Acute Tolerability of Methylphenidate in Treatment-Naïve Children with ADHD: An Analysis of Naturalistically Collected Data from Clinical Practice

• Published in: Paediatric drugs Vol. 24; no. 2; pp. 147 - 154
• Main Authors: Masi, Gabriele, Pfanner, Chiara, Liboni, Francesca, Lenzi, Francesca, Villafranca, Arianna, D’Acunto, Giulia, Fantozzi, Pamela, Falcone, Francesca, Simonelli, Valerio, Muratori, Pietro, Levantini, Valentina, Favole, Irene, Amianto, Federico, Davico, Chiara, Vitiello, Benedetto
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-03-2022; Springer; Springer Nature B.V
• Subjects: Adolescent; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention deficit hyperactivity disorder; Blood pressure; Central Nervous System Stimulants - adverse effects; Child; Children & youth; Clinical medicine; Delayed-Action Preparations; Dosage and administration; Drug dosages; Drug therapy; Estimates; Evaluation; Female; Headaches; Heart rate; Humans; Intellectual disabilities; Internal Medicine; Male; Medicine; Medicine & Public Health; Methylphenidate; Methylphenidate - adverse effects; Methylphenidate hydrochloride; Original; Original Research Article; Patient compliance; Pediatrics; Pharmacotherapy; Regulatory agencies; Retrospective Studies; Sleep; Treatment Outcome; Italy
• ISSN: 1174-5878; 1179-2019
• DOI: 10.1007/s40272-022-00492-4

Objectives
The acute tolerability of methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD) has been studied mainly in research samples. Taking advantage of the mandatory test-dose procedure required for starting MPH in Italy, this study aimed to assess the incidence of intolerable adverse events after initial exposure to MPH in routine clinical practice.
Methods
The medical records of 480 consecutively treated, previously drug-naïve children and adolescents with ADHD (90% male, mean age 10.6 ± 3.0 years) were retrospectively analyzed. All children received an initial single dose of MPH immediate release (5 or 10 mg) followed by a 4-hour direct medical observation. Heart rate and blood pressure were measured at dosing and 1, 2, and 3 hours afterwards. If the first dose was well tolerated, the child continued treatment with MPH 5–20 mg daily, and was reassessed a week later.
Results
Eleven patients (2.3%, 95% CI 1.1–4.1) interrupted treatment within a week of initiation because of the following adverse events: irritability (
n
 = 3), tics worsening (
n
 = 3), reduced appetite (
n
 = 1), enuresis (
n
 = 1), hallucinations (
n
 = 1), hyperfocus (
n
 = 1), and ‘rebound’ behavioral worsening (
n
 = 1). The most common adverse events were reduced appetite (20%), irritability (14.2%), headache (10.6%), sleep problems (9.4%), stomachache (9.4%), and tics (5%). Intellectual disability increased the risk of any adverse event in general and of irritability in particular. No cardiovascular symptom was clinically reported. However, routine assessments of vital signs during the first 3 hours after the first dose of MPH showed that 9% of the children had a 20% increase in heart rate, 8.8% had a 20% increase in diastolic blood pressure and 4.5% had a 20% increase in systolic blood pressure. Of these, 25.2% still had an elevated heart rate 1 week later.
Conclusions
Among stimulant-naïve children in clinical practice, the incidence of acute MPH intolerance can be estimated to be between 1.2 and 4.1%. An asymptomatic elevation in cardiovascular parameters can be observed in about 1 out of 10 children and warrants monitoring during ongoing treatment.