Viloxazine Extended Release in Adults With Attention-Deficit/Hyperactivity Disorder and Depression and/or Anxiety Symptoms: Results From a Decentralized, Open-Label, Phase 4 Trial.

Objective: Adult attention-deficit/hyperactivity disorder (ADHD) is commonly associated with comorbidities, including depression and anxiety; however, most ADHD treatment studies exclude people with these conditions. This phase 4, open-label, decentralized clinical trial (conducted March 25, 2024-December 11, 2024) evaluated viloxazine ER (extended-release capsules, an FDA-approved nonstimulant medication for ADHD) in adults with ADHD (based on DSM-5-TR) and comorbid depression and/or anxiety symptoms. Methods: Participants received viloxazine ER (200-600 mg/d) for 14 weeks added to existing medications (including stimulant, antidepressant, or anxiolytic medications). Efficacy and safety measures (assessed via televisit, mobile phone app, and home monitoring devices) included clinician-and patient-reported scales evaluating ADHD, depression, and anxiety symptoms, treatment-emergent adverse events, blood pressure, pulse rate, weight, and suicidality assessment. The primary end point was change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) total score. Results: Among participants receiving viloxazine ER (n=161; mean age, 39.4 years; female, 75.8%), almost all (99.4%) had substantial depression and anxiety symptoms. AISRS total score was significantly reduced (improved) from baseline (mean [SD], 37.5 [6.53]; n=150) at week 14/end of study (EOS) (mean [SD] change, -17.3 [11.34]; P<.0001); similar results were observed for patient-reported ADHD symptoms. Depression and anxiety rating scales were significantly improved from baseline to week 14/EOS (all P<.0001). Safety outcomes were consistent with previous viloxazine ER studies; 24 participants (14.9%) had adverse events leading to study discontinuation. Conclusions: Viloxazine ER was well tolerated and associated with improvements in ADHD, depression, and anxiety symptoms in this real-world study of adults with ADHD and comorbid symptoms. Trial Registration: ClinicalTrials.gov identifier: NCT06185985.