Immediate Impact

In January of 2025, Supernus received an update to Section 12.2 of their Viloxazine-ER (Qelbree) package insert to include the original data on inhibiting the norepinephrine transporter and also added that viloxazine is a partial agonist for serotonin 2C. ​

"12.2 Pharmacodynamics: Viloxazine binds to and inhibits the norepinephrine transporter (Ki=0.13 μM). In addition, viloxazine binds to and exhibits partial agonist activity at the serotonin 5-HT2C receptor (Ki=0.66 μM)."

This data was added because of studies that demonstrated that viloxazine’s modulation of 5-HT2C improved impulsivity at therapeutically relevant concentrations in animal models and that impulse control was significantly impaired when a 5-HT2C antagonist was added to viloxazine.​

This represents the first time that the pharmacodynamic section of a package insert has been modified by the US Food and Drug Administration (FDA) with new data for a psychotropic medication.​

This represents the first attention-deficit/hyperactivity disorder (ADHD) medication to have data including serotonin modulation in its package insert.

Dr Jain –

Importance to Science: 7
Importance to the Molecule: 8
Importance to the Medication Class: 7

Generally speaking, this is quite a positive move for this medication. First, it is the first and only time the FDA has changed its mechanism of action on any approved medication. Secondly, it helps differentiate it from other non-stimulant medications. On the other hand, this medication is struggling to grab a foothold in the minds of psychiatrists, pediatricians, and general practitioners. While this is a positive scientific movement, I'm not sure it's going to produce a very dramatic change in market share.

Dr Cutler –

Importance to Science: 10
Importance to the Molecule: 10
Importance to the Medication Class: 10

I think this is a very big deal for Supernus and Qelbree and for psychopharmacology in general. It is one of the first times, if not the first time, that the FDA has revised and updated section 12.2 Pharmacodynamics (the medicine’s mechanism of action [MOA] section) in the package insert for a psychiatry medicine, and it is a very good precedent. It helps differentiate viloxazine (Qelbree) from atomoxetine (Strattera).

Dr Sohl –

Importance to Science: 7
Importance to the Molecule: 8
Importance to the Medication Class: 9

Dr Melmed –

Importance to Science: 7
Importance to the Molecule: 8
Importance to the Psychiatry Class: 8

This emphasizes the importance of looking out for a wider range of MOAs of commonly used psychiatric medications. Shedding light on the MOA will help stimulate further research into the use of serotonin modulators. Understanding the impact of serotonin on impulsivity is similarly valuable. Utilization of the data will make it more attractive to prescribers to use first line. Possible overlap of impact on both impulsivity as well as anxiety will also be taken into account by them. This will be an important discussion point with patients.

Dr Mattingly –

Importance to Science: 8
Importance to the Molecule: 10
Importance to the Medication Class: 9

This is of significant scientific importance as the first psychotropic medication to receive an update to its pharmacodynamic section by the FDA. The FDA update included that Qelbree is a partial agonist at 5-HT2C receptors in addition to its original indication as a norepinephrine reuptake inhibitor. The FDA considered data showing that, at therapeutically relevant concentrations, viloxazine modulated the 5-HT2C receptor, and partial agonist effects at this receptor caused a significant improvement in impulse behavior.

As the first and only currently FDA-approved ADHD medication that has been shown to directly modulate serotonin receptors, this is unique for this molecule. It also promotes research into other molecules that modulate serotonin and the potential impact of such modification for both ADHD and common co-occurring conditions.