Adherence and Acceptability: How Viloxazine ER Stacks Up Against Other ADHD Medications

This article examines how viloxazine ER may improve adherence to ADHD treatment compared to other medications. As a non-stimulant with once-daily dosing, rapid onset, and low risk of misuse or cardiovascular issues, viloxazine ER addresses common barriers to adherence. Studies show higher patient preference and fewer side effects versus atomoxetine, making it a promising option for long-term treatment success. 

Nonadherence With ADHD Medications: Defining the Problem 

Despite the safety and effectiveness of ADHD medications, nonadherence—particularly to stimulants—is common, with up to 50% of patients discontinuing treatment.¹ Poor adherence is linked to reduced ADHD symptom control and may compromise long-term outcomes, contributing to negative events such as poor school performance, motor vehicle accidents, injuries, substance abuse, and even criminality.^1-4 

Adherence tends to decline during adolescence, partly due to teens’ less favorable attitudes toward medications compared to their parents.¹ Medication dosing regimens that require multiple daily doses can also negatively affect adherence; hence, once-daily regimens are generally preferred.³ Additional factors contributing to nonadherence include stigma, adverse reactions, parental reluctance, and a perceived lack of efficacy.¹ Adverse effects, such as appetite suppression, insomnia, and mood changes, can result in drug holidays to mitigate those effects.⁵ Furthermore, rebound symptoms can occur when a short-acting (or even a long-acting) stimulant drug wears off, which can discourage proper use.³  

Adherence to stimulants—the established first-line therapy for ADHD—is additionally hindered by their abuse potential and the need to navigate tight regulations for refills due to their Schedule II status.^3,6,7 Additionally, parents may be reluctant to have their children use stimulants at all due to their potential for misuse, meaning that acceptance of these medications, let alone adherence once prescribed, may be an issue.¹  

Additional factors contributing to nonadherence with non-stimulants include delayed onset of effect (leading to a perceived lack of efficacy), monitoring requirements secondary to potential cardiovascular effects, and adverse events such as daytime sedation, fatigue, dizziness, gastrointestinal upset, and irritability. Non-stimulants may either raise blood pressure and pulse rates (atomoxetine, viloxazine) or decrease them (guanfacine, clonidine).^7,8 Stimulants and clonidine carry warnings about the potential for serious cardiovascular disease.^9-11 

Viloxazine: Potential Effects on Adherence 

The newest entrant to the ADHD armamentarium, viloxazine extended-release (ER), is a non-stimulant treatment option for ADHD in children, adolescents, and adults.¹² Like other non-stimulant medications, viloxazine ER is not a controlled substance, offering a potential adherence advantage in certain patient populations.⁶ As such, it is less likely to be diverted to another person or misused off schedule to, for example, maintain alertness during study, achieve a “high,” or enhance effects of other recreational-use drugs. By avoiding the regulatory hurdles, refill complications, and stigma associated with Schedule II stimulants—key drivers of nonadherence^3,6,7—viloxazine ER may be more acceptable to both patients and caregivers, potentially enhancing adherence. 

Like other non-stimulants, viloxazine ER offers once-daily dosing for around-the-clock efficacy and avoids the end-of-dose rebound effects that can undermine adherence.^3,7 However, viloxazine appears to have a more rapid onset of efficacy (1 to 2 weeks) than observed with another SNRI, atomoxetine (4 weeks).^7,13 Also, unlike atomoxetine, guanfacine, and clonidine,³ viloxazine has not been associated with significant cardiovascular risk that might discourage use⁷; hence, tolerability concerns that exist with stimulants and other non-stimulants may be less likely to diminish treatment adherence with viloxazine ER.  

This combination of once-daily dosing, rapid onset of effect, and favorable tolerability profile may reduce multiple barriers to adherence, including perceived lack of efficacy and adverse effects.^1,3,14 The absence of significant cardiovascular risks commonly seen with other non-stimulants may further improve willingness to initiate and continue therapy.⁷ 

Direct comparisons of viloxazine ER with guanfacine or clonidine are lacking, but a within-subject crossover study compared viloxazine ER with atomoxetine in 35 pediatric patients and 15 adults with ADHD.¹⁴ Thirty-six percent of participants discontinued atomoxetine due to adverse events, including gastrointestinal symptoms (n=6), irritability (n=6), fatigue (n=5), and insomnia (n=1).¹⁴ In contrast, only 2 participants discontinued viloxazine, both citing fatigue.¹⁴ Nearly all participants (96%) preferred viloxazine ER over atomoxetine. Moreover, among participants who were stabilized on viloxazine, 22 of 26 (85%) chose to reduce their use of psychostimulants, including all 15 children (100%) and 7 of 11 adults (64%).¹⁴   

Fewer discontinuations due to adverse events and high patient preference suggest viloxazine ER may be more acceptable to patients, which would support long-term adherence.^1,14 The observed reduction in psychostimulant use¹⁴ also points to viloxazine’s role in minimizing exposure to drugs with high misuse potential, a known barrier to sustained adherence. 

Conclusion 

Nonadherence to ADHD medications, especially stimulants, is common and contributes to poor clinical and functional outcomes. Factors such as adverse effects, stigma, complex dosing, abuse potential, and regulatory burdens can all undermine adherence. Viloxazine ER, a once-daily non-stimulant medication, may address multiple barriers to adherence due to its lack of abuse potential, more rapid onset of efficacy, favorable tolerability, and absence of significant cardiovascular risks, potentially supporting better long-term adherence across patient populations. 

References 

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