*Oppositional defiant disorder in children, *Youth with attention-deficit hyperactivity disorder, *Attention-deficit hyperactivity disorder, *Dyslexia, *Comorbidity, *Drugs, *Autism spectrum disorders, *Teenagers

More knowledge is needed about long-term ADHD medication and symptom, daily functioning, comorbidity, and tolerability outcomes. This "Long-term Medication for ADHD (LMA) trial" was a prospective observational 2-year trial in children and adolescents aged 6–18 years (extension of 1-year trial). Participants met criteria for DSM-5 ADHD (inattentive or combined), with complex comorbidities; autism spectrum disorder (31%), autistic traits (24%), oppositional symptoms (59%), anxiety (32%), dyslexia/language disorder (16%), borderline intellectual functioning (17%). Medication was individually tailored and followed-up at clinical visits (1, 2, 3, 6, 12, 18, 24 months). Primary outcome: Clinical Global Impression-Severity and Improvement scales (CGI-S, CGI-I). Secondary outcomes: Investigator-rated ADHD-Rating Scale, Weiss Functional Impairment Rating Scale-Parent report (WFIRS-P; Family, School Learning and Behavior, Life Skills, Self-Concept, Social Activities, and Risky Activities domains), comorbidity symptoms and adverse events (AEs). One hundred twenty-eight participants were enrolled (1-year trial only n = 27, LMA trial n = 101). Of these 29 (23%) discontinued, mainly due to AEs (n = 7), moving (n = 7), or no longer needing medication (n = 6). Main AEs were poor appetite, low mood, anxiety, irritability, fatigue. Improvements from baseline to 2 years were large in CGI-S (effect size (ES) 2.28), ADHD-RS (ES 2.06), and moderate to large in WFIRS-P (ES total 0.73, learning 0.4, family 0.67). Overall, the trial showed robust and sustained improvements in ADHD symptom severity and daily functioning over a period of 2 years of ADHD medication in children and adolescents with ADHD and complex comorbidities. Most AEs were mild. Comorbidity symptoms were improved after 1 year, particularly oppositional symptoms, depression, and anxiety. [ABSTRACT FROM AUTHOR]

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