Treatment For Adolescents With Depression Study Research Articles

Barriers to access to clinical trial data: Obstruction of a RIAT reanalysis of the treatment for adolescents with depression study.

Public access to data has been a major step in attempting to reduce bias in scientific literature. Data to verify efficacy outcomes are now more accessible; however, little has been done to ensure public access to harms data from RCTs, which are equally important in ascertaining possible misreporting and protecting safety. The treatment for adolescents with depression study (TADS) has influenced most international practice guidelines for treating children and adolescents with depression, supporting first-line prescription of fluoxetine in combination with cognitive behavioural therapy (CBT). However, after over 30 publications by the TADS team, reporting on harms remains highly deficient and we aimed to redress this lack. In undertaking a restoring invisible and abandoned trials (RIAT) reanalysis of TADS' effectiveness and safety outcomes, we sought access to de-identified serious adverse events (SAE) data. This paper describes our unsuccessful efforts to obtain more detailed SAE data from TADS' data custodians, highlighting several problematic blocks to comprehensive safety reporting. Comprehensive access to clinical trial data is necessary to ensure safe and fully informed guidelines for treating children and adolescents with depression.

Moderators and Predictors of Response After 36 Weeks of Treatment in the Treatment for Adolescents with Depression Study (TADS).

This study investigated pretreatment variables associated with depression severity in adolescents following maintenance treatment for major depressive disorder (MDD). Data was derived from the Treatment for Adolescents with Depression Study (TADS). Participants received one of three treatments: cognitive behavioral therapy (CBT), fluoxetine (FLX), or combined CBT and fluoxetine (COMB). Participants received 12weeks of acute treatment, 6weeks of consolidation treatment, and 18weeks of maintenance treatment (N = 327, Mage = 14.62 yrs). Outcome was measured by the Children's Depression Rating Scale-Revised. Results showed adolescents with shorter depressive episodes, better global functioning, less suicidal ideation, better health/social functioning, and greater expectancy of positive treatment response were more likely to have lower depression severity following 36weeks of treatment, regardless of modality. Adolescents with lower initial depression demonstrated lower depression severityif treated with CBT. FLX was more effective in reducing depression severity in adolescents with severe baseline depression than for those with mild or moderate depression. Adolescents with higher family incomes were more likely to have lower depression severity if they received CBT only. In conclusion,adolescents with shorter depressive episodes, better health, social, and global functioning, less suicidal ideation, and greater expectancy for treatment at baseline respond equally well to CBT, fluoxetine, and combined treatment. Adolescents who are more severely depressed at baseline may have a better treatment response if they are treated with FLX; whereas adolescents of higher income are more likely to have a better response if they receive CBT only.

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.

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.

Marital and Parent-Child Relationships during Treatment for Adolescent Depression: Child-Driven and Bidirectional Effects.

Adolescent depression can be a stressor for parents and families. This study evaluated how treating adolescent depression affects marital and parent-child relationships. We examined whether marital adjustment and parent-child conflict improved over the course of active treatment of depressed adolescents (36-week visit) and long-term follow-up (one year after discontinuation of treatment) in a sample of 322 clinically depressed youth participating in the Treatment for Adolescents with Depression Study (TADS). We also explored the bidirectional influences of adolescent depression and family relationships. Results indicated that marital adjustment was stable during active treatment but declined during long-term follow up. A structural equation model (SEM) examining the bidirectional relation between adolescent depression and marital adjustment indicated that higher adolescent depression at the conclusion of maintenance treatment (24-week visit) predicted a deterioration of marital adjustment at the end of active treatment (36-week visit). Parent-child conflict was unchanged during treatment and follow up. SEM analyses examining the bidirectional relationship between youth depression and parent-child conflict revealed that reduced depressive symptoms at the end of the active treatment period predicted improvement in parent-child conflict at subsequent time points. These findings suggest that youth depression and its treatment may influence long-term family functioning.

Critical appraisal of adverse effects reporting in the ‘Treatment for Adolescents With Depression Study (TADS)’

ObjectiveTo identify all publications from the ‘Treatment for Adolescents With Depression Study (TADS)’ and assess the findings regarding occurrence of any adverse effects in the treatment groups both for the...

More on TADS: What works for whom in adolescent depression treatment

Adolescents with depression can be divided into three unique classes: those with high severity with early significant improvement, those with high severity with limited symptom change, and those with moderate severity with late significant improvement, according to researchers who analyzed recent results of the Treatment for Adolescents with Depression Study (TADS). Baseline predictors of which class a child would end up in include treatment condition, gender, age, stage of change, depression severity, number of comorbid disorders, hopelessness, melancholia, suicidality, and cognitive distortions. The study results have implications for what kind of treatment to use for depressed adolescents.

Treatment for Depression Enhances Protection: Findings From the Treatment for Adolescents With Depression Study (TADS)

The Treatment for Adolescents With Depression Study (TADS) evaluates the effectiveness of fluoxetine, CBT, and their combination relative to placebo in adolescents with MDD. This report examines treatment influences on protective factors: self-concept and problem-solving skills (individual domain), and family connectedness, parent–child relations, and parental support (family domain). Protective factors were measured prior to treatment, and after 12 and 36 weeks of treatment. Nearly all protective factors improved with treatment. Treatment groups differed in their impact on protective factors. Combined treatment generally outperformed all other groups. CBT enhanced problem-solving skills more than fluoxetine. Fluoxetine enhanced parents’ perceptions of parent–child relations by 12 weeks. CBT raised adolescents’ perceptions of family connectedness by 36 weeks. CBT has a unique impact on problem-solving ability. Parent and adolescent perceptions of family domain protective factors differ, in that parent per...

A Primate Model of the Effects of Childhood Antidepressant Treatment

A Primate Model of the Effects of Childhood Antidepressant Treatment

Increasing Positive Outlook Partially Mediates the Effect of Empirically Supported Treatments on Depression Symptoms Among Adolescents

Among adolescents there is evidence that cognitive change partially mediates the effect of cognitive behavioral therapy (CBT) on depression outcome. However, prior studies have been limited by small samples, narrow measures of cognition, and failure to compare cognitive change following CBT to cognitive change following antidepressant medication. This study examined whether change in four cognitive constructs (cognitive distortions, cognitive avoidance, positive outlook, and solution-focused thinking) mediated change in depression severity in a sample of 291 adolescents who participated in the Treatment for Adolescents with Depression Study (TADS). TADS assessed the effects of CBT, fluoxetine, and their combination on depression severity. All three treatments were associated with change in the cognitive constructs and combination treatment produced the greatest change. Furthermore, change in the cognitive constructs partially mediated change in depression severity within all three treatments. Results implicated positive outlook as the construct most associated with change in depression severity over 36 weeks.

Antidepressants for children with depression.

The Forum about treating depressed children presented in the previous issue of the journal[1],[2] highlighted several important issues about this controversial topic. Depression in children is a devastating disorder that effects psychosocial development and has long-term negative outcomes for both the patients and their families.[3]-[5] It has a relatively high prevalence of 1 to 2% in children and 3 to 8% in adolescents[3], but there are few randomized controlled trials on the efficacy of pharmacotherapy and other treatments for the disorder.[3]-[9] After the FDA's ‘black box’ warning about the potential suicide risk of antidepressant use in children in 2004, the diagnosis of pediatric depression in the United States decreased from 5 per 1000 managed care enrollees to 3 per 1000 and the prescription of antidepressants among treatment-naive patients with depression who were 5 to 21 years of age decreased by approximately 50%.[6] These changes following the FDA warning suggest that many children with depression were not being treated with appropriate medication. This hypothesis is supported by the increase in the suicide rates of children and adolescents – by 14% in the United States[10] and 25% in Canada[6]—in the years following the FDA warning compared to increasing antidepressant prescription use and a decline in suicide rates among children and youth in the years prior to the warning.[6],[7] The results of several reviews about the association between the treatment of pediatric depression with antidepressants and suicidality have questioned the appropriateness of the FDA warning.[5]-[11] Ecological studies have reported a beneficial effect of antidepressant prescription in children and adolescents. In the United States, suicide rates among children and adolescents decreased from 4.4 per 100,000 to 2.8 per 100,000 between 1999 and 2003, a period during which there was a substantial increase in the rates of prescription of selective serotonin reuptake inhibitor (SSRI) antidepressants for pediatric depression.[6] The Treatment for Adolescents with Depression Study (TADS) found that adolescents with major depressive disorder (MDD) show significant decreases in suicidality in all treatment arms but no significant difference in between those treated with fluoxetine and those treated with CBT.[12] More recent studies also indicate that antidepressants are modestly effective for the treatment of pediatric MDD and that the benefits outweigh the risks of suicidalilty.[11] Finally, the FDA's warning applied to all antidepressants, but it appears that the relationship between antidepressant use and suicidality in children and adolescents varies for the different types of antidepressants.[4] Despite the limited number of randomized controlled trials of pharmacotherapy for children with depressive disorders and the inconsistency of the results,[5] several studies found that SSRIs were significantly superior to placebo.[5],[6],[9]-[11] But some studies report antidepressants of limited use in children with depression.[9] Psychotherapy, especially CBT, and manipulation of the psychosocial context (including treatment of parental psychopathology) is considered effective for most children with mild or moderate depression,[7],[10] but usually needs to be augmented with antidepressants in those with severe depression.[9] Based on scientific reviews and expert consensus statements, several practice guidelines recommend using fluoxetine or escitalopram – both of which are approved by the FDA – as the first-line pharmacological treatment for children and adolescents with MDD if medication is indicated.[5]-[11] With appropriate monitoring for suicidality and other potential adverse events, patients with severe forms of pediatric MDD or with less severe MDD that does not respond to psychosocial interventions alone will often benefit from combined psychosocial and psychopharmacological interventions.

Impact of Childhood Trauma on Treatment Outcome in the Treatment for Adolescents with Depression Study (TADS)

Impact of Childhood Trauma on Treatment Outcome in the Treatment for Adolescents with Depression Study (TADS)

Parental Marital Discord and Treatment Response in Depressed Adolescents

Evidence suggests that parental marital discord contributes to the development of internalizing and externalizing symptoms in children and adolescents. Few studies, however, have examined the association between parental marital discord and youth's response to treatment. The present study examined the impact of interparental discord on treatment response in a randomized control trial of adolescents with major depression enrolled in the Treatment for Adolescents with Depression Study (TADS). Participants were 260 adolescents from two-parent households randomly assigned to one of four treatment groups: fluoxetine (FLX), cognitive behavior therapy (CBT), their combination (COMB), or placebo (PBO). Logistic regressions revealed that parental marital discord interacted with youth gender and co-morbid oppositionality symptoms to predict group differences in treatment response.

The need for a long-term perspective in child and adolescent psychiatry

When taking care of our patients and families in daily clinical practice, it is difficult to not solely be directed at acute, short-term improvements. Typically, patients are being referred to our clinical services at a time when symptoms of mental disorders have already led to significant impairments on important areas such as social, academic, and family functioning. Then, obviously, we try to put effective interventions in place that aim to decrease symptoms as well as reduce impairments. Indeed, we now have several treatments in the field of child and adolescent psychiatry with a solid evidence base [1]. Well-researched examples include the use of stimulant medications for attention-deficit/hyperactivity disorder (ADHD), risperidone [2] and aripiprazole [3] for irritability in autism spectrum disorders, and behavioral parent training [4] for children with disruptive behavior problems. Ideally, however, in addition to addressing the acute needs of our pediatric patients, our interventions should be truly aimed at preparing our children for a better life in the long run. Will the interventions we apply contribute to the better functioning of our patients as adults? The long-term results of the Multimodal Treatment study of ADHD (MTA) [5] have been complex, but clearly demonstrate that there is not a simple relationship between impressive acute treatment effects of well-monitored stimulant medication and effects over the long run. Fortunately, the Treatment for Adolescents with Depression Study (TADS) [6] that investigated the effectiveness of fluoxetine, cognitive-behavioral therapy, and their combination in adolescents with major depressive disorder was able to demonstrate persistent benefits of treatments over 1 year of naturalistic follow-up. This issue of European Child and Adolescent Psychiatry contains several articles that deal with the long-time perspective in our field. Gevensleben et al. [7] report on the long-term follow-up of their randomised controlled trial of neurofeedback versus a control treatment (a computerized attention skills training) in children with ADHD and demonstrated that behavioral improvements through neurofeedback were actually maintained at a 6-month follow-up. Longitudinal cohort studies are a classic way to investigate the long-term effects of important environmental factors for children’s development. Elberling et al. [8] longitudinally studied the influence of perinatal and socioeconomic data, and data on child mental illness diagnosed in preschool years on psychosocial function at 5–7-year follow-up, in the Copenhagen Child Cohort, which involves more than 6,000 children. Several markers of socioeconomic disadvantages were found to be associated with mental health problems at 5–7 years of age. In another large-scale longitudinal cohort study in Norway in this issue, Lien et al. [9] showed that internalizing mental health problems among adolescent girls were significantly associated with atopic conditions 3 years earlier, thus demonstrating that atopy may have long-lasting effects on mood and anxiety levels. Finally, a truly long-term perspective on our field is provided by a wonderful overview by the most eminent long-term leader and pioneer of child and adolescent psychiatry. Professor Sir Michael Rutter gives a unique perspective on the developments from the mid-twentieth century onwards, ending with a look ahead to the most important opportunities and challenges as well as the hazards that need to be avoided.

Extreme thinking in clinically depressed adolescents: Results from the Treatment for Adolescents with Depression Study (TADS)

The purpose of this report is to examine relations between extreme thinking, as measured by the Dysfunctional Attitudes Scale, and the maintenance of gains among adolescents who participated in the Treatment for Adolescents with Depression Study (TADS). We examine extreme thinking among 327 adolescents (mean age=14.56, 57% female, 75% White) who received cognitive behavior therapy (CBT), fluoxetine (FLX), or a combination of CBT and FLX (COMB). Among those who met remission status on the Children’s Depression Rating Scale – Revised (CDRS-R≤28; 56 at week 12, 79 at week 18) extreme thinking did not predict failure to maintain remission. This is in contrast to findings with depressed adults. Treatment influenced level of extreme thinking, and this appeared to be driven by greater endorsement of positively valenced beliefs as opposed to a decrease in negatively valenced beliefs. Developmental or investigation characteristics may account for the discrepancy in findings.

Ethnic differences among adolescents beginning treatment for depression.

This study examines ethnic/racial differences at the start of treatment among participants in the Treatment for Adolescents with Depression Study (TADS). African American and Latino youth were compared to Caucasian youth on symptom presentation and cognitive variables associated with depression. Contrary to hypothesis, there were no significant differences in symptom presentation as measured by the interview-based items of the Children's Depression Rating Scale--Revised (CDRS-R). However, African American and Latino youth were both rated as demonstrating more severe symptoms on the observational items of the CDRS-R compared to Caucasian youth. In terms of cognitive variables associated with depression, African Americans reported fewer negative cognitive biases compared to Caucasians, but cognitive biases were significantly correlated with depression severity across ethnic groups.

Impact of Childhood Trauma on Treatment Outcome in the Treatment for Adolescents with Depression Study (TADS)

The impact of childhood trauma was examined in 427 adolescents (54% girls, 74% Caucasian, mean = 14.6, SD = 1.5) with major depressive disorder participating in the Treatment for Adolescents with Depression Study (TADS).TADS compared the efficacy of cognitive behavioral therapy (CBT), fluoxetine (FLX), their combination (COMB), and placebo (PBO). Teens were separated into four trauma history groups: (1) no trauma; (2) trauma, no abuse; (3) physical abuse; (4), and sexual abuse. The effects of treatment and trauma history on depression severity across 12 weeks of acute treatment, as measured by the Children's Depression Rating Scale-Revised (CDRS-R), were examined.A significant trauma-by-treatment-by-time interaction indicated that trauma history moderated treatment. The Week 12 primary efficacy findings previously reported by TADS were replicated in the no trauma group (n = 201): COMB = FLX > CBT = PBO. No significant differences in treatment arms were observed among the trauma, no abuse, or physical abuse group. Teens with a history of sexual abuse treated with COMB, FLX, and PBO showed significant and equivalent improvement on the CDRS-R (mean <45), whereas the mean CDRS-R for the CBT group tended to remain in the depressed range (mean >45). Baseline suicidality and self-reported depression were significantly related to a history of sexual abuse.The study was limited by the level of detail regarding childhood traumatic experiences. Results are discussed in terms of the implications for treating depressed adolescents with traumatic backgrounds.Clinical Trials Registry Information: Treatment for Adolescents with Depression Study; http://www.clinicaltrials.gov, NCT00006286.

Impact of Childhood Trauma on Treatment Outcome in the Treatment for Adolescents with Depression Study (TADS)

The impact of childhood trauma was examined in 427 adolescents (54% girls, 74% Caucasian, mean = 14.6, SD = 1.5) with major depressive disorder participating in the Treatment for Adolescents with Depression Study (TADS). TADS compared the efficacy of cognitive behavioral therapy (CBT), fluoxetine (FLX), their combination (COMB), and placebo (PBO). Teens were separated into four trauma history groups: (1) no trauma; (2) trauma, no abuse; (3) physical abuse; (4), and sexual abuse. The effects of treatment and trauma history on depression severity across 12 weeks of acute treatment, as measured by the Children's Depression Rating Scale-Revised (CDRS-R), were examined. A significant trauma-by-treatment-by-time interaction indicated that trauma history moderated treatment. The Week 12 primary efficacy findings previously reported by TADS were replicated in the no trauma group (n = 201): COMB = FLX > CBT = PBO. No significant differences in treatment arms were observed among the trauma, no abuse, or physical abuse group. Teens with a history of sexual abuse treated with COMB, FLX, and PBO showed significant and equivalent improvement on the CDRS-R (mean <45), whereas the mean CDRS-R for the CBT group tended to remain in the depressed range (mean >45). Baseline suicidality and self-reported depression were significantly related to a history of sexual abuse. The study was limited by the level of detail regarding childhood traumatic experiences. Results are discussed in terms of the implications for treating depressed adolescents with traumatic backgrounds.Clinical Trials Registry Information: Treatment for Adolescents with Depression Study; http://www.clinicaltrials.gov, NCT00006286.

Findings From the Treatment for Adolescents with Depression Study (TADS): What Have We Learned? What Do We Need to Know?

This introduction to the special section on findings from the Treatment for Adolescents with Depression Study provides a review of the rationale for the study, its design, and principal findings to date. Findings with regard to acute effectiveness of alternative treatments, relapse, recurrence, maintenance of gains, and the effects of treatment on suicidal ideations and suicidal behavior are reviewed. We conclude with a brief discussion of unresolved clinical issues, including treatment resistance, management of partial response, moderators and predictors of long-term response, and mediators of clinical change. The articles of the special section address a range of issues including relations between cognitive factors associated with depression, relations between maladaptive beliefs and treatment response, cognitive mediators of therapeutic improvement, relations between family conflict and treatment response, and the economic costs of adolescent depression.

Dysfunctional Attitudes Scale Perfectionism: A Predictor and Partial Mediator of Acute Treatment Outcome among Clinically Depressed Adolescents

The effect of perfectionism on acute treatment outcomes was explored in a randomized controlled trial of 439 clinically depressed adolescents (12–17 years of age) enrolled in the Treatment for Adolescents with Depression Study (TADS) who received cognitive behavior therapy (CBT), fluoxetine, a combination of CBT and FLX, or pill placebo. Measures included the Children's Depression Rating Scale–Revised, the Suicidal Ideation Questionnaire–Grades 7–9, and the perfectionism subscale from the Dysfunctional Attitudes Scale (DAS). Predictor results indicate that adolescents with higher versus lower DAS perfectionism scores at baseline, regardless of treatment, continued to demonstrate elevated depression scores across the acute treatment period. In the case of suicidality, DAS perfectionism impeded improvement. Treatment outcomes were partially mediated by the change in DAS perfectionism across the 12-week period.