COMMENTARY

The Long-term Safety of Stimulant Treatment

Thomas Spencer, MD

Disclosures

July 30, 2003

In This Article

Introduction

This column will review and synthesize the recent literature on 3 areas of concern in chronic stimulant treatment: effects on growth, tics, and cardiovascular parameters.

There have been longstanding concerns about growth deficits in children with ADHD. Although early studies showed associations between stimulant treatment and growth deficits in ADHD children, uncertainties remain as to their clinical significance and permanence.

Growth deficits in height and weight were examined in 124 ADHD male children and adolescents and 109 controls using appropriate correction by age and parental height measures.[1] Small but significant differences in height (2.1 cm age-corrected) were identified between ADHD children and controls. However, height deficits were evident in early- but not late-adolescent patients with ADHD and were unrelated to use of psychotropic medications. There was no evidence of weight deficits in ADHD children relative to controls, and no relationship between measures of malnutrition and short stature was identified. We found no evidence of delayed pubertal development. These results suggest that ADHD may be associated with temporary deficits in growth-in-height through mid-adolescence that may normalize by late adolescence.

In this sample, 89% of ADHD children had received pharmacologic treatment at some time in their life. Over the preceding 2 years, 45% had been treated with stimulants at an average daily dose of methylphenidate (or its equivalent) of 38 +/- 24 mg/day. However, observed height deficits were only evident in early adolescence and were unrelated to stimulant treatment. ADHD children in our study were slightly heavier than the normal population and had no evidence of stimulant-associated growth-in-weight suppression. These results suggest that ADHD in boys may be associated with temporary deficits in growth-in-height that are mediated by ADHD and not its treatment.

We conducted a parallel analysis[2] in a large sample of ADHD girls (n = 124) and female controls (n = 116). No deficits in age-adjusted height or age- and height-adjusted weight were detected in ADHD girls. Also, we found no association between growth measurements and psychotropic treatment, malnutrition, short stature, pubertal development, or family history of ADHD.

In this study, no meaningful differences in any height measurement were detected between psychopharmacologically treated (either lifetime or in the past 2 years) and untreated ADHD girls. Medicated ADHD girls were consistently taller and heavier than their nontreated counterparts on every height and weight measure examined. These data suggest that no growth deficits appear to be associated with ADHD or its treatment in females. These findings add to a growing literature supporting the notion that stimulant treatment does not have an adverse impact on ADHD children's growth and development.

OROS MPH (Concerta)

Recently, a study[3] was conducted on the growth effects of long-term once-daily OROS MPH treatment in 237 children with ADHD followed for up to 21 months. Children with ADHD (aged 6-13 years) received 18, 36, or 54 mg of once-daily OROS MPH. After an initial decrease in weight, weight increased from baseline (33.4 kg) to month 21 (39.5 kg). Age-specific weight z-scores revealed a slight loss of weight over time relative to the normal population. Mean absolute height increased consistently throughout the study from 136.2 cm at baseline to 146.1 cm at month 21. Age-specific height z-scores revealed a slight loss of height over time relative to the normal population. Most of the small lag in height growth occurred in the first 9 months, suggesting that the rate of deficit slows with increasing time on medication. The mean height deficit at end point was only 0.52 cm. Overall, OROS MPH produced no clinically meaningful changes in height, and had minimal impact on weight in this sample of ADHD children.

Adderall XR)

In a recent study,[4] children with ADHD (n = 568; aged 6-12 years) received 10, 20, or 30 mg of once-daily mixed amphetamine salts XR for up to 24 months (258 completers). Height deficits were greater in the first 18 months (-1.8 cm) than over the last 6 months (-2.2 cm, cumulative). In subjects of greatest concern, those who were already short, there were negligible height deficits. The number of very short subjects (< 5% of population height) was not greater between baseline and end point (4.8% vs 2.4%).

While weight deficits were statistically significant, the sample was larger than the population average at baseline. The authors concluded that while growth parameters should be monitored in treated children, for the majority of children treated with mixed amphetamine salts XR, growth deficits should not be a clinical concern.

Despite these reassuring results, a small minority of ADHD children may have delays in growth. Until more is known, children on stimulants should be monitored for growth while on psychotropics.

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