Randomized, placebo-controlled, crossover study of methylphenidate for attention-deficit/hyperactivity disorder symptoms in preschoolers with developmental disorders

Abstract

Objective: The aim of this study was to investigate the short-term efficacy and safety of methylphenidate (MPH) to treat attention-deficit/hyperactivity disorder (ADHD) symptoms in an understudied population of preschoolers with pervasive developmental disorder (PDD) or intellectual disability (ID).

Methods: Fourteen preschoolers with developmental disorders (DD, n = 14; PDD, n = 12; ID, n = 2) underwent MPH titration in a single-blind manner followed by a 4-week double-blind crossover phase. Each child was administered placebo for 2 weeks and "optimal dose" for 2 weeks. The primary outcome measure was the Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) ADHD subscale of the Conners' Parent Rating Scale-Revised (CPRS-R-DSM-IV-ADHD).

Results: MPH improved parent-rated ADHD symptoms of the preschoolers; 50% were rated as responders. The CPRS-R-DSM-IV-ADHD subscale was significant for the PDD subgroup (p = 0.005, Cohen d = 0.97) and marginally significant for the entire DD sample (p = 0.08, Cohen d = 0.50). Half of the preschoolers experienced side effects with MPH, including reports of increased stereotypic behavior, upset stomach, sleep-related difficulties, and emotional lability. One child discontinued during titration due to side effects.

Conclusion: The predominant direction of response in these preschoolers with both ADHD and PDD/ID favored MPH, even though the response was more subtle and variable than in older and typically developing children. Due to high rates of adverse effects, preschoolers should be monitored closely.

Figures

FIG. 1.

(A) Safety outcome: Side effect rating scale parent ratings (n = 14). The shaded portions of the columns indicate severe side effects. (B) Safety outcome: Spontaneously reported adverse events (n = 14). The shaded portions of the columns indicate moderate severity of the adverse events.