Stimulant Drug Response in the Predominantly Inattentive and Combined Subtypes of Attention-Deficit/Hyperactivity Disorder

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Abstract
This study compared the methylphenidate (MPH) dose-response profiles of children with the Predominantly Inattentive (PI) and Combined (CB) subtypes of attention-deficit/hyperactivity disorder (ADHD). It is the first such study to enroll a sample comprised exclusively of children, all but one of whom had no prior exposure to ADHD medications. The design was a double-blind crossover with 1-week exposures to placebo and low, medium, and high, fixed, three times daily (t.i.d.) dosage regimens of immediate-release MPH, administered in random order. Parents and teachers completed weekly behavioral questionnaires (Conners, Swanson, Kotkin, Agler, M-Flynn and Pelham Scale [SKAMP]) and a child psychiatrist provided weekly ratings of symptom severity (ADHD Rating Scale [ADHD-RS]), side effects (Side Effects Rating Scale), and a Clinical Global Impressions-Severity (CGI-S). In addition, laboratory measures of vigilance (Continuous Performance Test [CPT]) and resistance to cognitive interference (Stroop) were administered weekly. Twenty-five children (15 CB, 10 PI), who met rigorous diagnostic criteria for their ADHD subtype, completed the study. Groups did not differ on demographic variables or severity at baseline. Behavioral questionnaires and clinical ratings indicated significant improvement on MPH for both subtypes but no differences in response profiles of the two groups. Drug effects were predominantly linear for both subtypes. Effects of MPH were significant for the CPT, but not the Stroop, instrument with no differences between ADHD subtypes. Results support the clinical utility of MPH in the treatment of the PI subtype and provide no evidence of differences in response between the subtypes.