and p-mTOR, may play a role in adolescent MDD with a history of childhood trauma, especially patients with suicide and self-injury tendencies.

Treatment guesses in the Treatment for Adolescents with Depression Study: Accuracy, unblinding and influence on outcomes.

We evaluated the presence and impact of unblinding during the influential Treatment for Adolescents with Depression Study (ClinicalTrials.gov Identifier: NCT00006286). Our analysis was part of a Restoring Invisible and Abandoned Trials reanalysis. Treatment for Adolescents with Depression Study trialled fluoxetine, placebo, cognitive behaviour therapy or their combination, in treating adolescents with major depressive disorder. We analysed the accuracy of guesses of fluoxetine or placebo allocation, and their effects on change in Children's Depression Rating Scale-Revised at 12 weeks. Of 221 participants allocated to fluoxetine or placebo, 151 adolescents (68%) had their guess about pill-treatment-arm allocation recorded at week 6, and guesses were recorded for 154 independent evaluators, 159 parents and 164 pharmacotherapists. All of these groups guessed treatment allocation more accurately than would be expected by chance (60-66% accuracy; all p-values ⩽ 0.004). Guesses did not become more accurate between 6 and 12 weeks and were not predicted by adverse events, though event documentation was poor. Treatment guess had a substantial and statistically significant effect on outcome (Children's Depression Rating Scale-Revised change mean difference 9.12 [4.69; 13.55], β = 0.334, p < 0.001), but actual treatment arm did not (1.53 [-2.83; 5.89], β = 0.056, p = 0.489). Removing guess from the analysis increased the apparent effect of treatment arm, making it almost statistically significant at the conventional alpha-level of 0.05 (p = 0.06). For Treatment for Adolescents with Depression Study, treatment guesses strongly predicted outcomes and may have led to the exaggeration of drug effectiveness in the absence of actual effects. The integrity of double-blinding in trials should be routinely assessed and reported.

Sequenced treatment alternatives to relieve adolescent depression (STAR-AD): a multicentre open-label randomized controlled trial protocol

BackgroundAdolescent major depressive disorder (MDD) is a prevalent mental health problem with low treatment success rates. Whether fluoxetine or fluoxetine combined with cognitive-behavioural therapy (CBT) is the more effective initial treatment for adolescent MDD remains controversial, and few studies have investigated whether treatment switching or augmentation is preferred when the initial treatment is not working well.MethodsWe developed a multicentre open-label Sequential Multiple Assignment Randomized Trial (SMART) design, consisting of two phases lasting 8 weeks each. In phase 1 (at baseline), patients will be recruited and grouped in fluoxetine group or fluoxetine combined with CBT group by patient self-selection. In phase 2 (after 8 weeks of treatment), the nonresponders will be randomly assigned to six groups, in which participants will switch to sertraline, vortioxetine, or duloxetine or added aripiprazole, olanzapine, or lithium carbonate to fluoxetine. After the full 16 weeks of treatment, we will assess the long-term sustainability of the treatment effects by evaluating participants during their subsequent naturalistic treatment. The primary outcome will be the response rate, determined by the Children’s Depression Rating Scale-Revised (CDRS-R). Secondary outcomes include the change in scores on the Beck Depression Inventory (BDI), the Screen for Child Anxiety-Related Emotional Disorders (SCARED) and the Safe Assessment.DiscussionThe results from this study will aid clinicians in making informed treatment selection decisions for adolescents with MDD.Trial registrationThis protocol was registered at ClinicalTrials.gov with Identifier: NCT05814640.

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.

Measures of Connectivity and Dorsolateral Prefrontal Cortex Volumes and Depressive Symptoms Following Treatment With Selective Serotonin Reuptake Inhibitors in Adolescents

Selective serotonin reuptake inhibitors (SSRIs) are considered a first-line pharmacological treatment for adolescent depression with moderate or higher levels of symptom severity. Thus, it is important to understand neurobiological changes related to SSRIs during the course of treatment for adolescents with depression. To examine neurobiological changes associated with SSRI treatment in adolescents with major depressive disorder (MDD) by measuring longitudinal changes in volume and resting-state functional connectivity (rsFC) in the dorsolateral prefrontal cortex (DLPFC), a core region of cognitive control. This cohort study was conducted with an open-label design. Adolescents with MDD and healthy controls were recruited at the Seoul National University Hospital (Seoul, South Korea). Adolescents with MDD were treated with escitalopram for 8 weeks. Data analysis was conducted between April 2021 and February 2022. Depressive symptoms were assessed using the Children's Depression Rating Scale-Revised. The outcome measure was defined as the change in Children's Depression Rating Scale-Revised scores from week 0 (before treatment) to week 8 (after treatment) or upon termination. Participants completed structural and resting-state functional magnetic resonance imaging (rsfMRI) assessments before (week 0) and after (week 8) SSRI treatment. Repeated measures analysis of variance and liner mixed model analyses were used to examine the longitudinal associations of SSRI treatment with DLPFC volume and rsFC between responders who showed at least a 40% decrease in depressive symptoms and nonresponders who did not. Ninety-five adolescents with MDD and 57 healthy controls were initially recruited. The final analyses of volume included 36 responders (mean [SD] age, 15.0 [1.6] years; 25 girls [69.4%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). Analyses of rsFC included 33 responders (mean [SD] age, 15.2 [1.5] years; 21 girls [63.6%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). The longitudinal associations of SSRI treatment were more evident in responders than in nonresponders. Responders showed significantly increased right DLPFC volume, decreased bilateral DLPFC rsFC with the superior frontal gyri, and decreased left DLPFC rsFC with the ventromedial PFC after treatment compared with before treatment. Furthermore, increased right DLPFC volume was correlated with decreased rsFC between the right DLPFC and superior frontal gyri after SSRI treatment. The preliminary results of this cohort study suggest that the DLPFC volumetric and rsFC changes may serve as potential neurobiological treatment markers that are associated with symptom improvement in adolescents with MDD.

Associations of n-3 polyunsaturated fatty acid status and intake with paediatric major depressive disorder in Swiss adolescents: A case-control study

BackgroundObservational studies suggest a link between n-3 polyunsaturated fatty acid (PUFA) intake, n-3 PUFA status, and depression in adults, but studies in adolescents are scarce. This study aimed to determine associations of n-3 PUFA status and intake with paediatric major depressive disorder (pMDD) in Swiss adolescents. MethodsWe conducted a matched case-control study in 95 adolescents diagnosed with pMDD and 95 healthy controls aged 13 to <18 years. We analysed red blood cell (RBC) fatty acid (FA) composition (% of total FA). n-3 PUFA intake was assessed using a focused food frequency questionnaire and depression severity was assessed by the Children's Depression Rating Scale-Revised (CDRS-R). ResultsMean RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were lower in cases than controls (EPA: 0.41 ± 0.11 vs 0.46 ± 0.12, p < 0.001; DHA: 4.07 ± 1.04 vs 4.73 ± 1.04, p < 0.001). Subsequently, the mean RBC n-3 index was lower (4.51 ± 1.10 vs 5.20 ± 1.11, p < 0.001) and the n-6/n-3 PUFA ratio higher (5.51 ± 1.25 vs 4.96 ± 1.08, p < 0.001) in cases than controls. Adolescents with a higher n-3 index had lower odds for depression (OR = 0.49 [95% CI: 0.32–0.71]). In contrast, the n-6/n-3 PUFA ratio was associated with higher odds for depression (OR = 1.58 [95% CI: 1.14–2.25]). Intake of alpha-linolenic acid, EPA and DHA did not differ between cases and controls. ConclusionOur results suggest that a higher RBC n-3 PUFA status during adolescence is associated with a lower risk for pMDD, whereas a higher n-6/n-3 PUFA ratio is associated with a higher risk for pMDD. Differences in n-3 PUFA intake did not explain the observed differences in n-3 PUFA status.

Prediction of Diagnosis and Treatment Response in Adolescents With Depression by Using a Smartphone App and Deep Learning Approaches: Usability Study.

Lack of quantifiable biomarkers is a major obstacle in diagnosing and treating depression. In adolescents, increasing suicidality during antidepressant treatment further complicates the problem. We sought to evaluate digital biomarkers for the diagnosis and treatment response of depression in adolescents through a newly developed smartphone app. We developed the Smart Healthcare System for Teens At Risk for Depression and Suicide app for Android-based smartphones. This app passively collected data reflecting the social and behavioral activities of adolescents, such as their smartphone usage time, physical movement distance, and the number of phone calls and text messages during the study period. Our study consisted of 24 adolescents (mean age 15.4 [SD 1.4] years, 17 girls) with major depressive disorder (MDD) diagnosed with Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and 10 healthy controls (mean age 13.8 [SD 0.6] years, 5 girls). After 1 week's baseline data collection, adolescents with MDD were treated with escitalopram in an 8-week, open-label trial. Participants were monitored for 5 weeks, including the baseline data collection period. Their psychiatric status was measured every week. Depression severity was measured using the Children's Depression Rating Scale-Revised and Clinical Global Impressions-Severity. The Columbia Suicide Severity Rating Scale was administered in order to assess suicide severity. We applied the deep learning approach for the analysis of the data. Deep neural network was employed for diagnosis classification, and neural network with weighted fuzzy membership functions was used for feature selection. We could predict the diagnosis of depression with training accuracy of 96.3% and 3-fold validation accuracy of 77%. Of the 24 adolescents with MDD, 10 responded to antidepressant treatments. We predicted the treatment response of adolescents with MDD with training accuracy of 94.2% and 3-fold validation accuracy of 76%. Adolescents with MDD tended to move longer distances and use smartphones for longer periods of time compared to controls. The deep learning analysis showed that smartphone usage time was the most important feature in distinguishing adolescents with MDD from controls. Prominent differences were not observed in the pattern of each feature between the treatment responders and nonresponders. The deep learning analysis revealed that the total length of calls received as the most important feature predicting antidepressant response in adolescents with MDD. Our smartphone app demonstrated preliminary evidence of predicting diagnosis and treatment response in depressed adolescents. This is the first study to predict the treatment response of adolescents with MDD by examining smartphone-based objective data with deep learning approaches.

The Quick Inventory of Depressive Symptomatology, Adolescent Version (QIDS-A17): A Psychometric Evaluation.

The current study aimed to evaluate the psychometric features of the Quick Inventory of Depressive Symptomatology, Adolescent version (QIDS-A17) and the clinician-rated Children's Depression Rating Scale-Revised (CDRS-R). Altogether, 103 outpatients (8 to 17 years) completed the self-report QIDS-A17-SR. Clinician interviews of adolescents (QIDS-A17-C (Adolescent)) and of parents (QIDS-A17-C (Parent)) were combined to create the QIDS-A17-C(Composite) and the CDRS-R. All QIDS-A17 measures and the CDRS-R evidenced high total score correlations and internal consistency. Factor analysis found all four measures to be unidimensional. Item Response Theory (IRT) analysis found results that complemented the reliability results found in CTT. All four also demonstrated discriminant diagnostic validity based on logistic regression and ANOVA analyses. The psychometric properties of the self-report and composite versions of the QIDS-A17 suggest acceptability as a measure of depression in adolescents either as a measure of depressive symptoms or severity of illness in adolescents. The self-report version may be a helpful tool in busy clinical practices.

Efficacy and Safety of Lurasidone in a Younger Population With Bipolar Depression: Pooled Post-hoc Analysis of Two Placebo-controlled Studies

AbstractIntroductionEarly onset of bipolar disorder is associated with high rates of psychiatric comorbidity (e.g., anxiety disorders, ADHD, PTSD), high rates of recurrence, and marked impairment in functioning and quality of life. The aim of this analysis was to evaluate the efficacy and safety of lurasidone in bipolar depression in youth and young adult patients (10–30 years old).MethodsData from two 6-week, double-blind, placebo-controlled studies of lurasidone monotherapy for bipolar I depression were pooled for this analysis. In the 1st study, patients 10–17 years old were evaluated using the Children’s Depression Rating Scale–Revised (CDRS-R) and the Clinical Global Impression-Bipolar Severity (CGI-BP-S) depression scale; in the 2nd study, a subgroup of adult patients (18–30 years old) were evaluated by CGI-BP-A, and the MADRS, with the latter being converted to a CDRS-R scores using a validated conversion algorithm.ResultsThe safety population consisted of 465 patients (mean age, 17.1 years; mean age of onset, 14.1; mean CDRS-R total score, 60.8). 400 patients (85.7%) completed the study. For lurasidone vs. placebo, LS mean Week 6 change was -21.4 vs. -15.3 for the CDRS-R total score (P&lt;0.0001; ES, 0.46); and -1.6 vs. -1.1 for the CGI-BP-S score (P&lt;0.0001; ES, 0.50). Adverse events (≥5%) on lurasidone vs. placebo were nausea (15.9% vs. 5.2%), headache (15.1% vs. 13.1%), somnolence (7.9% vs. 3.8%), vomiting (5.2% vs. 3.3%), and weight increase (5.2% vs. 2.3%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin.ConclusionsIn this post-hoc analysis of two placebo-controlled trials, lurasidone demonstrated clinically meaningful improvement of depressive symptoms in youth and young adults with bipolar depression. Lurasidone was generally safe, well-tolerated, and associated with minimal effects on weight, metabolic parameters, and prolactin.FundingServier Laboratories (Aust.) Pty. Ltd., and Sunovion Pharmaceuticals Inc.

Clinical effectiveness of training for awareness, resilience, and action for adolescents and young adults with depression: The pilot phase of a multicenter randomized controlled trial.

Depression is a top-ranking global health concern increasing in magnitude. Available treatments for adolescents and young adults are not convincingly effective and relapse rates remain high. Training for Awareness, Resilience and Action (TARA) is a group treatment program targeting specific pathophysiological mechanisms of depression in young people. TARA is feasible, acceptable, preliminarily efficacious in depressed American adolescents, and it affects postulated brain-circuitry. As an initial step of a multicenter randomized controlled trial (RCT) we performed a single-arm multicenter pilot-study on TARA. Thirty-five depressed individuals (15-21 years old, 28 females) received TARA for 12 weeks face-to-face or online. Data was collected before (T0), during, and after the intervention (T1). The trial was pre-registered at clinicaltrials.gov, NCT Registration: identifier [NCT04747340]. Feasibility outcomes included recruitment, attendance rates, and session ratings. Adverse events were recorded weekly and extracted from medical records at the end of the trial. Primary effectiveness outcome was self-rated depression severity on Reynolds Adolescent Depression scale 2nd ed. at T1. Secondary outcomes were Children's Depression Rating Scale-revised (CDRS-R) and Multidimensional Anxiety Scale for Children (MASC) at T1. TARA was feasible and safe in the present trial. No significant RADS-2-change was seen (adjusted mean difference -3.26, 95 % CI -8.35 to 1.83; p= 0.20), however a significant decrease in CDRS-R scores is reported (adjusted mean difference -9.99, 95% CI -14.76 to -5.22; p < 0.001). MASC-scores did not change significantly (adjusted mean difference 1.98, 95% CI -0.96 to 4.91; p=0.18). Additional feasibility aspects are presented and discussed. Limitations include substantial loss-to-follow-up, no randomization to control, and that some participants received concomitant treatment(s). The Coronavirus pandemic complicated both implementation and interpretation of the trial. In conclusion TARA was feasible and safe in depressed adolescents and young adults. Preliminary signs of effectiveness were seen. The initiated RCT will be important and worthwhile to conduct, and several improvements to the design are suggested based on the present results. clinicaltrials.gov, identifier NCT04747340.

Early reduction in irritability is associated with improved outcomes among youth with depression: Findings from the AMOD study

ObjectivesEvaluate whether early improvement in irritability predicts improvement in depression severity in a naturalistic sample of adolescents undergoing pharmacologic treatment for major depressive disorder. MethodsAdolescents (N = 161) aged 13–18 years with a moderate to severe depressive episode were enrolled. Outcome measures included the Children's Depression Rating Scale-Revised (CDRS-R), Quick Inventory of Depressive Symptomatology (QIDS-A17), and Clinical Global Impression scale (CGI). Paired t-tests were used to estimate the change in irritability items from baseline to week-4, and Cohen's d effect sizes were computed. Separate linear regression analyses with CDRS-R, QIDS-A17, and CGI at week-8 as the dependent variables and baseline levels of irritability and baseline-to-week-4 changes in irritability as independent variables of interest were conducted. These analyses were repeated after controlling for overall depression severity (minus the irritability item) at baseline and baseline to week-4 change. ResultsGreater baseline to week-4 reduction in irritability was associated with lower levels of CDRS-R, QIDS-A17, and CGI at week-8. These findings were significant for QIDS-A17 and CGI even after controlling for baseline-to-week-4 changes in other depressive symptoms. LimitationsThe single item evaluation of irritability reduced assessment reliability in the absence of validated measures of irritability. ConclusionsEarly reduction in irritability is strongly associated with better outcomes in depressed youths, regardless of baseline depression severity. Further research is needed to quantify the burden of irritability, explore it as a tool for measurement-based care, and to develop targeted treatments for irritability.

2.55 Positive Predictive Factors of Transcranial Magnetic Stimulation Efficacy in the Treatment of MDD in Adolescents

2.55 Positive Predictive Factors of Transcranial Magnetic Stimulation Efficacy in the Treatment of MDD in Adolescents

Efficacy and safety of repetitive transcranial magnetic stimulation in children and adolescents with depression: A systematic review and preliminary meta-analysis

BackgroundRepetitive transcranial magnetic stimulation (rTMS) benefits adults with depression while its efficacy and safety in children and adolescents with major depressive disorder (MDD) remain unclear. We conducted a preliminary meta-analysis here to objectively appraise rTMS in the youth with MDD to inform future research and clinical practice. MethodsWe searched Pubmed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials from their inception to December 1, 2021. Studies with a control group or self-controlled designs and evaluating the Hamilton Depression Scale (HAM-D) or the Children's Depression Rating Scale–Revised (CDRS-R) at baseline and post-rTMS treatment were included. Two reviewers independently selected eligible studies, retrieved data in a structured fashion and assessed studies' quality. Hedges'g with 95 % confidence intervals and withdrawal rate with 95 % confidential intervals were separately used to evaluate the efficacy and safety of rTMS. ResultsThirteen studies with six datasets (165 patients, 61.8 % female, age range from 10 to 25 years old) were included and our meta-analysis found children and adolescents with MDD benefited from rTMS treatment (Hedges'g 1.37, 95 % CI 0.85 to 1.90, P = 0.001). In addition, 4 % of patients (95 % CI 0.02 to 0.09) withdrew during rTMS treatment for reasons including fear, mood swings, suicide ideation and adverse events. LimitationsThis conclusion is tempered by a small number of studies included and a potentially existing placebo effect. ConclusionsOur findings suggest rTMS could benefit children and adolescents with MDD in a relatively safe manner, and this result may help guide clinical practice.