An old antidepressant finds a new role treating the most common ADHD patient you see
STUDY: Adler LA et al, J Clin Psychiatry 2026;87(2)
STUDY TYPE: Open-label, uncontrolled trial
FUNDING: Supernus Pharmaceuticals
Background
Viloxazine began life as an antidepressant in Europe in 1974, but was repurposed in 2021 as Qelbree, FDA-approved for ADHD. But it shares a mechanism with antidepressants, blocking norepinephrine reuptake and modulating serotonin receptors. This open-label study builds on that pharmacology, testing it in ADHD with depression and anxiety.
The Study
- 161 adults with ADHD plus clinically significant depression and/or anxiety; 76% female, mean age 39.
- Viloxazine 200–600 mg/day for 14 weeks, added to existing medications including stimulants and antidepressants.
- Primary outcome: change in ADHD symptoms (AISRS scale). Secondary outcomes included depression (MADRS, PHQ-8) and anxiety (HAM-A, GAD-7).
Depression and anxiety scores improved, with response rates of 58 to 78% and remission rates ranged from 24% to 49%, depending on the measure used. ADHD scores fell as well, more than 70% of participants achieved at least a 30% reduction; 46% reached 50% or more.
Side Effects
Most adverse events were mild to moderate: Nausea (21%), insomnia (19%), constipation (14%), headache (11%), and fatigue (9%). About 15% discontinued due to adverse events. Five participants reported suicidal ideation; all resolved.
Limitations
No control group; open-label; 35% dropout rate. Whether the depression and anxiety improvements were a direct drug effect or a downstream benefit of better ADHD control is unknown.
Practice Implications
- Viloxazine already has 37 trials in depression. Most are controlled, but small and limited quality, with a dose range of 300–400 mg/day, so it makes sense for depression with ADHD.
- As for anxiety, I’ll wait for more proof. In the ADHD trials, it did not separate from placebo on anxiety (a secondary measure), and anxiety is a rare side effect. Atomoxetine does have controlled trials for ADHD with anxiety disorders.
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
