Real-world ADHD pharmacological treatment patterns and their association with negative clinical outcomes in youth with comorbid autism: a Swedish population-based study

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BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) medications can reduce ADHD symptom severity in individuals with comorbid autism spectrum disorder (ASD). However, clinical guidance on pharmacological treatment of ADHD in this clinical population remains limited and inconsistent. Characterising real-world treatment patterns (ie, initiation timing, medication choices, switching, discontinuation) and the impact of alternative medication choices on clinical outcomes is critical for informing evidence-based management strategies. OBJECTIVE: To (1) characterise ADHD pharmacological treatment patterns in youth with ADHD+ASD versus ADHD alone and (2) assess whether using alternative ADHD medications versus methylphenidate is associated with differential changes in negative clinical outcomes among youth with ADHD+ASD. METHODS: This is a population-based cohort study using Swedish national registers. The study included children (<13 years) and adolescents (13-17 years) with an incident ADHD diagnosis between 2007 and 2018 and followed-up until 2021, comparing youth with co-occurring ASD (n=24 117) and ADHD alone (n=79 830). Descriptive outcomes included time to pharmacological treatment initiation, medication type, number of medication switches and discontinuations. The primary outcome was changes in rates of inpatient psychiatric hospitalisations, accidental injuries and specialist care visits for substance use, depressive or anxiety disorders in the 1 year after versus the 1 year before medication initiation. FINDINGS: Individuals with ADHD+ASD experienced longer delays to treatment initiation (12-14% initiated >12 months after diagnosis vs 7-8% in ADHD alone). Children with ADHD+ASD were slightly more likely to discontinue treatment within 3 months (16% vs 12%) and had the highest average number of medication switches within 3 years (2.6; IQR 0.0-2.0). In within-individual analyses, comparisons of alternative ADHD medications versus methylphenidate did not yield statistically significant differences after correcting for multiple comparisons. CONCLUSIONS: Children with ADHD+ASD experienced longer delays to treatment initiation and more frequent medication switching compared with those with ADHD only. The effects of alternative ADHD medication options on key negative clinical outcomes appeared similar to those of methylphenidate. CLINICAL IMPLICATIONS: These findings suggest that, rather than recommending fixed first-line and second-line treatments for individuals with ADHD-ASD, clinical guidelines should emphasise appropriate training as well as prompt and individualised treatment based on a shared decision-making process.

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