Non-Stimulant ADHD Medications
Non-stimulant ADHD medications fall into two main drug classes: selective norepinephrine reuptake inhibitors (atomoxetine and viloxazine) and selective α-2 adrenergic agonists (extended-release guanfacine and extended-release clonidine). 1, 2, 3
The Two Primary Classes
Norepinephrine Reuptake Inhibitors
- Atomoxetine (Strattera) - the most extensively studied non-stimulant with FDA approval across the lifespan 2, 4
- Viloxazine extended-release - newer agent approved in 2021 5, 6
α-2 Adrenergic Agonists
- Guanfacine extended-release (Intuniv) - FDA-approved with demonstrated efficacy 1, 2
- Clonidine extended-release (Kapvay) - FDA-approved alternative 1, 2
Efficacy Comparison
Non-stimulants have an effect size of approximately 0.7, which is less robust than stimulants (effect size ~1.0), but still clinically meaningful. 2 Among the non-stimulants, the evidence hierarchy shows atomoxetine has the strongest evidence base, followed by extended-release guanfacine, then extended-release clonidine 2.
Recent meta-analysis data confirms atomoxetine (Hedge's g = -0.48), guanfacine (Hedge's g = -0.66), and viloxazine all demonstrate significantly greater efficacy than placebo in adults 5.
Clinical Context
These medications serve as alternatives when:
- Stimulants cause intolerable side effects
- Inadequate treatment response to stimulants
- Risk of stimulant diversion exists
- Family preference to avoid stimulants
- Certain comorbid conditions are present 3, 6
Non-stimulants can be used either as monotherapy or added to stimulants as augmentation. 3, 6
Important Caveat
While other medications like bupropion and tricyclic antidepressants have been used off-label for ADHD, they are not recommended as standard non-stimulant options and should only be considered as third-line alternatives 3.