Effect of pharmacological treatment of attention-deficit/hyperactivity disorder on later psychiatric comorbidity: a population-based prospective long-term study.

BACKGROUND Psychiatric comorbidity is frequent among persons with attention-deficit/hyperactivity disorder (ADHD). Whether pharmacological treatment of ADHD influences the incidence of psychiatric comorbidity is uncertain. OBJECTIVE To investigate associations and causal relations between pharmacological treatment of ADHD and incidence of subsequent comorbid psychiatric diagnoses. METHODS We employed registry data covering all individuals aged 5-18 years in Norway who were diagnosed with ADHD during 2009-2011 (n=8051), followed until 2020. We used linear probability models (LPM) and instrumental variable (IV) analyses to examine associations and causal effects, respectively, between pharmacological treatment and subsequent comorbidity. FINDINGS From time of ADHD diagnosis to 9 years of follow-up, 63% of patients were registered with comorbid psychiatric disorders. For males, LPM showed associations between ADHD medication and several incident comorbidities, but strength and direction of associations and consistency over time varied. For females, no associations were statistically significant. IV analyses for selected categories isolating effects among patients 'on the margin of treatment' showed a protective effect for a category of stress-related disorders in females and for tic disorders in males for the first 2 and 3 years of pharmacological treatment, respectively. CONCLUSIONS Overall, LPM and IV analyses did not provide consistent or credible support for long-term effects of pharmacological treatment on later psychiatric comorbidity. However, IV results suggest that for patients on the margin of treatment, pharmacological treatment may initially reduce the incidence of certain categories of comorbid disorders. CLINICAL IMPLICATIONS Clinicians working with persons with ADHD should monitor the effects of ADHD medication on later psychiatric comorbidity. TRIAL REGISTRATION NUMBER ISRCTN11891971.