Early treatment response as predictor of long-term outcome in a clinical cohort of children with ADHD.

This study investigates early onset of treatment response as predictor of symptomatic and functional outcome 3 years after initiation of methylphenidate (MPH) administration in a naturalistic, clinical cohort of children and adolescents with ADHD. Children were followed across an initial 12-week MPH treatment trial and after 3 years, with ratings of symptoms and impairment. Associations between a clinically significant MPH treatment response in week 3 (defined as ≥ 20% reduction in clinician-rated symptoms) and in week 12 (defined as ≥ 40% reduction), and 3-year outcome were tested in multivariate linear regression models, adjusting for sex, age, comorbidity, IQ, maternal education, parental psychiatric disorder, and baseline symptoms and function. We did not have information on treatment adherence or the nature of treatments beyond 12 weeks. 148 children, mean age 12.4 years (range 10-16 years), 77% males, participated in the follow-up. We found a significant decrease in symptom score from baseline [M = 41.9 (SD = 13.2)] to 3-year follow-up [M = 27.5 (SD = 12.7), p < 0.001, and in impairment score from baseline (M = 41.6 (SD = 19.4)] to 3-year follow-up [M = 35.6 (SD = 20.2), p = 0.005]. Treatment responses in week 3 and week 12 were significant predictors of the long-term outcome of symptoms, but not of impairment at 3-year follow-up, when adjusting for other well-known predictors. Early treatment response predicts long-term outcome over and above other well-known predictors. Clinicians should follow-up patients carefully, during the first months of treatment, and detect non-responders, since there might be a window of opportunity to alter the outcome, by changing the treatment strategy.Clinical trial registration: ClinicalTrials.gov, registration number NCT04366609, April 28, 2020 retrospectively registered.

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.

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.