RESUMEN

Stimulant medication is known to cause transient weight loss and slowing down of growth, but whether it delays physical maturation is unclear. We studied growth and bone age over the first 3 years of treatment in children with attention-deficit/hyperactivity disorder (patients) compared with healthy siblings (controls). Bone age was estimated blindly by two independent radiologists using Tanner and Whitehouse version 3. Dexamphetamine or methylphenidate was titrated and continued when clinically indicated. Forty out of 73 patients, together with 22 controls, completed the study. There were no significant growth differences between the two groups at baseline. Despite slower growth on treatment [5.1 cm/year, 95% confidence interval (CI): 4.7-5.5, vs. 6.3 cm/year, 95% CI: 5.7-6.8, P=0.002; and 2.7 kg/year, 95% CI: 2.1-3.3, vs. 4.4 kg/year, 95% CI: 3.5-5.3, P=0.005], the patients showed no significant maturational delay (RUS score: 49 U/year, 95% CI: 44-55, vs. 55 U/year, 95% CI: 47-63, P=0.27). A subgroup of patients underwent serial biochemistry and dual-energy X-ray absorptiometry, recording a significant reduction in fat (5.61±3.56-4.22±3.09 kg, P<0.001) and leptin (3.88±2.87-2.57±1.94 ng/ml, P=0.017). The pattern of change in height z-score over time was modified by the dose of medication (P for interaction=0.024). We found no medication effect on the rate of maturation, which was instead predicted by baseline leptin (P=0.035 controlling for age and sex).

Asunto(s)

Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Desarrollo Óseo/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/efectos adversos , Desarrollo Infantil/efectos de los fármacos , Dextroanfetamina/efectos adversos , Trastornos del Crecimiento/inducido químicamente , Metilfenidato/efectos adversos , Absorciometría de Fotón , Adiposidad/efectos de los fármacos , Factores de Edad , Antropometría , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/psicología , Biomarcadores/sangre , Estatura/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Estudios de Casos y Controles , Niño , Femenino , Trastornos del Crecimiento/sangre , Trastornos del Crecimiento/diagnóstico , Trastornos del Crecimiento/fisiopatología , Humanos , Leptina/sangre , Masculino , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

OBJECTIVE: To investigate the growth and pubertal attainment of boys with attention deficit hyperactivity disorder (ADHD) on stimulant medication. DESIGN, SETTING AND PARTICIPANTS: Longitudinal study of boys aged 12.00-15.99 years at recruitment in 2005-2011, with stimulant-treated ADHD for at least 3 years, attending three paediatric practices (subjects), compared with longitudinal data from 174 boys from the Nepean longitudinal study (controls). MAIN OUTCOME MEASURES: Subjects' growth parameters before treatment were compared with controls aged 7 or 8 years; growth parameters and longitudinal changes on treatment to ages 12.00-13.99 and 14.00-15.99 years were compared with controls reviewed at 13 and 15 years of age, respectively. The subjects' pubertal staging and height velocity were related to their treatment history. RESULTS: Sixty-five subjects were recruited; mean duration of treatment was 6.3 ± 1.9 years. At baseline, their growth parameters were not significantly different from those of the controls after adjusting for age. Compared with the controls, after adjusting for current age and baseline growth parameter z score, subjects aged 12.00-13.99 years had significantly lower weight and body mass index (P < 0.01), and those aged 14.00-15.99 years had significantly lower height and weight (P < 0.05). At 12.00-13.99 years of age, the subjects were comparable to the controls in their pubertal development adjusted for age, but those aged 14.00-15.99 years reported significant delay (mean Tanner stage, 3.6 for subjects v 4.0 for controls; P < 0.05). The dose of medication was inversely correlated with the height velocity from baseline to 14.00-15.99 years of age (P < 0.05). CONCLUSIONS: Prolonged treatment (more than 3 years) with stimulant medication was associated with a slower rate of physical development during puberty. To maintain adequate height velocity during puberty, we recommend keeping the dose as low as possible.

Asunto(s)

Desarrollo del Adolescente/efectos de los fármacos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Pubertad/efectos de los fármacos , Adolescente , Factores de Edad , Estatura/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/administración & dosificación , Estimulantes del Sistema Nervioso Central/efectos adversos , Niño , Relación Dosis-Respuesta a Droga , Humanos , Estudios Longitudinales , Masculino , Metilfenidato/administración & dosificación , Metilfenidato/efectos adversos , Metilfenidato/uso terapéutico

RESUMEN

OBJECTIVE: Children treated with stimulant medication for attention deficit hyperactivity disorder (ADHD) often lose weight. It is important to understand the implications of this during growth. This prospective study was designed to quantify the changes in body composition and markers of bone metabolism on starting treatment. METHODS: 34 children (29 boys) aged 4.7 to 9.1 years newly diagnosed with ADHD were treated with dexamphetamine or methylphenidate, titrating the dose to optimise the therapeutic response. Medication was continued for as long as clinically indicated. Body composition and bone density (dual-energy X-ray absorptiometry) were measured at baseline, 6 months and 3 years; changes were analysed in Z-scores based on data from 241 healthy, local children. Markers of bone turnover were measured at baseline, 3 months and 3 years. RESULTS: Fat loss of 1.4±0.96kg (total fat 5.7±3.6 to 4.3±3.1kg, p<0.001) occurred in the first 6 months. There were significant reductions over 3 years in the sex and height corrected Z-scores for lean tissue, bone mineral content, bone mineral density and ratio of central to total fat (-0.84±0.86, p=0.003; -0.55±0.31, p<0.0001; -0.41±0.28, p<0.0001 and -0.55±0.62, p=0.006 respectively). Propeptide of type I collagen indicated a significant reduction in bone turnover after 3 months (564±202 to 458±96ng/ml, p=0.019), which was fully recovered after 3 years (619±276ng/ml). CONCLUSIONS: Stimulant medication was associated with early fat loss and reduced bone turnover. Lean tissue including bone increased more slowly over 3 years of continuous treatment than would be expected for growth in height. There was long-term improvement in the proportion of central fat for height. This study shows that relatively minor reductions in weight on stimulant medication can be associated with long-term changes in body composition. Further study is required to determine the effects of these changes on adult health.