JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 18, Number 3, 2008 © Mary Ann Liebert, Inc. Pp. 237–247 DOI: 10.1089/cap.2007.0140 Unexpected Effects of Methylphenidate in Attention- Deficit/Hyperactivity Disorder Reflect Decreases in Core/Secondary Symptoms and Physical Complaints Common to All Children Mark D. Rapport, Ph.D., Michael J. Kofler, M.S., Maria M. Coiro, Ph.D., Joseph S. Raiker, B.S., Dustin E. Sarver, B.A., and R. Matt Alderson, M.S. Abstract Hypotheses concerning unexpected, psychostimulant-related effects reported in previous studies were exam- ined by separating behavioral/physical complaints highly specific to methylphenidate (MPH) from those that (a) may mimic core/secondary symptoms of the disorder, or (b) are commonly reported by unmedicated chil- dren in the general population. Sixty-five children with attention-deficit/hyperactivity disorder (ADHD) par- ticipated in a double-blind, placebo-controlled, within-subject (crossover) experimental design and received a placebo and four MPH doses in counterbalanced order following baseline assessment. Behavioral and physi- cal complaints were significantly higher under baseline relative to placebo and the four immediate-release MPH conditions (5 mg, 10 mg, 15 mg, and 20 mg) across three symptom categories: ADHD core/secondary symp- toms; symptoms commonly reported in the general population, including unmedicated children with ADHD; and symptoms highly specific to MPH. No significant differences were found among active drug conditions. Past unexpected findings of psychostimulant effects in ADHD may be due to the inclusion of scale items that reflect core/secondary features of ADHD and normally occurring behavioral/physical complaints in children. 237 A TTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD) is a complex and chronic disorder of brain, behavior, and development whose behavioral and cognitive consequences pervade multiple areas of functioning. Core features of the disorder involve difficulties with attention, impulsiveness, and hyperactivity (APA 2000) and are hypothesized to affect behavioral and cognitive functioning to the extent that the latter are dependent upon the former for successful execu- tion (Rapport et al. 2001). Treatment of ADHD traditionally involves using behavior or pharmacological therapy alone or in combination (for reviews, see Chronis et al. 2004; Con- ners et al. 2001; Jensen 1999). Pharmacological interventions (and particularly the psy- chostimulants), however, are generally considered more cost effective and have the added benefit of affecting both be- havioral and cognitive domains throughout the day without the specific programming and oversight required by behav- ior therapy (DuPaul and Eckert 1997; Gittelman-Klein and Klein 1976; MTA Cooperative Group 1999). Methylphenidate (MPH) is by far the most commonly prescribed pharmaco- logical treatment for ADHD (Faraone et al. 2002; Grcevich et al. 2001; Jensen 1999; Swanson and Volkow 2002), and its reputation is well deserved based on traditional benchmarks, including breadth of effectiveness and overall response rate among affected individuals (Barkley, 2006; Denney and Rap- port 2001; Rapport et al. 1994). As with all therapies, how- ever, treatment emergent symptoms can and do occur. Side effects associated with psychostimulant treatment are well documented in the literature and fall primarily into one of three categories: cardiovascular effects (i.e., heart rate, blood pressure), physical effects (i.e., weight and growth), and physical and behavioral complaints. Recent reviews in- dicate that cardiovascular and physical effects associated with psychostimulant therapy are usually transient, dose de- pendent, readily resolved by discontinuing therapy, and fail to remain significant in long-term follow-up studies (Rap- port and Moffitt 2002). Psychostimulant-related physical and behavioral complaints, on the other hand, have received re- newed interest secondary to the unexpected effects reported in recent, well-controlled studies. For example, parents Department of Psychology, University of Central Florida, Orlando, Florida