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Investigators studied patients who started out taking atomoxetine and, after a washout period, initiated treatment with viloxazine. Participants’ ADHD symptoms were assessed prior to initiation of each treatment and after 4 weeks.
Children and adults showed significantly larger improvement in inattentiveness and hyperactivity/impulsivity when taking viloxazine vs. atomoxetine, with almost all patients preferring the former to the latter, according to results of the study.
In addition, close to one half of the study participants were taking a prior stimulant, and 85% were able to taper off stimulant treatment. Viloxazine’s effects were more rapid than were those of atomoxetine.
“It is timely to have a rapidly acting, and highly effective nonstimulant option across the full spectrum of ADHD symptoms, for both children and adults, in light of recent stimulant shortages and the new [Food and Drug Administration] boxed warnings regarding increased mortality associated with overuse of stimulants” study investigator Maxwell Z. Price, a medical student at Hackensack Meridian School of Medicine, Nutley, N.J., said in an interview.
Nonstimulant treatment options
Study coauthor Richard L. Price, MD, noted that the study was conducted to find a more acceptable alternative to psychostimulant treatments for ADHD, which are currently considered the “gold standard.”
Although they are effective, said Dr. Price, they are fraught with adverse effects, including appetite suppression, insomnia, exacerbation of mood disorders, anxiety, tics, or misuse.
Atomoxetine, a nonstimulant option, has been around for a few decades and is often used in combination with a stimulant medication. However, he said, the drug has a mild effect, requires frequent dosage adjustment, takes a long time to work, and people have “soured” on its utility, Dr. Price added.
Like atomoxetine, viloxazine is a selective norepinephrine inhibitor that has been used an antidepressant in Europe for 30 years. It was recently reformulated as an extended-release medication and approved by the FDA for pediatric and adult ADHD.
However, unlike atomoxetine, viloxazine is associated with increased prefrontal cortex 5-hydroxytrytamine, norepinephrine, and dopamine levels in vivo.
There have been no head-to-head trials comparing the two agents. However, even in head-to-head ADHD medication trials, the agents that are under investigation are typically compared in matched patients. The current investigators wanted to compare the two agents in the same patients whose insurers mandate a trial of generic atomoxetine prior to covering branded viloxazine.
“We wanted to find out whether patients taking atomoxetine for ADHD combined type would experience improvement in ADHD symptoms following voluntary, open-label switch to viloxazine,” said Dr. Price.
The researchers studied 50 patients who presented with ADHD combined type and had no other psychiatric, medical, or substance-related comorbidities or prior exposure to atomoxetine or viloxazine.
The study included 35 children (mean age, 11.9 ± 2.9 years; 94.3% male) and 15 adults (mean age, 29.3 ± 9.0 years; 73.3% male). Of these, 42.9% and 73.3%, respectively, were taking concurrent stimulants.
Patients received mean doses of atomoxetine once daily followed by viloxazine once daily after a 5-day washout period between the two drugs. Participants were seen weekly for titration and monitoring.
At baseline, the pediatric ADHD–Rating Scale 5 (ADHD-RS-5) and the Adult Investigator Symptoms Rating Scale (AISRS) were completed, then again after 4 weeks of treatment with atomoxetine (or upon earlier response or discontinuation due to side effects, whichever came first), and 5 days after discontinuing atomoxetine, which “reestablished the baseline score.” The same protocol was then repeated with viloxazine.