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• W4254910748 abstract "Although psychostimulants have been used safely in clinical medicine for more than 60 years, they do have side effects. The most common, which usually are transient, include headaches, abdominal discomfort, mild-to-moderate appetite suppression, irritability, “daze-effect,” insomnia, tachycardia, and mild hypertension. Particularly controversial has been the concern that suppression of growth may be associated with psychostimulant use. The possible relationship of growth to attention-deficit/hyperactivity disorder (ADHD) may be mediated by several potential mechanisms, including direct effect on cartilage, altered central nervous system growth factors, and altered hepatic growth factors, all of which may be either medication-induced or disorder-specific. Additionally, children who experience a chronic decrease in appetite may be at risk for growth suppression.Among the first of many researchers attempting to shed light on the relationship between psychostimulants, ADHD, and growth deficits were Safer, Allen, and Barr (1972), who studied 29 children classified as being “hyperactive.” They found that moderate daily doses (10 to 15 mg) of dextroamphetamine (DEX) and moderate-to-high daily doses (30 to 40 mg) of methylphenidate (MPH) were associated with suppression of weight gain, with variable effects on height velocity. Notably, children treated with 20 mg or less of MPH showed significantly less suppression than those receiving DEX or higher doses of MPH. After the cohort was divided into “drug holiday” and “drug continuation” groups over the summer, the gains in weight between the two groups differed substantially, with the nontreated (“holiday”) group gaining about twice as much weight as the group continued on stimulants. The authors proposed that a “rebound phenomenon” occurred during the summer months, probably linked to the return in appetite. Theirs is one of the only papers in the literature that actually recommends the use of MPH over DEX (most studies since have reported comparable efficacy for both medications and similarities in growth suppressive properties).In the late 1970s, a United States Food and Drug Administration advisory committee on psychiatric drug use in children found that temporaryslowing of growth may occur early (over the first 2 years) in treatment, but the effects on final adult height were minimal if the drugs were dosed properly. The committee also cited evidence for possible disorder-related growth delays, although it concluded “tentatively, that untreated hyperkinetic children are near normal in stature, weight, and skeletal maturity.” (A subtype of what is today referred to as ADHD then was known as the “hyperkinetic behavior syndrome of childhood.”) The review recommended longer-term studies and careful monitoring of growth and height during treatment for at-risk populations, such as those whose growth was delayed for age.One of the first longitudinal studies was performed by Klein and Mannuzza (1988), who followed a cohort of 61 stimulant-treated children who had ADHD through adolescence and into young adulthood. The average daily dose of stimulant (MPH) was 45 mg, and the range of treatment duration was 6 months to 5 years. They described a “growth-rebound phenomenon” upon cessation of medication therapy and ultimately found no significant difference in final height between the treated patients (n=61, ADHD) and the controls (n=99, nonADHD). Patients’ use of other psychotropic medications, as well as nonstandardized methods of height assessment, may have confounded their data. Still, this large-scale, prospective study showed evidence for important compensatory gains in both height and weight, even with prior treatment on higher MPH doses. Like Safer et al, this research group also had previously shown significant growth-rebound effects in a separate controlled study of 3-month MPH summer holidays.Later research has highlighted the phenomenon of pretreatment weight as a predictor of weight loss. Schertz et al (1996) found that heavier children (body mass index [BMI] >50th percentile) treated with either DEX or MPH tended to experience a decrease relative to their predicted BMI compared with thinner (BMI <50th percentile) children after adjusting for age, gender, and height.Spencer and colleagues (1998) found moderate height deficits in 124 referred boys who had ADHD compared with 109 control subjects. The deficits, however, were evident only in early adolescence and were not related to weight deficits, stimulant treatment, or timing of puberty. Further, they proposed that the delays in growth noted in some children early in treatment likely would normalize by late adolescence, even if treatment with stimulants were to continue throughout adolescence. These temporary delays, they postulated, are due to disorder-specific catecholamine dysregulation that may alter neuroendocrine function and lead to slow growth.One weakness in previous studies of ADHD and growth is that the comparison of growth deficits among children of different ages presents difficult methodologic problems, including the nonlinear relationship of height and age. Spencer et al were the first in the ADHD literature to use z scores to assess height variability. For children, this is a much more valid technique than averaged height measurements, which previously had been the norm. This group also controlled for parental height and for comorbidity with other mental disorders, an important consideration because short parents tend to have short children and illnesses such as anxiety and depression may be associated with short stature. Their findings for ADHD-affected children were consistent with the previous literature in that they identified small, but statistically significant deficits in height gain (average, 2.1 cm). Interestingly, they found no evidence of stimulant-associated deficits in weight gain, consistent with recent reports that weight and height suppression are independent in children who are treated with stimulants. However, 10% of ADHD-affected children (but only 1% of controls) are more than 2 standard deviations below the average height of the nonADHD controls. They concluded that an important subset of children may have marked delay in height gain that requires close follow-up with possible dose adjustments.Ultimately, the best way to differentiate disorder-related from medication-related effects would be to compare treated children who have ADHD with untreated children who also have ADHD, rather than with unaffected control subjects. The difficulty in instituting such a classically designed placebo-controlled clinical trial is not unique to ADHD. To deny empirically proven medication for ADHD over a sufficient time to document differences in final stature raises ethical concerns.Currently there are no specific recommendations regarding “drug holidays” from either the American Academy of Pediatrics or the American Academy of Child and Adolescent Psychiatry, other than that they should be used when clinically indicated. However, “holidays” are not routinely necessary for most children who are monitored closely. Until more long-term follow-up studies are completed examining the effects of stimulants on weight gain and ultimate height, many clinicians will continue to prescribe regular weekend and/or summer breaks from therapy. This approach represents currently acceptable practice, as long as adequate doses are used during treatment phases. Once the patient is stabilized on the appropriate dose, there should be follow-up every 1 to 3 months to assess dose adequacy, growth progress, cardiovascular parameters, and overall functioning. These guidelines apply to the majority of children whose ADHD is not complicated by accompanying conduct or oppositional disorders, learning disorders, mood or anxiety disorders, or other comorbid psychosocial problems. Children who have more complex diagnoses may require consultation with a psychiatrist or behavioral pediatrician for more extensive management.Clinical medicine isn’t easy, partly because we practice it in a world where very little worth gaining comes without a price. Although there has been public concern, some of it strident, about giving children “uppers,” psychostimulant medications help children who have ADHD. Are these medications “overprescribed”? I would bet they are. We tend, in this country, to overprescribe all types of drugs, certainly antibiotics with very substantial public health costs, and certainly other psychoactive agents such as diazepam. The argument obviously should not be whether we restrict methylphenidate further, but how to use it appropriately, as we should amoxicillin. When considering the use of a psychostimulant, we should be able to discuss with a family the issue of growth suppression, possibly from the underlying disorder affecting children who have ADHD and quite possibly as an effect of the medication. However, Dr. Joshi’s review of the literature strongly suggests that, particularly with proper dosing (and perhaps in some cases with “drug holidays”), the small risk of lost centimeters may be a price worth paying for many children to gain improved learning and social function.See Wender EH. Managing stimulant medication for attention-deficit/hyperactivity disorder. Pediatr Rev.2001;22:183–190." @default.
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• W4254910748 date "2002-02-01" @default.
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• W4254910748 title "ADHD, Growth Deficits, and Relationships to Psychostimulant Use" @default.
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• W4254910748 doi "https://doi.org/10.1542/pir.23.2.67" @default.
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