Out of the Black Box: Treatment of Resistant Depression in Adolescents and the Antidepressant Controversy

Abstract

Objective: The purpose of this article is to describe the effects of the pediatric antidepressant controversy on the Treatment of Serotonin-Selective Reuptake Inhibitor (SSRI) Resistant Depression in Adolescents (TORDIA) trial. Method: Adolescents, ages 12-18 years, with SSRI resistant depression were randomized to one of four treatments for a 12 week trial: Switch to different SSRI, switch to an alternate antidepressant (venlafaxine), switch to an alternate SSRI plus cognitive behavior therapy (CBT), or switch to venlafaxine plus CBT. Results: The health advisories and ''black box'' warnings regarding suicidality and antidepressants in adolescents occurred during the course of the TORDIA trial. Revisions to the protocol, multiple-consent form changes, and re-consenting of patients were necessary. Recruitment of participants was adversely affected. Conclusion: Despite a cascade of unforeseen events that delayed the completion of the study, the TORDIA trial resulted in clinically important information about treatment-resistant depression in adolescents.

Measuring Cognitive Function in Mdd: Emerging Assessment Tools

“…[14] Strategic planning and organization were moderately impaired ( d = 0.44). Although only three of the 15 studies evaluated the effect of antidepressant medication treatment on cognition, results suggest that executive function improved with antidepressant treatment.…”

“…A recent meta-analysis, including patients with more chronic MDD, suggests that patients demonstrate significant impairment in response inhibition, cognitive flexibility, and semantic verbal fluency, with large effect sizes (Cohen's d = 1.18, 1.11, and 0.92, respectively). [14] Strategic planning and organization were moderately impaired (d = 0.44). Although only three of the 15 studies evaluated the effect of antidepressant medication treatment on cognition, results suggest that executive function improved with antidepressant treatment.…”

Analysis of Pediatric Clinical Drug Trials for Neuropsychiatric Conditions

“…[16][17][18] [19][20][21] The lack of clinical evidence to support the use of these agents in children has resulted in a number of controversies, including concerns over increased suicidality among adolescents treated with selective serotonin reuptake inhibitors and of antipsychotic side effects in young children. [22][23][24][25] We define the current state of pediatric research activity for neuropsychiatric disease, including the underrepresentation of certain drug classes and conditions. Specifically, we determine the proportion of clinical drug trials for neuropsychiatric conditions seeking to expand the evidence base for children and compare pediatric and adult research on these conditions.…”

Analysis of Pediatric Clinical Drug Trials for Neuropsychiatric Conditions

“…[19][20][21] The lack of clinical evidence to support the use of these agents in children has resulted in a number of controversies, including concerns over increased suicidality among adolescents treated with selective serotonin reuptake inhibitors and of antipsychotic side effects in young children. [22][23][24][25] We define the current state of pediatric research activity for neuropsychiatric disease, including the underrepresentation of certain drug classes and conditions. Specifically, we determine the proportion of clinical drug trials for neuropsychiatric conditions seeking to expand the evidence base for children and compare pediatric and adult research on these conditions.…”