A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder.

Antidepressants are standardly used to treat moderate to severe symptoms of depression and/or anxiety in youth but may also be associated with rare but serious psychiatric adverse events such as irritability, agitation, aggression, or suicidal ideation. Adverse events are especially common in youth with a family history of bipolar disorder (BD) who are at heightened risk for dysfunction in neurobiological systems that regulate emotion and arousal. To further understand this phenomenon, this study will examine (a) baseline risk factors associated with dysfunctional arousal in a sample of youth at high-risk for BD treated with or without an antidepressant, (b) whether antidepressant-related changes in arousal are mediated by changes in prefrontal-limbic circuitry, and (c) whether pharmacogenetic factors influence antidepressant-related changes in arousal. High-risk youth (aged 12-17 years with moderate to severe depressive and/or anxiety symptoms and at least one first-degree relative with bipolar I disorder) will be randomized to receive psychotherapy plus escitalopram or psychotherapy plus placebo. Neuroimaging and behavioral measures of arousal will be collected prior to randomization and at 4 weeks. Samples for pharmacogenetic analysis (serum escitalopram concentration, CYP2C19 metabolizer phenotype, and HTR2A and SLC6A4 genotypes) will be collected at 8 weeks. Youth will be followed for up to 16 weeks to assess change in arousal measures.

The use of cognitive behavioral therapy in the treatment of resistant depression in adolescents.

Major depressive disorder often begins in adolescence, is chronic and recurrent, and heightens an individual's risk for major depressive disorder in adulthood. Treatment-resistant depression is a problem for a significant minority of adolescents. Few studies have examined treatments for treatment-resistant depression among adolescents, and even fewer have examined the use of cognitive-behavioral therapy as a monotherapy or in combination with pharmacological treatments. Mental health professionals have a strong interest in understanding what treatments are appropriate for adolescents who are treatment resistant. Preliminary evidence from current published trials indicates that the use of cognitive-behavioral therapy in combination with antidepressant medication yields the best outcome for treatment-resistant depression in adolescents. Secondary analyses also suggest that the utility of cognitive behavioral therapy can be increased by ensuring adolescents receive a therapeutic dose of treatment sessions (more than nine sessions) and the inclusion of two treatment components: social skills and problem solving training. Guidelines for clinicians as well as areas for future research are discussed.