Childhood attention-deficit/hyperactivity disorder (ADHD) has been associated with childhood and adult obesity, and stimulant use with delayed childhood growth, but the independent influences are unclear. No longitudinal studies have examined associations of ADHD diagnosis and stimulant use on BMI trajectories throughout childhood and adolescence.
We used longitudinal electronic health record data from the Geisinger Health System on 163 820 children ages 3 to 18 years in Pennsylvania. Random effects linear regression models were used to model BMI trajectories with increasing age in relation to ADHD diagnosis, age at first stimulant use, and stimulant use duration, while controlling for confounding variables.
Mean (SD) age at first BMI was 8.9 (5.0) years, and children provided a mean (SD) of 3.2 (2.4) annual BMI measurements. On average, BMI trajectories showed a curvilinear relation with age. There were consistent associations of unmedicated ADHD with higher BMIs during childhood compared with those without ADHD or stimulants. Younger age at first stimulant use and longer duration of stimulant use were each associated with slower BMI growth earlier in childhood but a more rapid rebound to higher BMIs in late adolescence.
The study provides the first longitudinal evidence that ADHD during childhood not treated with stimulants was associated with higher childhood BMIs. In contrast, ADHD treated with stimulants was associated with slower early BMI growth but a rebound later in adolescence to levels above children without a history of ADHD or stimulant use. The findings have important clinical and neurobiological implications.
Comments
Stimulants in patients with ADHD and obesity: harmful of beneficial?
We congratulate the authors of the article "Attention Deficit Disorder, Stimulant Use, and Childhood Body Mass Index Trajectory" for developing a study involving two very important conditions: ADHD and obesity.
However, we disagree with some of the points raised by the authors, and would like to add some contributions to the discussion.
Firstly, the authors did not exclude from their sample patients who have made use of other psychotropic drugs and 51.4% of the sample made use of such drugs in addition to the stimulant medication. Moreover, it is not clear if, when the stimulant was suspended, the patients continued to use other psychotropic drugs. Considering that most of these drugs favor weight gain[1], we think that it is not possible to affirm that the increase in BMI in adolescence can be attributed to the prior use of stimulant or to its suspension.
Our group has been researching the association of ADHD and obesity in patients in a public hospital in Sao Paulo, Brazil.
We followed 156 patients under methylphenidate treatment, of which 96 had comorbidities or used medications that could affect the nutritional status. The remaining 60 were all diagnosed with ADHD and drug treatment- naive, and formed a sample with the following characteristics at the beginning of treatment: mean age of 9; 51.7% normal weight; 33.3% overweight; and 15.0% obese. The 'end of treatment' was registered when the stimulant was suspended or when another drug that could affect the nutritional status was associated.
We compared the mean BMI z-score of the sample at the end of treatment (0.606) to the one at baseline (0.933), and found a statistically significant reduction.
Breaking down the analysis by BMI level, we found that 40% of the patients who were initially overweight had normal weight in the end of treatment. Similarly, among obese patients, 33% eventually became overweight. On the other hand, among the 31 patients who began the treatment with normal weight, only one crossed the thinness threshold.
Afterwards, we compared the z-scores for height, and found no statistically significant impact of the methylphenidate (z-score of 0.086 in the end of treatment versus 0.033 in the beginning).
Our data suggest that treatment of ADHD with stimulants can both help in the control of the symptoms of ADHD and improve the nutritional status, with the additional benefit of not affecting height.
We believe that the effect of stimulants on nutritional status is not limited to its anorectic properties. The use of the medication probably helped to reduce the symptoms of impulsiveness and lack of attention, leading to a lower caloric intake and a 'more organized' dietary pattern, which may have helped individuals who were overweight or obese to lose weight.[2,3]
References: 1.Hasnain M, Vieweg WV. Weight considerations in psychotropic drug prescribing and switching. Postgrad Med. 2013;125:117-29. 2.Barkley RA, McMurray MB, Edelbrock CS, Robbins K. Side effects of methylphenidate in children with attention deficit hyperactivity disorder: a systemic, placebo-controlled evaluation. Pediatrics. 1990;86:184-192 3.Levy LD, Fleming JP, Klar D. Treatment of refractory obesity in severely obese adults following management of newly diagnosed attention deficit hyperactivity disorder. Int J Obes (Lond). 2009;33:326-34
Conflict of Interest:
Dr. Casella: advisory board and speaker of Janssen Cilag, Novartis and Shire. Dr. Ferraro and Dr. Granato: Nothing to declare
Overweight or Overstated?
Dear Editor,
In their longitudinal study looking at BMI trajectories for children with ADHD on stimulant medication compared to children with ADHD not medicated and control group Schwartz et al has managed to analyse a very large cohort. Despite the large numbers analysed we question the clinical relevance and the impact of the conclusions drawn.
The study data is obtained from a very specific population: children seen by private primary physicians in Pennsylvania. The diagnosis of ADHD has been made on basis of ICD only and it is unclear how this relates to DSM-V criteria. Children had a minimum of one BMI measurement and a maximum of 13, with the likelihood of children with weight problems (e.g. underweight or obese) having more frequent measurements performed, skewing the data and potentially biasing the results. The authors used untransformed BMI values instead of z-scores or centiles referenced from an external population, reporting that this would give more precise results. Z-scores, however, can be appropriately used to compare between group means and to model relative weight trajectories longitudinally1 . They can also provide for greater interpretability of results in clinical practice.
The rationale to exclude children less than 2 years of age because of difficulties obtaining height was puzzling. We also query the group of children who received stimulant medication without a diagnosis of ADHD. This included 1684 children, which raises the question if the diagnosis was underestimated by 12%. When looking at the BMI rebound effect in later life in children on stimulant medication, information regarding the effect of continuation or cessation of treatment on BMI has not been reported or discussed.
Although a standard linear mixed effects model was used to analyse the data, the presentation and interpretability of the results was far from clear. The results mainly relied on the significance or otherwise of the p-values estimated from the fitted model with confidence intervals and effect sizes (difference between BMI values by group) largely ignored. A major issue with interpreting p-values alone is that with such large numbers in the cohort analysed, a small but statistically significant difference can be easily achieved, even when the clinical effect or significance is minimal to non-existent2. Thus, in this context, confidence intervals of the effect sizes provide much needed information. Alternative statistical approaches, such as a Bayesian approach, which directly evaluates the magnitude of the effect size could also have been used. As relatively little data was available at later ages, caution should also be exercised in drawing conclusions from the fitted model (or fitted line) for this period.
From a clinicians point of view, we were unable to draw any clear clinical implications from the data. There was no discussion regarding possible implications or preventative management measures to address the proposed obesity issues in children with ADHD and rebound effect in later life.
Reference 1) Body Mass Index in children and adolescents; A Must, SE Anderson; International Journal of Obesity (2006) 30, 590594 2) Armitage, P. Berry, G. & Matthews, J N S, Statistical Methods in Medical Research. 4th Edition. John Wiley and Sons, Oxford.
Conflict of Interest:
None declared