Clinical Summary: 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
Adults with ADHD commonly present with depression and anxiety symptoms, yet these patients are routinely excluded from ADHD trials, leaving clinicians to treat a high-burden population with limited evidence. This study addresses whether viloxazine ER can improve ADHD symptoms in adults who also have prominent mood and/or anxiety symptoms while being used alone or alongside other psychiatric medications.
Key Findings
- At week 14/EOS, mean (SD) change from baseline in AISRS total score was −17.3 (11.34) (P < .0001), representing a reduction from baseline of −45.3% (27.31%); 71.8% and 45.6% of participants achieved ≥30% and ≥50% reduction in AISRS total score, respectively.
- Depression and anxiety symptoms also improved by week 14/EOS: mean (SD) change from baseline was −15.5 (7.12) for MADRS total score and −14.2 (5.79) for HAM-A total score, with ≥50% reduction achieved by 57.5% on MADRS and 70.8% on HAM-A; symptom remission was achieved by 28.3% and 24.2%, respectively.
- Patient-reported outcomes mirrored clinician-rated improvement: at week 14/EOS, mean (SD) change from baseline was −28.4 (14.89) for ASRSv1.1-SC total score (P < .0001) and −10.6 (5.24) for PHQ-8 total score, while 78.4% achieved ≥50% reduction on PHQ-8 and 48.6% reached remission.
- Functional outcomes improved at week 14/EOS, including mean (SD) change from baseline in WPAI:SHP percentages of −23.08 (26.072; P < .0001) for presenteeism, −36.06 (24.230; P < .0001) for regular activity, and −22.32 (26.915; P < .0001) for work productivity.
- Viloxazine ER was generally well tolerated, but adverse-effect monitoring is essential: TEAEs occurred in 70.8% of participants, 14.9% discontinued due to TEAEs, 3.7% experienced serious TEAEs, 3.1% reported TEAEs of suicidal ideation, and at week 14/EOS 20.0% had a >15 mm Hg increase in SBP, 13.3% had a >15 mm Hg increase in DBP, and 10.2% had a >20 beats per minute increase in pulse rate.
In adults with ADHD plus prominent depression and/or anxiety symptoms, viloxazine ER was associated with substantial improvement across ADHD, mood, anxiety, and work-function measures over 14 weeks, including in patients taking concomitant psychiatric medications. Use it as a reasonable nonstimulant option in this comorbid population, with careful monitoring for early adverse effects, suicidality, and vital sign changes.
Practice Implications
- Consider viloxazine ER when treating adults with ADHD who also have clinically significant depression and/or anxiety symptoms, especially when a nonstimulant option is preferred.
- Do not assume comorbid mood or anxiety symptoms preclude benefit on core ADHD symptoms; by week 14/EOS, 71.8% achieved ≥30% AISRS reduction and 45.6% achieved ≥50% reduction.
- If viloxazine ER is added to existing psychiatric treatment, monitor tolerability closely, since 28.6% took stimulants, 44.7% took antidepressants, and 14.9% took anxiolytic and/or hypnotic medications during the study.
- Build early follow-up around safety checks for insomnia, nausea, appetite loss, suicidal ideation, blood pressure, and pulse rate, given that 14.9% discontinued for TEAEs, 3.1% reported TEAEs of suicidal ideation, and 20.0%, 13.3%, and 10.2% had notable increases in SBP, DBP, and pulse rate, respectively.
