Individualizing the dosage of Methylphenidate in children with attention deficit hyperactivity disorder

Hoda Shirafkan,Javad Mahmoudi-Gharaei,Mehdi Yaseri,Seyyed Ali Mozaffarpur,Mostafa Hoseini,Akbar Fotouhi

doi:10.1186/s12874-020-00934-y

Abstract

BackgroundAttention deficit hyperactivity disorder (ADHD) is one of the most common childhood mental health disorders. Stimulant drugs as the most commonly used treatment and first-line therapy for ADHD have side effects. One of the newest approaches to select the best choices and optimize dosages of medications is personalized medicine.MethodsThis historical cohort study was carried out on the data taken from the period of 2008 to 2015. Eligible subjects were included in the study randomly. We used mixed-effects logistic regression models to personalize the dosage of Methylphenidate (MPH) in ADHD. The patients’ heterogeneity was considered using subject-specific random effects, which are treated as the realizations of a stochastic process. To recommend a personalized dosage for a new patient, a two-step procedure was proposed. In the first step, we obtained estimates for population parameters. In the second step, the dosage of the drug for a new patient was updated at each follow-up.ResultsOf the 221 children enrolled in the study, 169 (76.5%) were male and 52 (23.5%) were females. The overall mean age at the beginning of the study is 82.5 (± 26.5) months. In multivariable mixed logit model, three variables (severity of ADHD, time duration receiving MPH, and dosage of MPH) had a significant relationship with improvement. Based on this model the personalized dosage of MPH was obtained.ConclusionsTo determine the dosage of MPH for a new patient, the more the severity of baseline is, the more of an initial dose is required. To recommend the dose in the next times, first, the estimation of random coefficient should be updated. The optimum dose increased when the severity of ADHD increased. Also, the results show that the optimum dose of MPH as one proceeds through the period of treatment will decreased.

Highlights

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood mental health disorders
This study evaluates the relationship between dosage of methylphenidate (MPH) and other important factors with response in ADHD patients under the framework of a mixed-effect logit model; proposes an optimal dose on the basis of the individualized factors of each patient
Evaluating 298 records, the sample size of 221 was achieved that means 77 records didn’t meet the eligibility criteria. This 77 records were excluded because Conners’ Parent Rating Scale-revised Short Form (CPRS-R):S was not correctly completed in 22 records, the main complaint was not ADHD in 19 records, other drugs were prescribed instead of MPH for 16 records, 14 records did not have any follow up, and for 6 records the age was less than 3 years old

Summary

Introduction

Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood mental health disorders. The etiology of ADHD is multi-factorial [4]. It is a combination of genetic [5, 6] and environmental (e.g., exposure to alcohol or lead, prenatal maternal smoking, prematurity, pregnancy complications, and low birth weight) [7, 8] factors. ADHD symptoms (hyperactivity, impulsiveness, and a developmental lack of attention) could cause significant damage in school tasks [9] and in the functions of daily activities [10]. In most children with ADHD, symptoms continue into adolescence and adulthood; it leads to social, occupational and personal dysfunctions [11]; early diagnosis and Shirafkan et al BMC Medical Research Methodology (2020) 20:56 appropriate treatment could be beneficial [12]. ADHD often accompany other mental and behavioral disorders [9]

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