Methylphenidate Treatment of ADHD in Preschoolers

March 1, 2007

Despite the increased use of methylphenidate in preschoolers with attention deficit/hyperactivity disorder (ADHD), few data are available regarding the efficacy and safety of methylphenidate in this population. Methylphenidate has been approved by the FDA for the treatment of ADHD in children aged 6 years or older. A recent large-scale, controlled trial of methylphenidate for the treatment of preschoolers with ADHD provides clinically relevant and greatly needed information for clinicians who treat these children.

Despite the increased use of methylphenidate in preschoolers with attention deficit/hyperactivity disorder (ADHD), few data are available regarding the efficacy and safety of methylphenidate in this population. Methylphenidate has been approved by the FDA for the treatment of ADHD in children aged 6 years or older. A recent large-scale, controlled trial of methylphenidate for the treatment of preschoolers with ADHD provides clinically relevant and greatly needed information for clinicians who treat these children.

The Preschool ADHD Treatment Study (PATS) was an NIMH-funded, 6-center, controlled trial to evaluate the efficacy and safety of methylphenidate for preschool children with ADHD. 1,2 The ages of children who participated in the study ranged from 3 to 5.5 years. One hundred eighty-three children participated in the study, which consisted of 4 phases: a 1-week, open-label, lead-in phase (n = 183); a 5-week, double-blind, placebo-controlled phase (n = 165); a 5-week, double-blind, parallel phase (n = 114); and a 10-month, open-label maintenance phase (n = 140). Methylphenidate immediate-release (IR) was administered on a thrice-daily schedule.

Overall, the results showed that compared with placebo, there was a sig- nificant decrease in children's ADHD symptoms with methylphenidate at dosages of 2.5 mg, 5 mg, and 7.5 mg tid. The effect sizes for these dosages ranged from 0.4 to 0.8. There were no significant differences found between placebo and methylphenidate at a dosage of 1.25 mg tid. The mean optimal methylphenidate-IR total daily dose was 14.2 mg (0.7 mg/kg).

Clinical Findings The researchers in the PATS reported a number of clinically important findings.

2-4

Dosing
Based on the data, it was suggested that initial treatment with methylphenidate begin at low dosages. The recommended starting dosage was methylpheni- date-IR at 2.5 mg bid, with an increase to 7.5 mg tid over 1 week.

Safety
The 5 most commonly reported adverse effects were emotional outbursts, difficulty in falling asleep, repetitive behavior/thoughts, decreased appetite, and irritability. One serious adverse event of a seizure was rated by the treating physician as possibly being associated with methylphenidate treatment. Eleven percent of preschoolers who received methylphenidate discontinued study treatment because of adverse events. Emotionality and irritability were frequent reasons for discontinuation.

Discontinuation of methylphenidate treatment because of intolerable adverse effects occurred in more preschool-aged children (11%) in the PATS than in school-aged children (fewer than 1%) in the Multimodal Treatment Study of Children With ADHD. 5

For some preschoolers, the irritability and emotionality diminished over time. The investigators found that adverse effects such as appetite reduction and difficulty in sleeping remained stable. They recommended that these side effects be managed by dose reduction, by the child eating breakfast before receiving medication, and by parents giving healthy snacks to the child before bedtime.

Cardiovascular effects
Blood pressure and pulse increased for children during the course of the study, but there were no significant differences found between preschoolers treated with placebo or methylphenidate on blood pressure and pulse measures. Five children had a 1-time episode of elevated systolic blood pressure and pulse. However, no child met criteria for clinically significant hypertension.

Although concerns have been raised regarding the cardiovascular safety of methylphenidate in children, the PATS safety data did not find clinically significant cardiovascular effects.

Growth
After starting treatment with methylphenidate-IR, the mean growth rate slowed for preschoolers. For the 95 children who continued to take medication during the maintenance phase, there was a reduction in both expected height and weight gain.

The investigators recommend that parents be informed that treatment of their preschoolers with methylphenidate may result in a reduction in growth rate of approximately 20% (1.38 cm) for height and approximately 55% (1.32 kg) for weight over a 1-year treatment period. They further recommended that height and weight be assessed 3 or 4 times every year for preschool-aged children who are being treated with stimulant medication.

Conclusion
The findings from the PATS provide welcome information about efficacy, safety, and tolerability of methylphenidate in preschool children with ADHD. This rigorously designed and carefully executed study provides a wealth of clinical information to clinicians who treat preschoolers with ADHD.

References:

References1. Kollins S, Greenhill L, Swanson J, et al. Rationale, design, and methods of the Preschool ADHD Treatment Study (PATS). J Am Acad Child Adolesc Psychiatry. 2006; 45:1275-1283.
2. Greenhill L, Kollins S, Abikoff H, et al. Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry. 2006;45:1284-1293.
3. Wigal T, Greenhill L, Chuang S, et al. Safety and tolerability of methylphenidate in preschool children with ADHD. J Am Acad Child Adolesc Psychiatry. 2006;45: 1294-1303.
4. Swanson J, Greenhill L, Wigal T, et al. Stimulant-related reductions of growth rates in the PATS. J Am Acad Child Adolesc Psychiatry. 2006;45:1304-1313.
5. MTA Cooperative Group. A 14-month randomized clinical trial of treatment strategies for attention-deficit/ hyperactivity disorder. Multimodal Treatment Study of Children With ADHD. Arch Gen Psychiatry. 1999;56: 1073-1086.