Disruptive Mood Dysregulation Disorder and Its Association with Treatment Trajectories and Outcomes in Youth with Attention-Deficit/Hyperactivity Disorder and Internalizing Disorders

OBJECTIVES: Disruptive mood dysregulation disorder (DMDD), along with other internalizing disorders, is associated with greater impairment in youth with attention-deficit/hyperactivity disorder (ADHD). However, it remains unclear whether DMDD is associated with differences in treatment course and outcomes among youth with ADHD and comorbid internalizing disorders. Using real-world data, this study compared treatment patterns and clinical outcomes among youth with ADHD and internalizing disorders with and without comorbid DMDD. METHODS: A retrospective cohort study analyzed electronic health records from the TriNetX U.S. Collaborative Network, including 340,225 youth aged 6-18 years with ADHD and at least one internalizing disorder (major depressive disorders or anxiety disorder), of whom 25,580 (7.5%) had comorbid DMDD. Outcomes included treatment patterns and clinical outcomes. Propensity score matching and Cox proportional hazards models adjusted for confounding were used to estimate relative risks (RR), adjusted hazard ratios (aHR), and 95% confidence intervals (CI) over 1 year. RESULTS: Youth with ADHD, internalizing disorders, and DMDD exhibited greater psychiatric comorbidity and higher healthcare utilization than those without DMDD. They received more ADHD medications, with a marked shift toward nonstimulants (RR 1.73, 95% CI 1.69-1.77), and other psychotropic medications, including antidepressants, antipsychotics, and mood stabilizers (RR range 1.36-3.02). New central nervous system (CNS) stimulant prescriptions did not differ between youth with and without DMDD. Compared with nonstimulants, CNS stimulants were associated with lower risks of all adverse outcomes-including suicidal ideation/attempts, inpatient hospitalization, emergency visits, and subsequent antipsychotic or mood stabilizer initiation-in youth both with and without DMDD (aHR range 0.33-0.73). CONCLUSIONS: Comorbid DMDD adds clinical complexity among youth with ADHD and internalizing disorders, influencing treatment patterns toward nonstimulants and other psychotropics. Despite this shift, CNS stimulants were associated with the most favorable outcomes across cohorts.