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.