Delayed-Release ADHD Therapy Slightly Mitigates Slowed Growth in Kids

NASHVILLE — Youth with attention-deficit/hyperactivity disorder (ADHD) saw mildly different growth trajectories with certain popular medications, researchers reported.

Compared with youth prescribed lisdexamfetamine dimesylate (LDX; Vyvanse), those who took delayed release/extended-release methylphenidate (DR/ER-MPH; Jornay PM) saw a greater weight trajectory in the first year after starting treatment (estimated post-index slope 2.65 for LDX vs 7.22, difference P

One year after starting these medications, the model-adjusted average weight for youth on LDX was about 43 kg (vs 43.4 kg at index) compared with about 47 kg (vs 40.1 kg at index) for kids on DR/ER-MPH. A year prior to starting any medication, both groups of children had average weights of around 37 kg, according to the poster from Weddige and colleagues at Psych Congress 2023.

“We’re showing here that the weight was continuing on that growth velocity [with DR/ER-MPH], whereas there was a slight leveling off with Vyvanse,” Weddige explained to MedPage Today.

While the two medications groups didn’t see a significant difference when it came to height trajectories, kids on DR/ER-MPH did see numerically higher average heights 1 year after starting treatment (estimated post-index slope 4.00 for LDX vs 5.72 for DR/ER-MPH, P=0.2301). At this 1-year mark, average heights were around 146 cm and 148 cm for youth on LDX and DR/ER-MPH, respectively. At the time of starting the medication, average heights were 141.1 cm for those on LDX and 140.3 cm for those on DR/ER-MPH.

Weddige’s group also compared growth trajectories of kids on DR/ER-MPH with those prescribed osmotic release oral system methylphenidate (OROS MPH; Concerta). In this comparison, kids on DR/ER-MPH likewise saw numerically higher height (5.12 vs 5.74 slope) and weight (5.28 vs 6.06 slope) trajectories within the year after starting medication, though neither of these differences were statistically significant.

“DR/ER-MPH is an evening dosed, delayed-release, and extended-release methylphenidate that’s absorbed in the colon,” Weddige explained during a poster presentation. “It has no immediate release component and provides a dose-dependent duration of effect for individuals with ADHD.”

“So as a result of having no [immediate release] component and a more gradual colonic absorption, its PK [pharmacokinetics] profile is monophasic with a gradual ascending curve and an extended elimination phase,” he continued. “A smooth PK profile with fewer peaks and troughs and methylphenidate plasma concentration is hypothesized to be associated with less appetite suppression throughout the day.”

Typical stimulants used to manage ADHD are often associated with a slowed growth rate in pediatric patients, he explained.

The real-world pilot study used a retrospective observational database of youth, ages 6-17 years, diagnosed with ADHD. Using ambulatory electronic health record databases, Weddige’s group pulled records of those newly prescribed one of these three ADHD agents between July 2019 to June 2020. The index date was defined as the first prescription claim date.

“An index date means this is the first prescription claim, and from the database that we saw that they were prescribed one of the three agents,” Weddige explained. “So we wanted to a 1-year look back, and we also wanted to do a 1-year look forward.”

The final sample included 83 patients on DR/ER-MPH, 240 on OROS MPH, and 403 on LDX. Youth on OROS MPH tended to be slightly older (average age 11.6) and there was a higher prevalence of white patients (59.6%). Compared with the other two medications, LDX had the highest prevalence of female patients.

“The reason for the low numbers of Jornay PM is because we need to keep in mind this was done during the first year of it’s availability,” noted Weddige.

When first starting their medication, the average daily dose was 35 mg for DR/ER-MPH, 24.8 mg for LDX, and 37.2 mg for OROS MPH. One year later, the average daily doses were 53.4 mg, 31.8 mg, and 39.0 mg, respectively. The number of persistent days was the same across all three medications (358 days).

Weddige noted that an important limitation of the analysis was the small sample size of patients on DR/ER-MPH, which may have led to greater variability in those patients’ growth trajectory models. The researchers also pointed out that because the study period overlapped with the start of the COVID-19 pandemic, it’s possible that normal growth patterns may have been impacted in youth.