The Treatment for Adolescents with Depression Study (TADS): methods and message at 12 weeks

Funded by the National Institute of Mental Health, the Treatment for Adolescents With Depression Study (TADS) is intended to evaluate the short-term (12 weeks) and longer-term (36 weeks) effectiveness of four treatments for adolescents with DSM-IV major depressive disorder: clinical management with fluoxetine (FLX), cognitive-behavioral therapy (CBT), FLX and CBT combined (COMB), and clinical management with placebo (PBO). We previously reported that COMB and FLX were more effective in reducing depression than CBT or PBO after 12 weeks of acute treatment. In this special section of the Journal, separate articles extend these findings to the impact of TADS treatments on remission, speed of response, function and quality of life, predictors of outcome, and safety during the first 12 weeks of treatment. To set the stage for the special section, we briefly review the rationale, design, and methods of the TADS; describe the TADS sample to which the TADS findings generalize; using all of the currently available data, summarize the intent-to-treat outcomes across multiple endpoints at 12 weeks; and consider the public health value of the TADS findings in the context of design decisions and methodological limitations of the TADS, including some that may have advantaged the combined treatment condition. Reflecting the ordering of effect sizes at week 12--COMB (0.98) > FLX (0.68) > CBT (-0.03)--combined treatment proved superior to PBO on 15 of 16 endpoints, to CBT on 14 of 16 endpoints, and to FLX on 8 of 16 endpoints, whereas FLX was superior to CBT on 8 of 14 and to PBO on 7 of 16 measures. CBT did not differ from PBO on any measure. Despite the fact that suicidality improved markedly across all of the treatment conditions, suicidal events were twice as common in patients treated with FLX alone than with COMB or CBT alone, perhaps indicating that CBT protects against suicidal events. Thus, combined treatment appears to accelerate recovery relative to CBT and, for some outcomes, FLX alone, while minimizing the risk of suicidality relative to FLX alone. Taking benefit and risk into account, we conclude that the combination of FLX and CBT appears superior to either monotherapy as a treatment for moderate to severe major depressive disorder in adolescents.     

Group behavioral therapy for adolescents with tic-related and non-tic-related obsessive-compulsive disorder

Prior research supports the distinction between tic-related and non-tic-related obsessive-compulsive disorder (OCD) based on phenomenologic, etiologic, and neurobehavioral data. The present study examines whether response to psychosocial treatment differs in adolescents, depending on the presence of comorbid tics. Nineteen adolescents, 12-17 years of age, participated in 7-week, uncontrolled trial of group cognitive-behavioral treatment (CBT) for OCD. Eight of the patients had tic-related and eleven had non-tic-related OCD. The group CBT program included psycho-education, exposure and response prevention, cognitive strategies, and family involvement. Significant improvement was observed for all subjects on the Yale-Brown Obsessive Compulsive Scale ratings of obsessions, compulsions, and total OCD symptoms. Outcomes were similar for subjects with tic-related and non-tic-related OCD. These preliminary results suggest that the presence of comorbid tic disorders may not attenuate response to behavioral group treatment among adolescents.     

Acute time to response in the Treatment for Adolescents with Depression Study (TADS)

OBJECTIVE: To examine the time to response for both pharmacotherapy and psychotherapy in the Treatment for Adolescents with Depression Study (TADS). METHOD: Adolescents (N = 439, ages 12 to 17 years) with major depressive disorder were randomized to fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or pill placebo (PBO). Defining response as very much improved or much improved on the Clinical Global Impression-Improvement Scale (CGI-I), survival analyses using Cox proportional hazards models, and Kaplan-Meier curves were conducted to evaluate time to first response and time to stable response for subjects receiving pharmacotherapy (COMB, FLX, PBO) as well as for subjects receiving CBT (COMB, CBT). Direct comparisons between pharmacotherapy and CBT were not made because of differences in visit schedules. RESULTS: Based on pharmacotherapist CGI-I scores, COMB and FLX showed faster onset of benefit than PBO on time to response and time to stable response (p < .001), and COMB was faster than FLX on time to stable response (p = .034). The probability of sustained early response was approximately threefold greater for COMB than PBO, twofold greater for FLX than PBO, and 1.5-fold greater for COMB than FLX. On the psychotherapist CGI-I scores, both first response and stable response occurred faster in COMB than CBT (p < .001), with a probability of sustained early response approximately threefold greater for COMB than CBT. CONCLUSIONS: In the acute treatment of depressed adolescents, FLX and COMB accelerate response relative to PBO, and COMB accelerates response relative to CBT alone.     

Remission and residual symptoms after short-term treatment in the Treatment of Adolescents with Depression Study (TADS)

OBJECTIVE: To ascertain remission rates in depressed youth participating in the Treatment for Adolescents With Depression Study (TADS), a multisite clinical trial that randomized 439 adolescents with major depressive disorder (MDD) to a 12-week treatment of fluoxetine (FLX), cognitive-behavioral therapy (CBT), their combination (COMB), or clinical management with pill placebo (PBO). METHOD: Using an end-of-treatment Children's Depression Rating Scale-Revised (CDRS-R) total score of 28 or below as the criterion for remission, rates of remission were examined with logistic regression, controlling for site. Loss of MDD diagnosis and residual symptoms in responders (defined as Clinical Global Impressions-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved) were also examined across treatment groups. RESULTS: After 12 weeks of treatment, 102 (23%) of 439 youths had reached remission. The remission rate was significantly higher in the COMB group (37%) relative to the other treatment groups (FLX, 23%; CBT, 16%; PBO, 17%), with odds ratios of 2.1 for COMB versus FLX, 3.3 for COMB versus CBT, and 3.0 for COMB versus PBO. In addition, 71% of subjects across treatment groups no longer met criteria for MDD at the end of acute treatment. Fifty percent of the youths who responded by CGI-I criteria continued to have residual symptoms, such as sleep or mood disturbances, fatigue, and poor concentration. CONCLUSIONS: The combination of FLX and CBT was superior to both monotherapy and PBO in terms of remission rates, but overall rates of remission remain low and residual symptoms are common at the end of 12 weeks of treatment.     

认知行为疗法治疗儿童青少年强迫症的脑影像学研究进展

50%的成人强迫症患者在童年或青少年期已出现强迫症的早期症状,及早干预可有效降低成人强迫症的患病率。认知行为疗法（cognitive behavioral therapy, CBT）是有效治疗儿童青少年强迫症的心理疗法之一,但目前其治疗机制尚未明确。近年来,脑影像学发展迅速,为探究CBT治疗的脑机制提供了重要的神经影像...     

Treatment outcome for adolescent obsessive-compulsive disorder in a specialized hospital setting

Although few data are available concerning adolescents with obsessive-compulsive disorder (OCD), the existing literature suggests that cognitive-behavioral therapy (CBT) is the first-line treatment of choice for adolescents with mild to moderate OCD. A combination of CBT and serotonin reuptake inhibitors (SRIs) is recommended for more severe forms of OCD, based on the Expert Consensus Guidelines for the Treatment of Obsessive-Compulsive Disorder and the Pediatric OCD Treatment Study (POTS). Despite the effectiveness of CBT, a recent meta-analysis found that 27% of adolescent outpatients fail to show clinically significant improvement following CBT and many also fail to show improvement with pharmacotherapy. One alternative for those who do not improve with outpatient treatment is an intensive inpatient program. Within the last 10 years, two specialty hospitals have created programs that provide intensive CBT milieu treatment with multidisciplinary support (e.g., nursing, psychopharmacology) to treat adolescents with OCD. This naturalistic study describes treatment outcomes in 23 patients who received treatment in one of these programs between 2005 and 2006. Results suggest significant improvements on the majority of outcome measures, with 70% of the patients judged to meet criteria for clinically significant change. Thus, inpatient treatment appears potentially efficacious, although future controlled trials with larger samples are needed.     

Obsessive-compulsive disorder in youth with and without a chronic tic disorder

The goal of this study was to discriminate subtypes of pediatric obsessive-compulsive disorder (OCD) among youth with and without a comorbid tic disorder. Seventy-four youth (M(age)=9.7+/-2.3 years) with a principal diagnosis of OCD, with (n=46) or without (n=28) a comorbid tic disorder, were assessed with a semi-structured diagnostic interview and the Children's Yale Brown Obsessive-Compulsive Scale (CY-BOCS). The CY-BOCS Symptom Checklist was used to categorize obsessions and compulsions. Group differences were analyzed by t tests, chi(2), and discriminant function analyses. Results suggested that subjects without tics had significantly more contamination obsessions, sexual obsessions, and counting compulsions than youth with comorbid tics. Generally speaking, however, youth with and without tics had similar symptom presentations. These data suggest that pediatric OCD patients with and without comorbid tics may have some aspects of symptom presentation that differ, but generally have more OCD symptoms in common than different. Implications of these findings on clinical presentation and treatment efficacy are highlighted.     

Treatment for Adolescents with Depression Study (TADS): safety results

OBJECTIVE: To compare the rates of physical, psychiatric, and suicide-related events in adolescents with MDD treated with fluoxetine alone (FLX), cognitive-behavioral therapy (CBT), combination treatment (COMB), or placebo (PBO). METHOD: Safety assessments included adverse events (AEs) collected by spontaneous report, as well as systematic measures for specific physical and psychiatric symptoms. Suicidal ideation and suicidal behavior were systematically assessed by self- and clinician reports. Suicidal events were also reanalyzed by the Columbia Group and expert raters using the Columbia-Classification Algorithm for Suicidal Assessment used in the U.S. Food and Drug Administration reclassification effort. RESULTS: Depressed adolescents reported high rates of physical symptoms at baseline, which improved as depression improved. Sedation, insomnia, vomiting, and upper abdominal pain occurred in at least 2% of those treated with FLX and/or COMB and at twice the rate of placebo. The rate of psychiatric AEs was 11% in FLX, 5.6% in COMB, 4.5% in PBO, and 0.9% in CBT. Suicidal ideation improved overall, with greatest improvement in COMB. Twenty-four suicide-related events occurred during the 12-week period: 5 patients (4.7%) in COMB, 10 (9.2%) in FLX, 5 (4.5%) in CBT, and 3 (2.7%) in placebo. Statistically, only FLX had more suicide-related events than PBO (p =.0402, odds ratio (OR) = 3.7, 95% CI 1.00-63.7). Only five actual attempts occurred (2 COMB, 2 FLX, 1 CBT, 0 PBO). There were no suicide completions. CONCLUSIONS: Different methods for eliciting AEs produce different results. In general, as depression improves, physical complaints and suicidal ideation decrease in proportion to treatment benefit. In this study, psychiatric AEs and suicide-related events are more common in FLX-treated patients. COMB treatment may offer a more favorable safety profile than medication alone in adolescent depression.     

Cognitive-behavior therapy of obsessive-compulsive disorder in private practice: an effectiveness study

A controversy exists over whether or not the results of randomized controlled trials (RCTs) are generalizable to routine clinical practice. The present study examines the effectiveness of cognitive-behavior therapy (CBT) for obsessive-compulsive disorder (OCD) in a private practice setting. Twenty-six consecutive clients referred to a private anxiety disorders specialty clinic began treatment for OCD. Of the 19 (73%) clients who completed treatment, 84% were treatment responders. Clients, treatment, and outcome of the present study are compared with those of representative RCTs, and it is concluded that there are more similarities than differences. It is concluded that CBT can be effectively delivered in routine clinical practice.     

Cognitive behavioral therapy for pediatric obsessive-compulsive disorder: Development of expert-level competence and implications for dissemination

Pediatric obsessive-compulsive disorder (OCD) is associated with substantial morbidity, comorbidity, family difficulties, and functional impairment. Fortunately, OCD in youth has also been found responsive to cognitive behavioral therapy (CBT) both alone and in combination with medication. This paper highlights key areas a treatment provider must be highly knowledgeable in to be considered an expert in cognitive behavioral therapy (CBT) for pediatric obsessive-compulsive disorder (OCD). We describe the areas of knowledge that must be mastered to gain expertise, as well as the more difficult to quantify personal qualities that may allow a clinician to convey this knowledge in an expert manner. We provide detailed discussions of CBT theory, assessment strategies, implications of the treatment outcome literature for clinical decision-making, and how best to navigate CBT. We also discuss what the expert needs to accomplish by engaging youth and families throughout the evaluation and treatment process.     

Aripiprazole augmentation of incomplete treatment response in an adolescent male with obsessive-compulsive disorder

We report the case of adolescent male with obsessive-compulsive disorder (OCD) who had an incomplete response to combined cognitive-behavioral therapy (CBT) and sertraline before successful augmentation of CBT with aripiprazole. Standardized assessments indicated significant reductions in OCD symptomatology associated with both initial treatment and aripiprazole augmentation. This case suggests that aripiprazole may have utility as an augmenting agent of CBT in adolescents with OCD and underscores the need for conducting controlled studies to test this hypothesis.     

Comorbidity of obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in referred children and adolescents

OBJECTIVE: The aim of this study was to explore whether comorbid attention-deficit/hyperactivity disorder (ADHD) affects the clinical expression and outcome of obsessive-compulsive disorder (OCD) in a clinical sample. METHOD: A consecutive series of 94 children and adolescents (mean age, 13.6 +/- 2.8 years) with current diagnosis of OCD were included in the study. Twenty-four (25.5%) patients were diagnosed as having a comorbid ADHD. Subjects with OCD plus ADHD were compared with subjects with OCD but without ADHD. RESULTS: Comorbid ADHD with OCD was significantly associated with a higher rate of males, an earlier onset of OCD, a greater psychosocial impairment, and a heavier comorbidity, namely, with bipolar disorder, tic disorder, and oppositional defiant disorder/conduct disorder. Phenomenology of obsessions and compulsions and outcome were not affected by ADHD comorbidity. CONCLUSIONS: A screening for ADHD should be performed in patients with OCD, as these patients and their parents are frequently not aware that the impairment may be partly due to a comorbid ADHD.     

Thérapie comportementale et cognitive du trouble obsessionnel et compulsif et des troubles de la personnalité comorbides : thérapie de groupe

Obsessive-compulsive disorder (OCD) is a chronic, recurrent, and often disabling disorder. Comorbid emotional and personality disorder are common and can serve to complicate both course of illness and treatment outcome. Controlled trials with adults have shown cognitive-behavior therapy (CBT) that includes exposure and response prevention (ERP) to be highly effective for treating the disorder. It means exposing the patient to the very thing that causes fear and anxiety, and using all his strength to simply accept the experience instead of relying on compulsions to counteract it. The basic concept of CBT is: by changing the behavior, the patient eventually changes how he thinks and feels. CBT usually works fairly quickly, and it relies mostly on action, not insight. In this article we describe a cognitive-behavioral group treatment for both OCD symptoms and comorbid personality disorder. By an evaluable patient analysis; statistically and clinically significant pretreatment to posttreatment change occurred in OCD diagnostic status and severity. Some personality traits also changed. The results of this study, the first to evaluate this dimension of the personality disorders comorbidities in the OCD and their evolution with a behavioural and cognitive psychotherapy, are very encouraging. Indeed, evolution of the fields and facets of the personality changed positively.     

A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder

BACKGROUND: To date, only 1 controlled study has found a drug (haloperidol) to be efficacious in augmenting response in patients with obsessive-compulsive disorder (OCD) refractory to serotonin reuptake inhibitor (SRI) monotherapy; patients with comorbid chronic tic disorders showed a preferential response. This report describes the first controlled study of risperidone addition in patients with OCD refractory to treatment with SRI alone. METHODS: Seventy adult patients with a primary DSM-IV diagnosis of OCD received 12 weeks of treatment with an SRI. Thirty-six patients were refractory to the SRI and were randomized in a double-blind manner to 6 weeks of risperidone (n = 20) or placebo (n = 16) addition. Behavioral ratings, including the Yale-Brown Obsessive Compulsive Scale, were obtained at baseline and throughout the trial. Placebo-treated patients subsequently received an identical open-label trial of risperidone addition. RESULTS: For study completers, 9 (50%) of 18 risperidone-treated patients were responders (mean daily dose, 2.2 +/-0.7 mg/d) compared with 0 of 15 in the placebo addition group (P<. 005). Seven (50%) of 14 patients who received open-label risperidone addition responded. Risperidone addition was superior to placebo in reducing OCD (P<.001), depressive (P<.001), and anxiety (P =.003) symptoms. There was no difference in response between OCD patients with and without comorbid diagnoses of chronic tic disorder or schizotypal personalty disorder. Other than mild, transient sedation, risperidone was well tolerated. CONCLUSION: These results suggest that OCD patients with and without comorbid chronic tic disorders or schizotypal personality disorder may respond to the addition of low-dose risperidone to ongoing SRI therapy.     

Cognitive-behavioral therapy for PANDAS-related obsessive-compulsive disorder: findings from a preliminary waitlist controlled open trial

OBJECTIVE: To provide preliminary estimates of the effectiveness of cognitive-behavioral therapy (CBT) in treating pediatric obsessive-compulsive disorder (OCD) of the pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS) subtype. METHOD: Seven children with OCD of the PANDAS subtype (range 9-13 years) were treated in a 3-week intensive CBT program conducted at a university clinic. Six of seven children were taking selective serotonin reuptake inhibitor medication(s) upon presentation. Assessments were conducted at four time points: baseline, pretreatment approximately 4 weeks later, posttreatment, and 3-month follow-up. Raters were blind to the nature of the study treatment. RESULTS: Six of seven participants were classified as treatment responders (much or very much improved) at posttreatment, and three of six remained responders at follow-up. Clinician severity ratings, as measured by the Children's Yale-Brown Obsessive-Compulsive Scale and Anxiety Disorder Interview Schedule for DSM-IV Child Interview Schedule-Parent version, decreased significantly following intervention, with effect sizes of 3.38 and 2.29, respectively. Self-reported general anxiety and depression symptoms were not significantly reduced. CONCLUSIONS: This study provides preliminary support for CBT in treating the PANDAS subtype of pediatric OCD. This approach is also considered a safe and minimally invasive treatment approach.     

Attention-deficit/hyperactivity disorder in children and adolescents with obsessive-compulsive disorder: fact or artifact?

OBJECTIVE: To clarify whether the symptoms of inattention and distractibility commonly seen in children and adolescents with obsessive-compulsive disorder (OCD) represent true comorbidity with attention-deficit/hyperactivity disorder (ADHD) or a manifestation of obsessional anxiety. METHOD: Phenotypic features and functional correlates of ADHD-like symptoms were examined in youths with and without OCD from a large sample of pediatric psychiatry patients consecutively referred since 1997. RESULTS: The number, frequency, and types of core ADHD symptoms as well as ADHD-associated functional indices were identical in all youths with DSM-IV-diagnosed ADHD irrespective of the presence or absence of comorbid OCD. CONCLUSION: These findings suggest that when ADHD-like symptoms are seen in youths with OCD, they reflect a true comorbid state of OCD plus ADHD and that the ADHD syndrome may be independent of OCD in comorbid youths.     

An Evaluation of a New Autism-Adapted Cognitive Behaviour Therapy Manual for Adolescents with Obsessive–Compulsive Disorder

Obsessive–compulsive disorder (OCD) and autism spectrum disorder (ASD) frequently co-occur. Standard cognitive behaviour therapy (CBT) for OCD outcomes are poorer in young people with ASD, compared to those without. The aim of this naturalistic study was to evaluate the effectiveness of a novel adolescent autism-adapted CBT manual for OCD in a specialist clinical setting. Additionally, we examined whether treatment gains were maintained at 3-month follow-up. Thirty-four adolescents underwent CBT; at the end of treatment, 51.51% were treatment responders and 21.21% were in remission. At 3-month follow-up, 52.94% were responders and 35.29% remitters. Significant improvements were also observed on a range of secondary measures, including family accommodation and global functioning. This study indicates this adapted package of CBT is associated with significant improvements in OCD outcomes, with superior outcomes to those reported in previous studies. Further investigation of the generalizability of these results, as well as dissemination to different settings, is warranted.

     

An Initial Case Series of Intensive Cognitive–Behavioral Therapy for Obsessive–Compulsive Disorder in Adolescents with Autism Spectrum Disorder

Obsessive–compulsive disorder (OCD) is prevalent among youth with autism spectrum disorder (ASD). Cognitive–behavioral therapy (CBT) with ASD-specific modifications has support for treating OCD in this population; however, use of intensive CBT in youth with ASD and severe OCD has not been tested. The current study examined the preliminary effectiveness of an individualized intensive CBT protocol for OCD in adolescents with ASD. Nine adolescents (aged 11–17 years) completed a regimen of intensive CBT (range 24–80 daily sessions) incorporating exposure with response prevention (ERP). Treatment materials, language and techniques were modified in accordance with evidence-based findings for this population. Seven of nine participants (78%) were treatment responders, and large treatment effects (d?=?1.35–2.58) were obtained on primary outcomes (e.g., obsessive–compulsive symptom severity). Preliminary findings suggest that an intensive CBT approach for OCD is effective among adolescents with ASD.     

Cognitive therapy and exposure in vivo alone and in combination with fluvoxamine in obsessive-compulsive disorder: a 5-year follow-up

BACKGROUND: Information regarding the long-term effectiveness of the combination of pharmacotherapy and cognitive-behavioral therapy (CBT) in the treatment of obsessive-compulsive disorder (OCD) is limited. Our study is the first to examine the long-term effectiveness of cognitive therapy (CT) and to compare long-term effectiveness of CT alone, exposure in vivo with response prevention (ERP) alone, and CBT (either CT or ERP) in combination with fluvoxamine in the treatment of OCD. METHOD: Of 122 outpatients with primary DSM-III-R-defined OCD originally enrolled in 2 randomized controlled trials, 102 patients (45 male/57 female; mean +/- SD age = 36.2 +/- 10.7 years; range, 19-64 years) were available to be assessed for the presence and severity of OCD and comorbid psychopathology at follow-up. Follow-up data were collected from November 1996 to June 1999. RESULTS: After 5 years, 54% of the participants no longer met the DSM-III-R criteria for OCD. Long-term outcome did not differ between the 3 treatment groups. At follow-up, treatment dropouts appeared to have more severe OCD complaints compared with treatment completers. Compared with patients receiving CT alone, significantly (p < .005) more patients receiving CBT with fluvoxamine used antidepressants 5 years later. CONCLUSIONS: This study demonstrates that at 5-year follow-up (1) prevalence of OCD had declined in all 3 treatment conditions, (2) the clinical benefits of all 3 treatment conditions were maintained, (3) OCD complaints were more severe for treatment dropouts than for treatment completers, and (4) about half of the patients initially treated with fluvoxamine continued antidepressant use.     

Family-based cognitive-behavioral therapy for pediatric obsessive-compulsive disorder: comparison of intensive and weekly approaches

OBJECTIVE: To examine the relative efficacy of intensive versus weekly cognitive-behavioral therapy (CBT) for children and adolescents with obsessive-compulsive disorder (OCD). METHOD: Forty children and adolescents with OCD (range 7-17 years) were randomized to receive 14 sessions of weekly or intensive (daily psychotherapy sessions) family-based CBT. Assessments were conducted at three time points: pretreatment, posttreatment, and 3-month follow-up. Raters were initially blind to randomization. Primary outcomes included scores on the Children's Yale-Brown Obsessive-Compulsive Scale, remission status, and ratings on the Clinical Global Impression-Severity and Clinical Global Improvement scales. Secondary outcomes included the Child Obsessive Compulsive Impact Scale-Parent Rated, Children's Depression Inventory, Multidimensional Anxiety Scale for Children, and Family Accommodation Scale. Adjunctive pharmacotherapy was not an exclusion criterion. RESULTS: Intensive CBT was as effective as weekly treatment with some advantages present immediately after treatment. No group differences were found at follow-up, with gains being largely maintained over time. Although no group x time interaction was found for the Children's Yale-Brown Obsessive-Compulsive Scale (F(1,38) = 2.2, p = .15), the intensive group was rated on the Clinical Global Impression-Severity as less ill relative to the weekly group (F(1,38) = 9.4, p < .005). At posttreatment, 75% (15/20) of youths in the intensive group and 50% (10/20) in the weekly group met remission status criteria. Ninety percent (18/20) of youths in the intensive group and 65% (13/20) in the weekly group were considered treatment responders on the Clinical Global Improvement (chi1(2) = 3.6, p = .06). CONCLUSIONS: Both intensive and weekly CBT are efficacious treatments for pediatric OCD. Intensive treatment may have slight immediate advantages over weekly CBT, although both modalities have similar outcomes at 3-month follow-up.