Outcomes of a 12-week ecologically valid observational study of first treatment with methylphenidate in a representative clinical sample of drug naïve children with ADHD

Abstract

Randomized placebo-controlled trials have reported efficacy of methylphenidate (MPH) for Attention-deficit/hyperactivity disorder (ADHD); however, selection biases due to strict entry criteria may limit the generalizability of the findings. Few ecologically valid studies have investigated effectiveness of MPH in representative clinical populations of children. This independently funded study aims to describe treatment responses and their predictors during the first 12 weeks of MPH treatment using repeated measurements of symptoms and adverse reactions (ARs) to treatment in 207 children recently diagnosed with ADHD. The children were consecutively included from the Child and Adolescent Mental Health Centre, Mental Health Services, The Capital Region of Denmark. The children (mean age, 9.6 years [range 7–12], 75.4% males) were titrated with MPH, based on weekly assessments of symptoms (18-item ADHD-rating scale scores, ADHD-RS-C) and ARs. At study-end 187 (90.8%) children reached a mean end-dose of 1.0 mg/kg/day. A normalisation/borderline normalisation on ADHD-RS-C was achieved for 168 (81.2%) children on the Inattention and/or the Hyperactivity-Impulsivity subscale in week 12, and 31 (15.0%) children were nonresponders, which was defined as absence of normalisation/borderline normalisation (n = 19) or discontinuation due to ARs (n = 12), and eight (3.8%) children dropped out from follow-up. Nonresponders were characterised by more severe symptoms of Hyperactivity-Impulsivity and global impairment before the treatment. ARs were few; the most prominent were appetite reduction and weight loss. A decrease in AR-like symptoms during the treatment period questions the validity of currently available standard instruments designed to measure ARs of MPH. This ecologically valid observational study supports prior randomized placebo-controlled trials; 81.2% of the children responded favourably in multiple domains with few harmful effects to carefully titrated MPH. Clinical trial registration: ClinicalTrials.gov with registration number NCT04366609.

Predicting the Response of Children and Adolescents With ADHD to Methylphenidate: A Systematic Review

“…Ghuman et al (2007) and Newcorn et al (2010) reported that associated comorbidities to ADHD have been shown to alter response to MPH, in samples of preschoolers and adolescents respectively. Conversely, in samples of school-age children, Chan et al (2017) and Kaalund-Brok et al (2021) found no relation between comorbid disorders and MPH response.…”

“…van der Oord et al ( 2008) described a better response to MPH in children with higher IQ based on teachers' reports but not parental reports. In a population of ADHD children with no comorbid intellectual deficiency, Kaalund-Brok et al (2021) found IQ above 85 versus IQ below or equal to 85 but above 70 being associated with a better chance of normalization or borderline normalization of the inattention and hyperactivity-impulsivity symptomatology, whereas the weekly reduction of inattention and of hyperactivityimpulsivity showed no differences between IQ groups. In similar populations of children (IQ > 70), eight studies show no association between IQ and response to MPH (Chan et al, 2017;Chazan et al, 2011;Grizenko et al, 2006;Johnston et al, 2015;Kim et al, 2015;Lee et al, 2009;Ter-Stepanian et al, 2010), including in preschoolers (Ghuman et al, 2007).…”

“…Most studies included in our review specify that age does not moderate MPH response ( n = 14) (Aman et al, 2003; Chazan et al, 2011; Ghuman et al, 2007; Johnston et al, 2015; Kaalund-Brok et al, 2021; Kim et al, 2015; Lee et al, 2009; Masi et al, 2020; Newcorn et al, 2010; Park et al, 2013; Sangal & Sangal, 2004; Say et al, 2015; Smith et al, 1998; Ter-Stepanian et al, 2010), even in preschoolers (Ghuman et al, 2007). Smith et al (1998) compared the therapeutic effect of MPH on ADHD during childhood versus adolescence and concluded that MPH is equally effective in children and adolescents.…”

“…In the MTA study, children with the most severe levels of ADHD showed less chance of response than children with less severe ADHD at 14 months (MTA Cooperative Group, 1999), but initial symptom severity did not moderate children's 36-month treatment responses (Jensen et al, 2007). Kaalund-Brok et al (2021) found nonresponders having more severe symptoms of hyperactivity-impulsivity and global impairment than responders at baseline. Six studies describe the opposite pattern, severity of symptoms being predictive of a better response (Coghill et al, 2007;Denney & Rapport, 1999;Newcorn et al, 2010;Park et al, 2013;Thomson & Varley, 1998;Zeiner et al, 1999).…”

Desvelando os efeitos adversos do metilfenidato na atenção infanto-juvenil

“…A redução do apetite é um efeito colateral associado ao uso do Metilfenidato 4,5,21,22,24-27 e está diretamente relacionada com a perda de peso, incômodos estomacais e algia abdominal 4,21,22,24,27,28 . Outros sintomas como náuseas, emagrecimento, boca seca, gosto amargo na boca, sensação de intensificação do metabolismo corporal, sensação de fraqueza e cansaço estão associados com perda do apetite e do desenvolvimento da estatura 4,21,22,24 .…”