Long-term methylphenidate use does not stunt growth in children with ADHD

Long-term treatment with methylphenidate does not increase risks of growth impairment and psychiatric or neurological adverse events (AEs) in children and adolescents with attention deficit hyperactivity disorder (ADHD), according to the international ADDUCE study co-led by the University of Hong Kong (HKU) and the University of Melbourne.

Methylphenidate is the most frequently prescribed medication for ADHD in many countries. In Hong Kong, approximately 2 percent of children and adolescents with ADHD received methylphenidate from the Hospital Authority in 2020. “Although methylphenidate’s short-term efficacy, tolerability and safety are supported by many randomized controlled trials [RCTs], long-term data are scarce, resulting in two rejections for inclusion in WHO’s Essential Medicines List [EML],” noted the researchers. [BMJ Evid Based Med 2023;28:75-77]

To investigate the long-term safety of methylphenidate, 1,410 participants aged 6–17 years (male, 76.3 percent; average age, 9.28 years) were recruited into three groups, including medication-naive ADHD patients who intended to start methylphenidate treatment (methylphenidate group), medication-naive ADHD patients who did not intend to start any ADHD medications (no methylphenidate group), and individuals without ADHD (controls). Height velocity was chosen as the primary outcome due to concerns that reduction in growth may be a common AE associated with long-term methylphenidate administration. [Lancet Psychiatry 2023;doi:10.1016/S2215-0366(23)00042-1]

After controlling for ADHD symptom severity and other variables, the research team found that 24-month treatment with methylphenidate was not associated with a reduction in growth (height velocity standard deviation [SD] score difference, -0.07; 95 percent confidence interval [CI], -0.18 to 0.04; p=0.20) or increased risks of psychiatric or neurological AEs (all p>0.05) vs the no methylphenidate group.

Long-term use of methylphenidate was associated with modest increases in systolic and diastolic blood pressure (differences, +0.04 mm Hg; 95 percent CI, 0.02–0.06; p<0.0001) and pulse rate (difference, +0.05 bpm; 95 percent CI, 0.02–0.08; p<0.0001) at month 24, but no serious AEs were reported.

“Our findings demonstrate the safety of methylphenidate treatment for 2 years in children and adolescents with ADHD. We also found no evidence to support that long-term methylphenidate treatment leads to a reduction in growth,” said Professor Ian Wong, Head of the Department of Pharmacology and Pharmacy, HKU.

Globally, access to ADHD medications remains challenging for millions of people as these medications are not listed on WHO’s EML. To evaluate multinational trends and patterns of ADHD medication consumption, the researchers conducted a longitudinal trend study using pharmaceutical sales data from IQVIA. [eClinicalMedicine 2022;doi:10.1016/j.eclinm.2022.101780]

Results showed that ADHD medication consumption in high-income countries (eg, the US and Canada) was 10- to 100-fold higher than in middle-income countries (eg, the Philippines and India). Notably, consumption rates of ADHD medication were considerably lower than the prevalence of ADHD in middle-income countries, indicating unmet treatment needs and inequity by country-income levels.

“ADDUCE strengthens the argument for the WHO to reconsider including methylphenidate in the EML,” commented Wong. “This will help address the observed inequity in ADHD medication consumption in middle-income countries [as] WHO’s EML guides medication procurement and availability in many middle-income countries."