<!-- Definition and medical uses -->
Viloxazine, sold under the brand name Qelbree among others, is a selective norepinephrine reuptake inhibitor medication that is indicated in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. It was marketed for almost 30years as an antidepressant for the treatment of depression before being discontinued and subsequently repurposed as a treatment for ADHD. Viloxazine is a non-stimulant medication; it has no known misuse liability and is not a controlled substance.
Depression
Viloxazine was previously marketed as an antidepressant for the treatment of major depressive disorder. Other common side effects include nausea, vomiting, epigastric pain, insomnia, Incidence of some side effects, including headache and drowsiness, appear to be dose-dependent. In the treatment of depression, viloxazine is more tolerable than tricyclic antidepressants such as imipramine and amitriptyline.
Interactions
Viloxazine increased plasma levels of phenytoin by an average of 37%. It also was known to significantly increase plasma levels of theophylline and decrease its clearance from the body, sometimes resulting in accidental overdose of theophylline.
Pharmacology
Pharmacodynamics
Viloxazine acts as a selective norepinephrine reuptake inhibitor (sNRI) and this is believed to be responsible for its therapeutic effectiveness in the treatment of conditions like ADHD and depression.
More recent research has found that the pharmacodynamics of viloxazine may be more complex than previously assumed. In 2020, viloxazine was reported to have significant affinity for the serotonin 5-HT<sub>2B</sub> and 5-HT<sub>2C</sub> receptors (K<sub>i</sub> = 3,900 nM and 6,400 nM) and to act as an antagonist and agonist of these receptors, respectively. It also showed weak antagonistic activity at the serotonin 5-HT<sub>7</sub> receptor and the α<sub>1B</sub>- and β<sub>2</sub>-adrenergic receptors.
Analogues
Analogues of viloxazine include indeloxazine, reboxetine, and teniloxazine, among others.
History
Viloxazine was discovered by scientists at Imperial Chemical Industries when they recognized that some beta blockers inhibited serotonin reuptake inhibitor activity in the brain at high doses. To improve the ability of their compounds to cross the blood brain barrier, they changed the ethanolamine side chain of beta blockers to a morpholine ring, leading to the synthesis of viloxazine. It was first described in the scientific literature as early as 1972.
The medication was first marketed in 1974. Viloxazine was not approved for medical use by the FDA. In 1984, the FDA granted the medication an orphan designation for treatment of cataplexy and narcolepsy with the tentative brand name Catatrol. For unknown reasons however, it was never approved or introduced for these uses in the United States. Viloxazine was approved for the treatment of ADHD in the United States in April 2021.
Society and culture
Brand names
Viloxazine has been marketed under the brand names Emovit, Qelbree, Vicilan, Viloxazin, Viloxazina, Viloxazinum, Vivalan, and Vivarint.
Research
Viloxazine has undergone two randomized controlled trials for nocturnal enuresis (bedwetting) in children, both of those times versus imipramine. By 1990, it was seen as a less cardiotoxic alternative to imipramine, and to be especially effective in heavy sleepers.
In narcolepsy, viloxazine has been shown to suppress auxiliary symptoms such as cataplexy and also abnormal sleep-onset REM without significantly improving daytime somnolence. In a cross-over trial (56 participants) viloxazine significantly reduced EDS and cataplexy.
Viloxazine has also been studied for the treatment of alcoholism, with some success.
Viloxazine did not demonstrate efficacy in a double-blind randomized controlled trial versus amisulpride in the treatment of dysthymia.