Comparative efficacy of cognitive behavioral therapy,fluoxetine, and their combination in depressed adolescents: Initial lessons from the treatment for adolescents with depression study

Adolescents with major depressive disorder (MDD), their families and clinicians experience significant challenges when weighing the potential risks versus benefits of available choices in the treatment of MDD. Although MDD is highly prevalent in adolescents and is associated with marked suffering, impairment and risk of suicide, the scientific data regarding the safety and efficacy of treatments for pediatric depression are limited. Controlled clinical trials have provided support for the use of psychotherapy and fluoxetine for the treatment of pediatric depression, but until recently no information on the comparative efficacy of these recommended interventions alone or in combination was available. The Treatment for Adolescents with Depression Study provides a very important therapeutic advance in the field by convincingly showing that combination treatment with cognitive behavioral therapy and fluoxetine has the best benefit to risk ratio for adolescents with moderate to severe depression, and is superior to monotherapy. Moreover, the study results confirm that fluoxetine alone is effective in the treatment of depressed adolescents.     

Addressing the Needs of Adolescents with Treatment Resistant Depressive Disorders: A Systematic Review of rTMS

BackgroundDepressive disorders are among the most commonly experienced mental health concerns and a leading cause of mortality in adolescence. Current treatment guidelines recommend the use of antidepressant medication, cognitive behavioral therapy or both treatments. Unfortunately 40–60% of adolescents fail to respond to these treatments, therefore a new effective alternative treatment modality would be of particular benefit. rTMS is effective in addressing treatment resistant depression in adults and investigation into its effectiveness with adolescent populations has begun.ObjectiveTo examine the existing literature regarding the efficacy and safety of rTMS treatment with adolescents experiencing depressive symptoms, especially research conducted since the last published review.MethodsA systematic review was conducted in accordance with PRISMA guidelines. The databases of OVID PsycINFO, PubMed, Ovid Medline and Web of Science were searched for research utilizing rTMS treatment with adolescents experiencing depressive symptomology.ResultsThe review identified seven studies that examined rTMS as a treatment for depressive symptomology in adolescence. Findings indicate rTMS is likely to be an effective treatment for young people with preliminary longitudinal results suggesting maintenance of effects 3 years post-treatment. Reported side effects have included headaches, scalp discomfort and single incidences of hypomania and seizure. All side effects were transitory and did not recur.ConclusionPreliminary results suggest rTMS is an effective and well tolerated antidepressant treatment for adolescents with treatment resistant depressive symptomology. Further research allowing for comparison across studies is necessary to establish the efficacy of rTMS in adolescent depression.     

Eye Movement Desensitization and Reprocessing for Adolescent Depression

While cognitive behavior therapy is considered to be the first-line therapy for adolescent depression, there are limited data on whether other psychotherapeutic techniques are also effective in treating adolescents with depression. This report suggests the potential application of eye movement desensitization and reprocessing (EMDR) for treatment of depressive disorder related, not to trauma, but to stressful life events. At present, EMDR has only been empirically validated for only trauma-related disorders such as posttraumatic stress disorder. Two teenagers with major depressive disorder (MDD) underwent three and seven sessions of EMDR aimed at memories of stressful life events. After treatment, their depressive symptoms decreased to the level of full remission, and the therapeutic gains were maintained after two and three months of follow up. The effectiveness of EMDR for depression is explained by the model of adaptive information processing. Given the powerful effects observed within a brief period of time, the authors suggest that further investigation of EMDR for depressive disorders is warranted.     

Child and adolescent depression: short-term treatment effectiveness and long-term opportunities

As with adult major depressive disorder (MDD), child and adolescent MDD is characterized as a common, chronic and recurrent disorder. It is also associated with short- and long-term functional impairment, morbidity, and mortality. Effective treatments, both psychotherapeutic and pharmacotherapeutic, are available for the short-term treatment and management of youth with MDD. However, to date, there are no data on the long-term treatment and management of children and adolescents with MDD and how long-term treatment may affect the outcomes of either high-risk or already affected youth. Understanding the long-term consequences of MDD during youth is as important as understanding how to treat a single episode of depression. Available data on the pharmacotherapeutic and psychotherapeutic options are discussed. In general, tricyclic antidepressants (TCAs) are not as effective for the treatment of youth with MDD as adults with MDD. The selective serotonin reuptake inhibitors (SSRIs) have been shown to be effective in children and adolescents with MDD and non-obsessive compulsive anxiety disorders. The serotonin and norepinephrine reuptake inhibitor (SNRI), venlafaxine XR, has been shown to be effective for the treatment of generalized anxiety disorder in children and adolescents. Understanding the long-term clinical consequences of depressive disorders in youth may provide opportunities for better intervention across the clinical course of illness. Early recognition, diagnosis and adequate treatment of 'high-risk' youth with subsyndromal depressive symptoms, treatment of acute episodes of depression to prevent 'kindling', and aggressive prophylaxis have the potential to improve the mental health of youth throughout their lives.     

Clinical case study: CBT for depression in a Puerto Rican adolescent: challenges and variability in treatment response

Background: There is ample evidence of the efficacy of cognitive‐behavioral therapy (CBT) for depression in adolescents, including Puerto Rican adolescents. However, there is still a high percentage of adolescents who do not respond to a standard “dose” of 12 sessions of CBT. This clinical case study explores the characteristics associated with treatment response in a Puerto Rican adolescent and illustrates the challenges and variability inherent in CBT treatment for major depressive disorder (MDD) in youth. Methods: The patient is a 15‐year‐old adolescent female who at pretreatment presented a diagnosis of MDD with severe depressive symptoms, high suicidal ideation, low self‐concept, and highly dysfunctional attitudes. CBT treatment consisted of 12 standard individual therapy sessions plus four additional sessions, and one family intervention. A case study method was used. Both qualitative and quantitative data for the case are presented using self‐report instruments, clinical case notes and recordings of therapy sessions. Results: Some of the characteristics she presented that have been associated with partial or no response to therapy were: increased severity of depressive symptoms, a prior MDD episode, co‐morbidity with other mental disorders, and significant parental conflict. At termination the patient presented decreases in depressive symptoms, dysfunctional attitudes, and suicidal ideation, as well as improvements in self‐concept. These improvements were maintained up to 1 year posttreatment. Conclusions: Cultural issues are discussed in terms of the potential for parental conflict to perpetuate the patient's depressive symptoms. Depression and Anxiety, 2009. © 2008 Wiley‐Liss, Inc.     

Paediatric major depressive disorder: neurobiology and implications for early intervention

Aim: Paediatric major depressive disorder (MDD) is associated with chronicity and poor outcomes. The goals of this review are (i) to integrate how developing biological systems contribute to the pathophysiology of paediatric MDD, and (ii) to consider the role of early intervention for depressed youth. Methods: A developmental perspective is applied herein to review and integrate key neurobiological systems that are implicated in paediatric MDD. We also review recent treatment research for adolescents with MDD. Results: Available evidence in paediatric and adult populations support an integrative model for the pathophysiology of MDD that involves fronto‐limbic neural circuitry and the neuroendocrine stress response system. Evidence from treatment research supports the efficacy of available treatments modalities, including antidepressant medications, cognitive behavioral therapy, and their combination, for the majority of adolescents with moderate to severe MDD. Conclusions: Since the biological systems implicated in MDD mature through adolescence, adolescents may be more susceptible to developing depression but also may be more amenable to treatment interventions. Early identification and treatment of paediatric MDD may be able to divert negative trajectories and lead to improved outcomes.     

Adolescent outpatients with depressive disorders: clinical characteristics and treatment received

Depressive disorders constitute a common clinical problem. However, research on psychosocial impairment and treatment-related factors among adolescent outpatients with different diagnoses of depression is scarce. This study aimed at investigating consecutively referred outpatient adolescents with depressive syndrome compared with psychiatric controls. We also compared those with major depression (MDD), other depressive disorders (OD), or adjustment disorder with depressed mood (ADDM) in terms of psychosocial impairment and treatment received in a sample of 302 consecutively referred adolescent outpatients. Psychosocial impairment was most severe in MDD. Comorbidity with anxiety disorders characterized those with MDD, whereas antisocial disorders were common among those with OD. Psychosocial treatment was more intensive and psychotropic medication more prevalent in patients with MDD compared with those with OD or ADDM. All the depressed patients receiving psychotropic medication had additional psychosocial treatments. Psychosocial functioning improved in all three groups (MDD, OD, ADDM), whether their treatment involved only psychotherapeutic treatments or additional psychotropic medication. Adolescents with different diagnoses of depression have specific psychosocial impairments that have to be taken into account in developing psychiatric treatments for them.     

Attachment-based family therapy for depressed adolescents: a treatment development study

OBJECTIVE: To design a treatment manual and adherence measure for attachment-based family therapy (ABFT) for adolescent depression and to collect pilot data on the treatment's efficacy. METHOD: Over a period of 2 years, 32 adolescents meeting criteria for major depressive disorder (MDD) were randomly assigned to 12 weeks of ABFT or a 6-week, minimal-contact, waitlist control group. The sample was 78% female and 69% African American; 69% were from low-income, inner-city communities. RESULTS: At post-treatment, 81% of the patients treated with ABFT no longer met criteria for MDD, in contrast with 47% of patients in the waitlist group. Mixed factorial analyses of variance revealed that, compared with the waitlist group, patients treated with ABFT showed a significantly greater reduction in both depressive and anxiety symptoms and family conflict. Of the 15 treated cases assessed at the follow-up, 13 patients (87%) continued to not meet criteria for MDD 6 months after treatment ended. CONCLUSIONS: ABFT appears to be a promising treatment and worthy of further development.     

Adolescent depression: Controlled desipramine treatment and atypical features

The study was designed to test the efficacy of desipramine in adolescents with major depression (MDD). In addition, we assessed the presence of atypical features of MDD, consisting of mood reactivity and two of four associated features (rejection sensitivity, hyperphagia, hypersomnia, and leaden paralysis). Patients were randomized to desipramine (DMI) or placebo for 6 weeks, provided they failed to improve (e.g., meeting MDD criteria and a Hamilton Depression Scale score ≥18) after 2 weeks on single blind placebo. Of 94 adolescents (ages 13–18) who were diagnosed as having MDD, 64 entered the study and 62 received placebo for 2 weeks. Of these, 45 were randomized to DMI or placebo. Completer analyses did not reveal significant improvement for the active treatment compared to the placebo. A large proportion of adolescents responded to placebo (50%), suggesting the need for very large samples to detect differential treatment efficacy, should it exist. A relatively high rate of atypical depression was observed (47% in the 64 patients entered). In view of the demonstrated specificity of monoamine oxidase inhibitor efficacy in adults with atypical features of MDD, this clinical subtype may have relevance to future investigation of therapeutic interventions in adolescent MDD. Depression and Anxiety 7:15–31, 1998. © 1998 Wiley-Liss, Inc.     

Are there temperament differences between major depression and dysthymic disorder in adolescent clinical outpatients?

AimsThe aim of the study was to explore possible differences in temperament and character dimensions between 2 monodiagnostic adolescent groups of depression, namely, one with a present episode of major depression and subjects with the other being their dysthymic peers.SampleFrom a multisite Western Hungarian sample of consecutively referred 14- to 18-year-old new psychiatric adolescent outpatients, 2 groups were compared: group I, n = 56 (9 males, 47 females), with major depressive disorder (MDD) and group II, n = 27 (6 males, 21 females), with a diagnosis of dysthymic disorder (DD). All other comorbid diagnoses including bipolar and double depression (MDD + DD) cases were excluded. Present suicide events, if the attempter had an underlying diagnosis of depression, were not causes for exclusion. Assessment methods used were the adapted Hungarian versions of the Mini International Neuropsychiatric Interview and the Junior Temperament (Cloninger) Character Inventory.ResultsThe only difference between the major depressive and dysthymic adolescents was harm avoidance, adolescents with major depression having a higher level practice of harm avoidance, whereas the temperament type of MDD vs DD seems to differ only in the aspect of avoiding painful stress. Expectations regarding a worse degree of self-directedness and lower levels of persistence and cooperativeness in the MDD sample were not proved.ConclusionsNo essential temperament differences were found between the 2 adolescent depressive groups. Scarce differences between temperament qualities of MDD and DD may support Akiskal's continuum theory of depressive disorders. More research and the use of closer clinical personality typologies are warranted to explore possible personality trait differences (if they exist) between clinical diagnostic groups of adolescent patients.     

Pharmacological treatment of adolescent major depression

Antidepressant agents are widely prescribed for adolescents, although specific data regarding their efficacy in this age range are limited. The aims of the present article are to review research findings regarding the use of antidepressant drugs for adolescent depression and to discuss the main results in light of our clinical experience. Only 13 controlled trials on the use of antidepressant drugs for adolescent major depression are available in the literature. Six studies evaluated the efficacy of tricyclic antidepressants, yet they only included 196 adolescents altogether. Seven studies, including a total of 1,403 patients, evaluated the efficacy of three specific serotonin reuptake inhibitors: fluoxetine, paroxetine, and sertraline. Based on published data, serotonin reuptake inhibitors appear to be the first-line psychopharmacologic treatment for adolescent depression, as three compounds (fluoxetine, paroxetine, and sertraline) appeared to be effective in this indication. Conversely, all published studies failed to demonstrate that the tricyclic antidepressants were superior to placebo. Several questions remain open and are discussed: How should we use available scientific data in clinical practice? Are there nonspecific factors implicated in treatment response? Is there a serotonin hypothesis for juvenile depression? What are the priorities for future research?     

Differences in the clinical characteristics of adolescent depressive disorders

Our objective was to analyze differences in clinical characteristics and comorbidity between different types of adolescent depressive disorders. A sample of 218 consecutive adolescent (ages 13-19 years) psychiatric outpatients with depressive disorders was interviewed for DSM-IV Axis I and Axis II diagnoses. We obtained data by interviewing the adolescents themselves and collecting additional background information from the clinical records. Lifetime age of onset for depression, current episode duration, frequency of suicidal behavior, psychosocial impairment, and the number of current comorbid psychiatric disorders varied between adolescent depressive disorder categories. The type of co-occurring disorder was mainly consistent across depressive disorders. Minor depression and dysthymia (DY) presented as milder depressions, whereas bipolar depression (BPD) and double depression [DD; i.e., DY with superimposed major depressive disorder (MDD)] appeared as especially severe conditions. Only earlier lifetime onset distinguished recurrent MDD from first-episode MDD, and newly emergent MDD appeared to be as impairing as recurrent MDD. Adolescent depressive disorder categories differ in many clinically relevant aspects, with most differences reflecting a continuum of depression severity. Identification of bipolarity and the subgroup with DD seems especially warranted. First episode MDD should be considered as severe a disorder as recurring MDD.     

Depression, suicidal behavior and insight in adolescents with schizophrenia

OBJECTIVES: To investigate the interrelationships between depressive symptoms of adolescent schizophrenia, post-psychotic depression (PPD), negative signs, suicidal behavior and insights into the disease. METHODS: Three groups of 16 adolescent inpatients were assessed with regard to: Schizophrenia alone, schizophrenia with PPD and major depressive disorder (MDD). The following measures were used: DSM IV diagnostic criteria, the Calgary Depression Scale for Schizophrenia (CDSS), the PANSS (Positive and Negative Signs of Schizophrenia Scale), (BDI) Beck Depression Inventory, (CCL) Cognitive Check List, (HS) Hopelessness Scale, (SRS) Suicide Risk Scale, (CSPS) Child Suicide Potential Scale and the (SAUMD) Scale to Assess Unawareness of Mental Disorder. RESULTS: Compared with MDD adolescents, PPD adolescents showed few somatic and behavioral symptoms of depression but had equally severe cognitive and affective depressive symptomatology. Suicide risk scores and actual suicidal behavior was prominent in PPD adolescents. A positive and significant correlation was found between PPD symptoms, suicide risk and awareness of disease (insight). Negative symptoms of schizophrenia could be distinguished from PPD symptoms and there was a negative correlation between blunted affect and PPD scores. CONCLUSIONS: PPD can be diagnosed in adolescent schizophrenia. The symptom pattern is different from MDD, therefore, there may be cause to modify DSM IV provisional criteria for this condition. Adolescents with schizophrenia who have insight into their illness are at higher risk for suicidal behavior and the development of PPD.     

Polymorphisms of androgen receptor gene in childhood and adolescent males with first-onset major depressive disorder and association with related symptomatology

This study was designed to explore the association between CAG repeats in AR gene and major depressive disorder (MDD) in male children and adolescents. The results showed that there were differences between adolescent depressive patients and adolescent controls in CAG repeats' length and alleles' distributions, and the severity of depression and anxiety was negatively correlated with the length of CAG repeats in adolescent patients. This suggested that AR gene might be involved in the depressive upset in adolescents, and the age- and sex-related prevalent differences might also be associated to CAG repeats.     

Adjunctive quetiapine for treatment-resistant adolescent major depressive disorder: a case series

BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability and mortality in adolescents. Empirical evidence suggests that many adolescents with MDD do not respond or respond only partially to commonly used interventions (antidepressants, psychotherapy, or a combination of antidepressants and psychotherapy). There is preliminary data in adults that adjunctive second-generation antipsychotics may be useful in treatment-resistant depression. OBJECTIVE: The aim of this study was to obtain preliminary data regarding the safety, tolerability, and clinical usefulness of quetiapine as adjunctive therapy for adolescents (13-18 years of age) diagnosed with treatment-resistant MDD. Treatment-resistant MDD was defined as a failure to respond to an adequate dose for at least 8 weeks of a selective serotonin reuptake inhibitor (SSRI). METHODS: The medical charts of 10 adolescents (13-18 years of age) diagnosed with treatment- resistant MDD, who were treated with adjunctive quetiapine, were evaluated. Doses of preexisting antidepressants remained unchanged during the period of evaluation. Response to treatment was defined as a Clinical Global Impression-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved). RESULTS: Seven adolescents (70%) qualified as responders to treatment with adjunctive quetiapine. The median dose of quetiapine was 200 mg (mean +/- SD = 275 +/- 190.4 mg, range; 150-800 mg). Side effects included sedation (40%) and weight gain (mean +/- SD = 4.5 +/- 7.24 pounds). There was no serious adverse event. CONCLUSIONS: This case series suggests that there may be a role for adjunctive quetiapine in treatment-resistant adolescent depression. Clinical safety and efficacy trials of quetiapine in this population appear to be warranted.     

Developmentally informed pharmacotherapy for child and adolescent depressive disorders

This article reviews evidence-based pharmacotherapy for children and adolescents with depression. Several randomized controlled trials (RCTs) support the use of fluoxetine for the treatment of childhood and adolescent depression as well as escitalopram in the treatment of adolescent depression. To date, one RCT has demonstrated the effectiveness of sertraline or citalopram for the treatment of major depressive disorder in youth. Only a small number of RCTs for depression have included children, and none of these trials were adequately powered to detect differences in the efficacy of medication between children and adolescents.     

Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled,randomized clinical trial

BACKGROUND: This report presents results from the acute treatment phase of a clinical trial designed to confirm efficacy of a fixed dose of 20 mg of fluoxetine in children and adolescents with major depressive disorder (MDD). METHOD: After a 3-week screening period, 122 children and 97 adolescents with MDD ( ) were randomly assigned to placebo or fluoxetine. After a 1-week placebo lead-in, fluoxetine-treated patients received fluoxetine 10 mg/day for 1 week, then fluoxetine 20 mg/day for 8 weeks. RESULTS: Fluoxetine was associated with greater mean improvement in Children's Depression Rating Scale-Revised (CDRS-R) score than placebo after 1 week ( <.05) and throughout the study period. Significantly more fluoxetine-treated patients (41%) met the prospectively defined criteria for remission than did placebo-treated patients (20%) ( <.01). More fluoxetine- (65%) than placebo-treated (53%) patients met the prospectively defined response criterion of > or =30% decrease in CDRS-R score, but this difference was not significant ( =.093). Significantly more fluoxetine-than placebo-treated patients completed acute treatment ( =.001). There were no significant differences between treatment groups in discontinuations due to adverse events ( =.408). CONCLUSION: Fluoxetine 20 mg daily appears to be well tolerated and effective for acute treatment of MDD in child and adolescent outpatients. Fluoxetine is the only antidepressant that has demonstrated efficacy in two placebo-controlled, randomized clinical trials of pediatric depression.     

Cognitive-behavioral psychotherapy for anxiety and depressive disorders in children and adolescents: an evidence-based medicine review

OBJECTIVE: To review the literature on the cognitive-behavioral treatment of children and adolescents with anxiety and depressive disorders within the conceptual framework of evidence-based medicine. METHOD: The psychiatric and psychological literature was systematically searched for controlled trials applying cognitive-behavioral treatment to pediatric anxiety and depressive disorders. RESULTS: For both anxiety and depression, substantial evidence supports the efficacy of problem-specific cognitive-behavioral interventions. Comparisons with wait-list, inactive control, and active control conditions suggest medium to large effects for symptom reduction in primary outcome domains. CONCLUSIONS: From an evidence-based perspective, cognitive-behavioral therapy is currently the treatment of choice for anxiety and depressive disorders in children and adolescents. Future research in this area will need to focus on comparing cognitive-behavioral psychotherapy with other treatments, component analyses, and the application of exportable protocol-driven treatments to divergent settings and patient populations.     

Predicting Mental Health Treatment Access Among Adolescents With Elevated Depressive Symptoms: Machine Learning Approaches

A large proportion of adolescents experiencing depression never access treatment. To increase access to effective mental health care, it is critical to understand factors associated with increased versus decreased odds of adolescent treatment access. This study used individual depression symptoms and sociodemographic variables to predict whether and where adolescents with depression accessed mental health treatments. We performed a pre-registered, secondary analysis of data from the 2017 National Survey of Drug Use and Health (NSDUH), a nationally representative sample of non-institutionalized civilians in the United States. Using four cross-validated random forest models, we predicted whether adolescents with elevated past-year depressive symptoms (N?=?1,671; ages 12–17 years) accessed specific mental health treatments in the previous 12 months (“yes/no” for inpatient, outpatient, school, any). 53.38% of adolescents with elevated depressive symptoms accessed treatment of any kind. Even with depressive symptoms and sociodemographic factors included as predictors, pre-registered random forests explained?<?0.00% of pseudo out-of-sample deviance in adolescent access to inpatient, outpatient, school, or overall treatments. Exploratory elastic net models explained 0.80–2.50% of pseudo out-of-sample deviance in adolescent treatment access across all four treatment types. Neither individual depressive symptoms nor any socioeconomic variables meaningfully predicted specific or overall mental health treatment access in adolescents with elevated past-year symptoms. This study highlights substantial limitations in our capacity to predict whether and where adolescents access mental health treatment and underscores the broader need for more accessible, scalable adolescent depression treatments.