Viloxazine is a more effective treatment option for children and adults with combined-type attention deficit hyperactivity disorder (ADHD) compared with atomoxetine and is linked to fewer side effects, according to new research published in CNS Drugs.
Viloxazine was approved by the US Food and Drug Administration (FDA) for the treatment of ADHD in 2021. The agent was classified as a norepinephrine (NE) reuptake inhibitor and “equated with atomoxetine in terms of its mechanism of action and corresponding mild efficacy in ADHD,” the study authors noted. “However, additional serotonin receptor targets have been more recently identified that may better explain its primary mechanism of action beyond the NE reuptake inhibition that distinguishes it from atomoxetine pharmacologically.”
To compare the 2 agents, a total of 50 patients, 35 of whom were children, participated in an open-label, single-arm retrospective analysis. Participants received a mean dose of atomoxetine 60 mg (25–100 mg/d) over a 4-week trial period. They then had a 5-day washout period before voluntarily opting to receive a mean dose of viloxazine extended-release (VER) 300 mg (100–600 mg/d) for another 4-week trial period. Both of these medications were titrated according to US Food and Drug Administration guidelines, and participants were permitted to continue to use concomitant psychostimulant medication throughout the study.
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Before starting each medication, participants completed either the pediatric ADHD-Rating Scale-5 (ADHD-RS-5) or the Adult Investigator Symptom Rating Scale (AISRS). These tests were repeated 4 weeks after treatment with each medication, or upon earlier response or discontinuation due to side effects.
Nearly all of the participants (96%) stated that they preferred taking VER vs atomoxetine. At 2 weeks of treatment on each medication, 14% of patients taking atomoxetine reported a positive response compared with 86% of patients taking VER.
In children, VER significantly improved ADHD-RS5 mean scores from (40.3 ± 10.3) at baseline to (13.9 ± 10.2) after treatment with VER (Table). Similarly, adults had higher mean AISRS scores after treatment with VER (37.3 ± 11.8 at baseline vs 11.9 ± 9.4 after taking VER). Both children and adults demonstrated greater improvement in inattention (P < 0.004), and hyperactivity/impulsivity (P < 0.002) when taking VER vs atomoxetine.
Table. Change in ADHD Rating Scales From Baseline to 4-Weeks After Treatment
| Scale | Baseline | Viloxazine | Atomoxetine |
| ADHD-RS-5 | 40.3 ± 10.3 | 13.9 ± 10.2 | 33.1 ± 12.1 |
| AISRS | 37.3 ± 11.8 | 11.9 ± 9.4 | 28.8 ± 14.9 |
Participants reported faster symptom improvement when taking VER compared with atomoxetine at 2 weeks, 87% of adults taking VER reported a positive response compared with 13% of adults taking atomoxetine. In children, 89% of participants reported symptom improvement at 2 weeks while taking VER compared with 14% of child participants who reported symptom improvement at 2 weeks while taking atomoxetine.
Approximately a third of patients (36%) discontinued atomoxetine due to side effects: 6 patients reported gastrointestinal upset, 6 reported irritability, 5 reported fatigue, and 1 reported insomnia. Most patients did not discontinue VER due to side effects (96%), though 4% discontinued VER use due to fatigue.
Of the 26 participants who completed the 4-week VER treatment period and were taking psychostimulants, 22 (85%) decided to taper their psychostimulants after they were stabilized on VER. In this group of 22, all of the children (n=15), as well as 7 of the 11 adults (64%), chose to taper their psychostimulants.
“While psychostimulants have demonstrated superiority to nonstimulants in rapidly improving inattention, risk for abuse and side effects, such as insomnia, appetite suppression, wear off, and potential exacerbation of mood, anxiety, and tics, give clinicians cause to consider prescribing nonstimulants either as monotherapy
or in combination with psychostimulants to enhance efficacy and/or mitigate side effects of psychostimulants,” wrote the authors.
The researchers recommend that clinicians consider VER as a first-line nonstimulant option for pediatric and adult ADHD patients either in combination with psychostimulants or as a standalone therapy for patients for whom psychostimulants are not suitable.
While this study was limited by having a small, heterogeneous sample of patients and did not have a control group, the results indicate that viloxazine is significantly more effective in improving inattention, hyperactivity, and impulsivity.
The authors of the study have no conflicts of interest to disclose.
References
Price MZ, Price RL. Extended-release viloxazine compared with atomoxetine for attention deficit hyperactivity disorder. CNS Drugs. 2023;37(7):655-660. doi:10.1007/s40263-023-01023-6
