Frequently Asked Questions

Yes. In the full analysis set of 150 adults with ADHD and prominent depression and/or anxiety symptoms, the mean change from baseline to week 14/end of study in AISRS total score was -17.3 points (SD 11.34; P < .0001), corresponding to a 45.3% mean reduction from baseline. On the patient-reported ASRSv1.1-SC, the mean change was -28.4 points (SD 14.89; P < .0001), a 50.9% mean reduction.

Clinically meaningful ADHD improvement was common: 71.8% of participants achieved at least a 30% reduction in AISRS total score, and 45.6% achieved at least a 50% reduction by week 14/end of study.

Yes. Depression scores decreased significantly over 14 weeks in this open-label trial. At week 14/end of study, the mean change from baseline was -15.5 points on the MADRS (SD 7.12) and -10.6 points on the PHQ-8 (SD 5.24), with both reported as nominally significant at all study visits (all P < .0001).

At week 14/end of study, 57.5% of participants achieved at least a 50% reduction in MADRS total score and 78.4% achieved at least a 50% reduction in PHQ-8 total score. Depression remission was reported in 28.3% by MADRS criteria and 48.6% by PHQ-8 criteria.

Yes. Anxiety symptoms also decreased significantly in this study. At week 14/end of study, the mean change from baseline was -14.2 points on the HAM-A (SD 5.79) and -8.5 points on the GAD-7 (SD 5.33), and anxiety scores were nominally significantly reduced at all study visits (all P < .0001).

By week 14/end of study, 70.8% of participants achieved at least a 50% reduction in HAM-A total score and 67.6% achieved at least a 50% reduction in GAD-7 total score. Anxiety remission was achieved by 24.2% on HAM-A criteria and 43.2% on GAD-7 criteria.

In this study, yes. The trial allowed concomitant stimulant medications for ADHD and medications for other medical or psychiatric conditions, including depression or anxiety. During the study, 28.6% of participants took stimulants, 44.7% took antidepressants, and 14.9% took anxiolytic and/or hypnotic medications.

The authors reported that viloxazine ER was generally well tolerated among both participants who were and were not receiving stimulants, and they described the preliminary safety findings as encouraging. However, they also stated that careful monitoring is important and that the impact of concomitant medication patterns on efficacy and safety has not yet been evaluated.

Treatment-emergent adverse events occurred in 70.8% of participants, and most were mild to moderate in severity. The most common adverse events reported in at least 5% of participants were nausea, insomnia, constipation, headache, fatigue, somnolence, decreased appetite, migraine, and dry mouth.

Adverse events led to discontinuation in 24 participants (14.9%). Events leading to discontinuation in at least 3 participants were insomnia (n=8), nausea (n=5), decreased appetite (n=4), migraine (n=4), somnolence (n=4), dizziness (n=3), and suicidal ideation (n=3).

Yes. Five participants (3.1%) reported treatment-emergent adverse events of suicidal ideation, and 3 of those participants withdrew from the trial because of these events. The proportion of participants reporting suicidal ideation on the C-SSRS during the treatment period was 5.3%.

Two cases of suicidal ideation were serious, moderate in severity, considered related to treatment, and both were reported on day 3 of study treatment. The article states that suicidal ideation resolved in all cases, and no suicidal behavior was reported during viloxazine ER treatment.

Yes. The study reported modest mean increases in systolic blood pressure, diastolic blood pressure, and pulse rate at all visits, along with a mean decrease in body weight at all visits. At week 14/end of study, 20.0% of participants had a greater than 15 mm Hg increase in systolic blood pressure, 13.3% had a greater than 15 mm Hg increase in diastolic blood pressure, and 10.2% had a greater than 20 beats per minute increase in pulse rate.

These changes were seldom recorded as treatment-emergent adverse events. Reported cardiovascular-related adverse events included heart rate increased in 3 participants (1.9%), hypertension in 2 (1.2%), palpitations in 1 (0.6%), and blood pressure increased in 1 (0.6%).

Yes. The study found significant mean reductions from baseline in BRIEF-A Global Executive Composite, Behavioral Regulation Index, and Metacognition Index T-scores, as well as in PSQI global scores, indicating improvement in executive functioning and sleep.

Work productivity impairment also improved at week 14/end of study. Mean changes from baseline in WPAI:SHP percentages were -5.89 for absenteeism (SD 20.170; P<.05), -23.08 for presenteeism (SD 26.072; P<.0001), -36.06 for regular activity impairment (SD 24.230; P<.0001), and -22.32 for overall work productivity impairment (SD 26.915; P<.0001).

This was a phase 4, open-label, flexible-dose, decentralized, single-arm trial in adults with ADHD and comorbid depression and/or anxiety symptoms. A total of 161 participants received viloxazine ER, and 104 (64.6%) completed the study; efficacy analyses were based on a full analysis set of 150 participants. The treatment period lasted 14 weeks, after a 4-week screening period, with a 1-week safety follow-up.

The design was intended to reflect real-world use, including allowance for concomitant psychiatric medications and remote participation through televisits and a mobile app. However, because the study was open-label and had no comparator group, the authors state that the results should be interpreted descriptively and that treatment effects may be overestimated.

The main limitations were the open-label design, the absence of a comparator group, and the lack of long-term follow-up. The authors also note that the analyses were descriptive rather than confirmatory, no multiplicity adjustments were applied, and statistical findings across visits should be interpreted descriptively.

Additional limitations included that the study was not designed to determine whether improvements in depression or anxiety were direct effects of viloxazine ER or secondary to ADHD improvement, and concomitant medication changes were not yet evaluated for their impact on efficacy or safety. The decentralized design may also introduce challenges such as potential difficulty obtaining patient-reported outcomes consistently, self-selection bias from online recruitment, exclusion of people without smartphone or internet access, and limited generalizability because the sample was mostly White and female.