Impact of childhood trauma on treatment outcome in the Treatment for Adolescents with Depression Study (TADS).

OBJECTIVE: 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). METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

The role of readiness to change in response to treatment of adolescent depression.

The effect of readiness to change on treatment outcome was examined among 332 adolescents (46% male, 74% Caucasian), ages 12 through 17 years (M = 14.6, SD = 1.5), with major depressive disorder who were participating in the Treatment for Adolescents With Depression Study (TADS). TADS is a randomized clinical trial comparing the effectiveness of fluoxetine (an antidepressant medication), cognitive-behavioral therapy, their combination, and a pill placebo. An abbreviated Stages of Change Questionnaire was used to obtain 4 readiness to change scores: precontemplation, contemplation, action, and maintenance. The association between each readiness score and depression severity across 12 weeks of acute treatment for depression, as measured by the Children's Depression Rating Scale--Revised, was examined. Although treatment response was not moderated by any of the readiness scores, baseline action scores predicted outcome: Higher action scores were associated with better outcome regardless of treatment modality. Furthermore, treatment effects were mediated by change in action scores during the first 6 weeks of treatment, with increases in action scores related to greater improvement in depression. Assessing readiness to change may have implications for tailoring treatments for depressed adolescents.

A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder.

We examined the antidepressant efficacy and dose-response pattern of the n-3 docosahexaenoic acid (DHA). Thirty-five depressed adult outpatients (46% women; mean age 42+/-14 years) with a 17-item Hamilton-Depression Scale (HAM-D-17) score of >or=18 were randomized into one of three double-blind dosing arms for 12 weeks. Group A (n=14): 1 g/day of oral DHA; Group B (n=11): 2 g/day; and Group C (n=10): 4 g/day. We measured HAM-D-17 scores, plasma DHA, eicosapentaenoic acid (EPA), and n-6/n-3 ratio. Completer response rates (>or=50% decrease in HAM-D-17 score) were 83% for Group A, 40% for Group B, and 0% for Group C; Groups A and B had significant decreases in HAM-D-17 scores (p<0.05). For completers and intent-to-treat subjects, plasma DHA increased significantly (p<0.05), EPA had little change (p>0.05), and n-6/n-3 decreased significantly (p<0.05). DHA may be effective for depression at lower doses.

Depressed adolescents and comorbid psychiatric disorders: are there differences in the presentation of depression?

Patterns and correlates of comorbidity, as well as differences in manifest depressive profiles were investigated in a sample of depressed adolescents. A sub-sample of the youth were characterized as belonging to either a Pure depression group, an Internalizing group (depression and co-occurring internalizing disorders), or an Externalizing group (depression and co-occurring externalizing disorders). Item response theory (IRT) and differential item functioning (DIF) were used to assess whether the depressed adolescents from the different comorbidity groups presented with different depressive symptoms. Results indicated that the comorbidity groups were meaningfully distinct in terms of psychosocial correlates as well as showed differences in depressive symptom profiles as informed by DIF analyses. In particular, the comorbidity groups differed in terms of presentation of psychomotor changes and cognitive impairments. Implications for assessment are discussed.

Cultural considerations in adolescent suicide prevention and psychosocial treatment.

Ethnic groups differ in rates of suicidal behaviors among youths, the context within which suicidal behavior occurs (e.g., different precipitants, vulnerability and protective factors, and reactions to suicidal behaviors), and patterns of help-seeking. In this article, the authors discuss the cultural context of suicidal behavior among African American, American Indian and Alaska Native, Asian American and Pacific Islander, and Latino adolescents, and the implications of these contexts for suicide prevention and treatment. Several cross-cutting issues are discussed, including acculturative stress and protective factors within cultures; the roles of religion and spirituality and the family in culturally sensitive interventions; different manifestations and interpretations of distress in different cultures; and the impact of stigma and cultural distrust on help-seeking. The needs for culturally sensitive and community- based interventions are discussed, along with future opportunities for research in intervention development and evaluation.

Outcomes of recognizing depressed Chinese American patients in primary care.

PURPOSE: This study aims to examine the effect of identifying Chinese American patients as having major depressive disorder (MDD) to their primary care physicians (PCPs) on the latter's attention given to the treatment of depression. METHODOLOGY: Forty Chinese American patients from a primary care clinic were identified as having major depressive disorder (MDD), and their primary care physicians (PCPs) were notified of the diagnosis by letter. Three months later, medical records of subjects in the study were reviewed to see if their PCPs had intervened through referral and/or initiated treatment of depression. RESULTS: PCPs documented intervention in 19 patients (47%) regarding their depression. Two of these patients (11%) were started on an antidepressant. Four (21%) accepted and 13 (68%) declined referral to mental health services. No intervention was recorded for 21 (53%) patients. CONCLUSION: We conclude that recognition alone of MDD among Chinese Americans in the community primary care setting does not lead to adequate initiation of treatment for depression by PCPs.

Ziprasidone augmentation of selective serotonin reuptake inhibitors (SSRIs) for SSRI-resistant major depressive disorder.

BACKGROUND: Due to their favorable side-effect profile, atypical antipsychotic agents offer important therapeutic advantages in mood disorders. Ziprasidone, an atypical antipsychotic agent with strong 5-HT(1A) agonist activity, may be particularly useful when used in conjunction with standard antidepressants in treatment-resistant depression. The purpose of this study is to test this hypothesis in depressed outpatients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor (SSRI). METHOD: Twenty patients with major depressive disorder (MDD) who had failed to experience a clinical response to an adequate trial of an SSRI were treated with open-label ziprasidone in addition to their SSRI for 6 weeks between February 2002 and December 2002. MDD was diagnosed with the Structured Clinical Interview for DSM-IV Axis I disorders. Clinical response was defined as a 50% or greater decrease in depressive symptoms during the course of the trial (baseline to endpoint), as measured by the HAM-D-17 total score. RESULTS: Thirteen of 20 patients (65.0%) completed the trial. Using a completer analysis, 8 patients (61.5%) were classified as responders. An intent-to-treat (ITT) analysis resulted in 10 responders (50.0%). The overall proportion of remitters was 5 of 13 (38.5%) using a completer analysis and 5 of 20 (25.0%) using the ITT analysis. Ziprasidone administration appeared to be safe, with no clinically significant QTc prolongation or severe adverse events observed in any of the study participants. CONCLUSION: These results suggest a possible augmentation role for ziprasidone when used in conjunction with SSRIs in SSRI-resistant MDD.

Psychiatric comorbidity as a predictor of clinical response to nortriptyline in treatment-resistant major depressive disorder.

BACKGROUND: A number of studies of major depressive disorder suggest that psychiatric co-morbidity may contribute to treatment resistance. The purpose of this study was to test whether the presence of comorbid Axis I and Axis II disorders predicts clinical response to an open trial of nor-triptyline among patients with treatment-resistant depression. METHOD: Ninety-two outpatients with treatment-resistant DSM-III-R major depressive disorder were enrolled in a 6-week open trial of nor-triptyline (Nov. 1992-Jan. 1999). The presence of comorbid Axis I and Axis II disorders was established at baseline with the use of the Structured Clinical Interview for DSM-III-R. Chi-square analyses were used to test Axis I or Axis II co-morbid conditions as a predictor of clinical response to nortriptyline. RESULTS: Thirty-nine patients (42.4%) responded to nortriptyline. The presence of avoidant personality disorder (p <.01) predicted poorer response to nortriptyline. The response rate was 16.7% for patients with and 48.6% for patients without comorbid avoidant personality disorder. No other comorbid diagnoses were found to predict clinical response in a statistically significant manner. CONCLUSION: The presence of avoidant personality disorder conferred a poorer prognosis in treatment-resistant depression patients treated with nortriptyline.