Attention deficit hyperactivity disorders (ADHD) in youth occur comorbidly with other psychiatric conditions approximately two thirds of the time. Major depressive disorder and dysthymic depression are common, occurring in as many as 40% of youth with ADHD. The comorbid occurrence of ADHD and depression (ADHD + Dep) may cause substantial long-term morbidity. While psychopharmacology is widely used to treat juvenile ADHD and/or depression, no research has established an efficacious treatment for ADHD + Dep, or for most other comorbid ADHD disorders. This five year Mentored Patient-Oriented Research Career Development Award (RCDA) will provide the candidate, a board certified child and adolescent psychiatrist, training to undertake pharmacological trials of youth with ADHD and comorbid disorders. The candidate has had extensive previous clinical experience and some research experience in the pharmacological treatment of juvenile ADHD + Dep. The RCDA will provide the candidate formal training in pharmacology, clinical trial design, and statistical analyses as well as the empirical assessment of juvenile ADHD, depression, and other comorbid psychopathology. The candidate will also receive training in ethical issues germane to juvenile psychopharmacology studies. Training will occur through a combination of formal coursework, guided readings, and consultation with mentors having relevant expertise. This training will be applied in a pharmacologic study of adolescents with ADHD and depression (major depression, dysthymia). The protocol will consist of a 2-week washout/observational period, then an 8-week randomized, placebo-controlled trial (RCT) to determine the efficacy of bupropion SR. Then a 24-week open label continuation phase will be used to determine if treatment response and tolerability persist. Exploratory analyses will assess correlations of initial treatment response with both pharmacological variables (plasma levels of bupropion and its metabolites; noradrenergic and dopaminergic effects as estimated by reuptake blockade of rat synaptosomes) and psychosocial variables (baseline psychopathology and psychosocial impairment). The candidate' s training and research experiences during the RCDA will enable him to pursue larger, more scientifically rigorous pharmacologic trials of youth with ADHD and depressive or other comorbid psychopathology.
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