Does stimulant pharmacotherapy of ADHD affect height?
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The use of stimulant medications has been an integral aspect for the pharmacotherapy of ADHD for more than 50 years. Numerous published studies have documented their efficacy to reduce symptoms of ADHD in children older than age 4 years. As with any medication, however, adverse effects occur, and these adverse effects must be balanced against the medication’s benefit for each individual patient. The potential for a negative adverse effect on growth from stimulant medications has been discussed in the literature for years.
Numerous stimulant (methylphenidate- based, amphetamine-based) medication dosage forms and products are now available, and recent years have seen an increase in the variety of pediatric-friendly products. Stimulant use may result in appetite suppression, headache, abdominal pain and sleep difficulties. Adverse effects on growth have also been evaluated.
MTA study and follow-up studies
A landmark study documenting the efficacy of various treatment strategies for ADHD was published in 1999, by the MTA (Multimodal Treatment Study of ADHD) Cooperative Group. The MTA study evaluated medication and behavioral treatments in children aged 7 to 10 years (n = 579) with combined-type ADHD. Researchers randomly assigned participants to one of four groups: intensive multicomponent behavior therapy; intensive medication management; a combination of these therapies; and self-selected community care. They conducted medication management with immediate-release methylphenidate. Treatment was continued and evaluated for 14 months, and at study conclusion, study participants who received combination therapy and intensive medication management demonstrated the greatest improvement. However, a growth deficit difference of –1.44 cm (equivalent to –1.23 cm per year) was demonstrated between the medication management and behavior management groups. Since publication of the original MTA study, more than 100 additional publications have evaluated data from long-term treatment effects on these study participants.
In a 24-month follow-up evaluation of the initial MTA study (ie, 10 months after the 14-month study concluded), researchers assessed 540 of the 579 subjects for continuation and/or change (off random assignment) to stimulant medication use. At the conclusion of the MTA study, participants were nonrandomly allocated into four naturalistic groups — Med/Med, a subgroup that consistently reported medication use; Med/NoMed, a subgroup of participants who reported stopping medication; NoMed/Med, a subgroup that reported starting medication; and NoMed/NoMed, a subgroup of participants who never reported medication use — based upon use of stimulants at two time points: 14 months (initial study conclusion) and 24 months. Researchers evaluated patterns of medication use for changes in treatment effectiveness and growth.
This follow-up study demonstrated that the Med/Med group, had reduced growth suppression compared with the NoMed/NoMed group, –0.87 cm over the 10-month follow-up phase. In the 3-year follow-up study of MTA study participants, naturalistic subgroups also were formed, based on stimulant medication use across the initial study and follow-up periods. These groups were described as not medicated; newly medicated; consistently medicated; and inconsistently medicated (total, n = 370). Z height and z weight scores (deviation from the population norm using standard unit deviation unit measurements) were significantly (negatively) affected by stimulant medication use, primarily because of a difference in the newly medicated and not medicated subgroups. The initially stimulant-naive subgroups had z scores significantly greater than 0 at baseline (ie, greater normative growth). At 36 months, the newly medicated group demonstrated a decreased growth of 2 cm in height and 2.7 kg in weight — less than the nonmedicated subgroup. This reduction in growth rate was maximal in the first year, less in the second year and absent in the third year. Thus, growth rebound from consistent stimulant use, as has been suggested by other researchers, was not evident.
In the most recently published long-term follow-up analysis of the MTA study, researchers monitored treatment with stimulants until age 18 years. This was an observational analysis of 515 participants with eight assessments at 2 to 16 years after baseline (this includes follow-up into early adulthood), with 289 additional participants (258 without ADHD), recruited from the same schools as the ADHD cases, added as a local normative comparison group. Naturalistic subgroups were based on long-term stimulant use: consistent, inconsistent and negligible. For adult height, the ADHD group was –1.29 +/– 0.55 cm vs. the local normative comparison group. Comparisons of the naturalistic subgroups revealed a decreased height of 2.55 +/– 0.73 cm when subjects in the consistent or inconsistent subgroups were compared with subjects in the negligible group. Additionally, a growth reduction of 2.36 +/– 1.13 cm was demonstrated in the consistent subgroup as compared with the inconsistent subgroup. Thus, consistent use of stimulant medication was associated with suppression of adult height.
Additional long-term studies
Some additional long-term follow-up studies have reached differing conclusions from the studies described earlier. In a description of two identical case-control studies of children with and without ADHD (n = 261), researchers analyzed growth data at 10- to 11-year follow-ups. They used linear growth curve models to estimate change in height from stimulant medication use. Neither ADHD nor the use of stimulant medication were associated with differences in growth. A case-control study evaluated ADHD cases (n = 340) and controls (n = 680) from a birth cohort of children born between 1976 and 1982 (n = 5,718) in Minnesota. The study included a retrospective phase and a prospective follow-up of cases into adulthood. Researchers analyzed stimulant medication use and height data from case medical records. They assessed height z scores at the beginning, end and 2 years after the end of treatment, and estimated peak height velocity age and magnitude. Neither ADHD nor stimulant treatment was associated with differences in peak height velocity or final adult height.
Literature reviews
Several literature reviews have addressed the effects stimulant pharmacotherapy may have on growth and height attainment. Farone and colleagues published a quantitative analysis of 20 longitudinal studies about growth in children treated with stimulants for ADHD and concluded that the data demonstrate a statistically significant, yet small, delay in height and weight due to stimulant use. Furthermore, these growth deficits may be dose-dependent, and treatment cessation may result in growth normalization. In a recently published review, Richardson and colleagues described numerous studies that evaluated the potential for growth adverse effects from stimulant therapy of ADHD. These studies are equivocal — some studies demonstrated short-term (ie, 2 to 3 years) growth deficits, some longer term studies suggested a growth reduction of final adult height, and yet other studies concluded that negative effects upon height do not occur.
AAP guidelines
The AAP published an updated clinical practice guideline for the diagnosis, evaluation and treatment of ADHD in children and adolescents in 2019. The guideline described the results of the 3-year MTA study, noting a growth reduction of 1 to 2 cm from predicted adult height, with a relationship to higher dose and consistent treatment, and without rebound growth.
Conclusions
ADHD is one of the most common neuropsychiatric disorders of the pediatric population. The use of stimulant medications has been extensively evaluated in the published literature. Yet, controversies over their adverse effect profile remain. The accumulative data appear to suggest that stimulants have the potential to suppress appetite and growth, including weight and height. Most data indicate that this height suppression is relatively mild — about 1 to 3 cm. The clinical significance of this is, of course, patient-specific and debatable. The effects of long-term stimulant use throughout childhood and adolescence on final adult height are not fully known. Some data suggest that growth suppression is dose- and treatment duration-related, which seems logical. Study data are equivocal because of differences in study methodology and study subject selection, including group selection bias. As with all medications, a benefit-to-risk analysis for each treated child is important. Methods to decrease medication exposure are additionally important to consider — use of the lowest stimulant dose possible to adequately control symptoms, and a combination of stimulant pharmacotherapy and nonpharmacotherapy approaches (ie, behavioral management strategies) because lower stimulant doses in combination can be equally effective as higher doses. Nonpharmacotherapy strategies may also include enhanced nutritional and caloric intake to minimize growth deficits. There does not appear to be differences in growth effects related to specific classes of stimulants or agents. For successful ADHD treatment, frequent monitoring and follow-up for growth (height measurement) and efficacy (symptom reduction) is also important.
- For more information:
- Edward A. Bell, PharmD, BCPS, is a professor of pharmacy practice at Drake University College of Pharmacy and Health Sciences and Blank Children’s Hospital and Clinics in Des Moines, Iowa. He also is a member of the Infectious Diseases in Children Editorial Board. Bell can be reached at ed.bell@drake.edu.
Disclosure: Bell reports no relevant financial disclosures.
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