TY - JOUR

T1 - 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

AU - Kaalund-Brok, Kristine

AU - Houmann, Tine Bodil

AU - Hebsgaard, Marie Bang

AU - Lauritsen, Maj Britt Glenn

AU - Lundstrøm, Louise Hyldborg

AU - Grønning, Helene

AU - Darling, Lise

AU - Reinert-Petersen, Susanna

AU - Petersen, Morten Aagaard

AU - Jepsen, Jens Richardt Møllegaard

AU - Pagsberg, Anne Katrine

AU - Plessen, Kerstin Jessica

AU - Rasmussen, Henrik Berg

AU - Jeppesen, Pia

N1 - Publisher Copyright: © 2021 Kaalund-Brok et al.

PY - 2021/10

Y1 - 2021/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85117755866&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0253727

DO - 10.1371/journal.pone.0253727

M3 - Journal article

C2 - 34673771

AN - SCOPUS:85117755866

VL - 16

SP - 1

EP - 29

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 10

M1 - e0253727

ER -