ADHD Drugs' Growth Impact Found to Be Insignificant

Stimulant medications for ADHD may alter short-term growth patterns in young patients, but while there's general agreement that final adult height is not seriously affected, longer-term studies are needed as stimulant formulations and prescribing practices change.

“This is an old issue,” said Harold Carlson, M.D., a professor of medicine and chief of the Division of Endocrinology and Metabolism at Stony Brook University in New York, in an interview. “It's been around for at least 30 years, and to some extent new studies are reinventing the wheel. But unfortunately, there is a dearth of long-term followup data. What's really needed is to follow these children to their final adult height.”

Two studies in the May Journal of the American Academy of Child and Adolescent Psychiatry reaffirmed that stimulant treatment of children with ADHD for up to three years had a negligible effect on adult height and weight. In one study, Steven Pliszka, M.D., of the Division of Child and Adolescent Psychiatry at the University of Texas Health Science Center at San Antonio, and three colleagues compared methylphenidate and mixed salts amphetamine and found no effect of stimulant type, drug holidays, or length of time in treatment on change in height Z score. Z scores are a way of analyzing the relationship of an individual measurement with the mean and standard deviation.

Pliszka and colleagues sought to see whether the two medications produced different effects on height and weight after at least one year of treatment. They recruited 66 patients on mixed salts amphetamine (MSA) and 113 on methylphenidate (MPH). No controls were used. Their mean age was 8.5 to 9.0 years, most were boys, and they had spent an average of about two and a half years in treatment. Height and weight standards from the National Center for Health Statistics were used.

Linear regression analysis showed a modest reduction in change in height, but that difference was caused largely by three outlier individuals at the end of the study. “Removal of three outliers rendered the relationship between adjusted cumulative stimulant dose and height change insignificant,” they wrote.

Children do not neatly follow weight and height percentile curves as they grow, the researchers added. They may shift percentiles as growth naturally speeds up or slows down, and as many children in the study moved to a higher percentile as moved to a lower one. All patients had drug holidays, so that could not be used as a variable.

Looking at a subset of 63 patients who took stimulants for three years, the researchers found no effect of stimulant type or time on height Z scores. The mean baseline weight in both medication groups was above the average for their age groups. Weight and body mass index declined after a year in treatment, but both showed a slight rebound toward baseline after that, although there was a slightly greater drop in weight for the MSA cohort. Neither weight nor body mass index (BMI) was affected by stimulant type.

“Individual patients will vary, however, in the response of their appetite to MSA or MPH,” wrote the researchers. They noted that a long-acting stimulant became available during the course of the study, and the effect of that development is not known.

“Most of the old studies used short-acting drugs given several times a day, so that drug concentrations went up and down in the course of the day,” said Carlson, arguing for longer-term research. “Long-acting drugs are now the mode, which raises concerns about continuous high levels of the drug.”

Also, he said, doctors used to prescribe stimulants for a few years and discontinue them at the end of adolescence. Now patients are more likely to be treated into adulthood, reflecting the view that ADHD is a lifelong disease.

“We don't know what taking these drugs for 20 years will do,” said Carlson.

The second study, of 178 children aged 6 to 13 years (mean=9.4 years) taking OROS methylphenidate (OROS MPH), an extended-release formulation, found that the children grew steadily in height over the 21 months of the trial, and the difference in expected height amounted to a decrease of only 0.23 cm. However, differences in height Z quartiles were not statistically significant. Furthermore, wrote Thomas Spencer, M.D., of Massachusetts General Hospital, and colleagues, “Any decrease in expected height is more likely to occur in taller children, which suggests that a decrease in expected growth is unlikely to lead to extremely short stature.”

Weight remained the same and BMI declined slightly at first, but both leveled off after four months, and children weighed an average of 1.23 kg less than expected by the end of the study. Growth standards were obtained from the Centers for Disease Control and Prevention Growth Chart guidelines.

“Drug holidays did not significantly affect growth,” according to the researchers. “For patients, the significance of a deficit in expected growth should be considered in the context of the benefits he or she receives from the medication and the magnitude of the deficit.”

As with any medication, outcome varies in the individual taking stimulants, said Carlson. “Some kids may be more sensitive to stimulants. Younger patients, those who are bigger or heavier before starting treatment, and boys may react more strongly.”

He said that more research is needed to determine the effect of stimulants in different age groups over longer times. In the meantime, pediatricians should monitor treated children carefully, checking their growth twice a year.“ If there are more than mild changes, then reconsider their treatment,” he said.

Spencer's study was supported by McNeil Consumer and Specialty Pharmaceuticals, and co-authors included two company employees. Pliszka serves on the speaker's bureau of Shire Pharmaceutical and McNeil Pharmaceuticals.

Abstracts of the two articles on stimulants and growth can be accessed at<www.jaacap.com> under the May issue. ▪