Recently, the use of methylphenidate has been increasing considerably for the treatment of attention deficit hyperactivity disorder (ADHD) in many countries.¹ However, the risk-to-benefit ratio of the drug remains uncertain for long-term use due to the lack of long-term safety and tolerability data.¹ In the ADDUCE trial, researchers from LKS Faculty of Medicine, the University of Hong Kong (HKUMed) and University of Melbourne found that treatment of ADHD children with methylphenidate for 2 years is safe without reduction in growth.¹ 

ADHD is a neurodevelopmental disorder with a global prevalence of 5%-7% in children and adolescents and is more common in males than females.¹ Methylphenidate, a norepinephrine and dopamine reuptake inhibitor (NDRI), is the first-line treatment option for ADHD.¹ By improving the dopaminergic and noradrenergic modulation of cortical and subcortical circuits, it is believed that methylphenidate is able to increase the efficiency of prefrontal cortex activity, optimizing the executive and attentional functions among ADHD patients.¹ Although the drug has been extensively utilized for the treatment of ADHD in clinical practice, safety, and tolerability data are primarily short-term and medium-term.¹ Hence, there is a lack of long-term data of at least 52 weeks regarding the safety and tolerability of methylphenidate.¹  

The ADDUCE study by HKUMed was a 2-year naturalistic, prospective, pharmacovigilance, multicenter study designed to evaluate the long-term safety of methylphenidate in ADHD children and adolescents aged 6-17 years.¹ From February 1, 2012, to January 31, 2016, a total of 756 patients were included in the methylphenidate group, 391 in the no-methylphenidate group, and 263 in the control group.¹ The primary outcome was height velocity (i.e., the height velocity standard deviation score), while the secondary outcomes were weight and body mass index (BMI).¹ Other outcomes included cardiovascular health assessed by the pulse rate and blood pressure; and the psychiatric outcomes evaluated through the Mood and Feelings Questionnaire, etc.¹ 

Results showed that no serious adverse events (SAEs) were reported and no significant difference in height velocity between the methylphenidate, as well as no-methylphenidate groups throughout the study.¹ Despite the initial slowing at 6 months for weight velocity in the methylphenidate group, no significant difference was seen at 12 and 24 months.¹ An increase in systolic blood pressure (SBP) from baseline to 24 months was seen in the methylphenidate group (from 108mmHg to 113mmHg; p<0.0001) and in the no-methylphenidate group (from 104mmHg to 108mmHg; p<0.0001), but not in the control group.¹ Increases in diastolic blood pressure (DBP) (from 65mmHg to 67mmHg; p=0.02) and pulse rate (from 80 beats to 83 beats per minute) were also observed in the methylphenidate group, but not in the other 2 groups.¹ Improvements in self-rated and parent-rated mood were greater in the methylphenidate group than in the no-methylphenidate group after 24 months (p=0.01 and p=0.02, respectively).¹ The scores on the Abnormal Involuntary Movement Scale (AIMS), which indicates abnormal movements, decreased more in the methylphenidate group than in the no-methylphenidate group at 6 months (p<0.0001) and 12 months (p<0.0016), but not at 24 months (p=0.09).¹  

In summary, the use of methylphenidate for treating ADHD has been increasing in recent years, amplifying the calls for more understanding of its long-term safety profile.¹ The ADDUCE study demonstrated the acceptable long-term safety of methylphenidate without reduction in growth, supporting its usage in children and adolescents with ADHD.¹