Although current medication therapies ameliorate ADHD behavioral symptoms, problems with inadequateresponse or tolerability are common. Most perplexing, in consideration of ADHD-related cognitive deficitsand in spite of several hundred studies demonstrating acute behavioral response to stimulants, is the failureof many decades of research to demonstrate long-term, stimulated-related enhancements in learning. Thismanifest inadequacy of current therapies highlights the potential importance of developing treatments thatspecifically remediate executive function deficits as an important path to improve outcome.Neurochemical influences on cognitive functions in ADHD are complex. The over-arching premise of thisproject is that optimal behavioral and cognitive responses are possible with treatments that robustly enhanceboth dopamine (DA) and norepinephrine (NE). Our goal is to test the short-term efficacy of a combinationpharmacotherapy, derived from translational research and clinical observations, against standard stimulantmonotherapy on both symptom and cognitive endpoints. In addition, a novel aspect of the study will be totest prospectively whether a dual benefit on both behavior and cognition predicts clinically significantimprovements in learning over longer-term treatment. Lastly, based upon our preliminary data andhypothesized mechanisms of treatment response, the proposed study will examine the potential ofelectroencephalography (EEC) in predicting optimal long-term benefit. The clinical trial will enroll 180children and adolescents with ADHD-Combined Type in an active-controlled randomized parallel group studytesting the comparative efficacy of guanfacine (GUAN), methylphenidate (MPH), and combinationGUAN/MPH on ADHD symptoms and clinical response rates. Improvements in cognition during the acutetreatment phase will predict greater academic achievement over the 12 month maintenance period.The project will represent an initial scientific investment in a new phase of translational treatment researchon cognition in developmental psychopathologies. The designs and methodology tested in the proposed trialwill serve as a platform for testing other interventions.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Special Emphasis Panel (ZMH1-ERB-A (01))
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University of California Los Angeles
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Sturm, Alexandra; Rozenman, Michelle; Piacentini, John C et al. (2018) The Effect of Neurocognitive Function on Math Computation in Pediatric ADHD: Moderating Influences of Anxious Perfectionism and Gender. Child Psychiatry Hum Dev 49:822-832
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