Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD
Laurence Greenhill1, Scott Kollins2, Howard Abikoff2
1Dr. Greenhill and Posner, Mr. Davies, Mr. Cooper, Ms. Skrobala, and Ms. Chuang are with the New York State Psychiatric Institute/Columbia University; Dr. Kollins is with Duke University, Durham, NC; Dr. Abikoff is with the New York University Child Study Center, New York; Dr. Riddle is with Johns Hopkins University, Baltimore; Dr. Ghuman is with the University of Arizona, Tucson; Dr. Cunningham is with McMaster University, Hamilton, Ontario, Canada; Drs. McCracken and McGough are with the University of California, Los Angeles; Drs. Swanson, T. Wigal, and S. Wigal are with the University of California, Irvine; and Mr. Cooper is also with the Nathan Kline Institute, Orangeburg, NY; Dr. Vitiello is with the National Institute of Mental Health, Bethesda, MD..
Insights
Immediate-release methylphenidate (MPH-IR) significantly reduced attention-deficit/hyperactivity disorder (ADHD) symptoms in preschoolers aged 3-5.5 years. Doses of 2.5, 5, and 7.5 mg three times daily showed efficacy, though effect sizes were smaller than in older children.
Area of Science:
- Pediatric Psychiatry
- Neuroscience
- Pharmacology
Background:
- The Preschool ADHD Treatment Study (PATS) investigated the efficacy and safety of methylphenidate immediate-release (MPH-IR) in young children.
- Attention-deficit/hyperactivity disorder (ADHD) diagnosis and treatment in preschoolers present unique challenges due to developmental variability.
Discussion:
- MPH-IR demonstrated statistically significant reductions in ADHD symptom severity across multiple rating scales in preschoolers.
- The optimal dosage varied, with significant effects observed at 2.5 mg, 5 mg, and 7.5 mg administered three times daily.
- Effect sizes for MPH-IR in preschoolers were smaller compared to those reported for school-aged children, suggesting potential differences in medication response.
Key Insights:
- Immediate-release methylphenidate (MPH-IR) is effective in reducing ADHD symptoms in children aged 3 to 5.5 years.
- The study established effective MPH-IR dosage ranges for this young population.
- While effective, the magnitude of symptom reduction was less pronounced than in older children.
Outlook:
- Further research may explore long-term outcomes and alternative formulations for preschoolers with ADHD.
- Investigating predictors of treatment response could personalize MPH-IR therapy.
- Comparative studies with other ADHD medications in this age group are warranted.
Objective:
The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six-center, randomized, controlled trial to determine the efficacy and safety of immediate-release methylphenidate (MPH-IR), given t.i.d. to children ages 3 to 5.5 years with attention-deficit/hyperactivity disorder (ADHD).
Method:
The 8-phase, 70-week PATS protocol included two double-blind, controlled phases, a crossover-titration trial followed by a placebo-controlled parallel trial. The crossover-titration phase's primary efficacy measure was a combined score from the Swanson, Kotkin, Atkins, M-Flynn, and Pelham (SKAMP) plus the Conners, Loney, and Milich (CLAM) rating scales; the parallel phase's primary outcome measure was excellent response, based on composite scores on the Swanson, Nolan, and Pelham (SNAP) rating scale.
Results:
Of 303 preschoolers enrolled, 165 were randomized into the titration trial. Compared with placebo, significant decreases in ADHD symptoms were found on MPH at 2.5 mg (p<.01), 5 mg (p<.001), and 7.5 mg (p<.001) t.i.d. doses, but not for 1.25 mg (p<.06). The mean optimal MPH total daily dose for the entire group was 14.2 +/- 8.1 mg/day (0.7+/-0.4 mg/kg/day). For the preschoolers (n=114) later randomized into the parallel phase, only 21% on best-dose MPH and 13% on placebo achieved MTA-defined categorical criterion for remission set for school-age children with ADHD.
Conclusions:
MPH-IR, delivered in 2.5-, 5-, and 7.5-mg doses t.i.d., produced significant reductions on ADHD symptom scales in preschoolers compared to placebo, although effect sizes (0.4-0.8) were smaller than those cited for school-age children on the same medication.
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