Non-stimulant ADHD medications ranked

The four main non-stimulant ADHD medications compared: atomoxetine, viloxazine (Qelbree), guanfacine ER, clonidine ER (including Onyda XR). Efficacy, side effect profiles, and when to choose each.

Medically reviewed by Shariq Refai, MD, MBA Last reviewed: July 2026

Ranking by role

Atomoxetine (Strattera, generic):

Norepinephrine reuptake inhibitor
Once-daily or twice-daily oral
Non-controlled, no scheduling
Effect over 4 to 8 weeks (slow onset)
Standard adult 40 to 100 mg, pediatric weight-based
Best evidence base of non-stimulants
CYP2D6 substrate; poor metabolizers get higher levels and more side effects
Suicidal ideation warning (pediatric)

Qelbree (viloxazine ER):

Multimodal serotonin plus norepinephrine
Once-daily oral
Non-controlled
Effect over 2 to 4 weeks
Pediatric 200 to 600 mg, adult 200 to 600 mg
Strong CYP1A2 inhibitor (raises clozapine, olanzapine, duloxetine, caffeine)
Boxed warning for suicidal ideation in pediatrics
Newer, less real-world experience than atomoxetine

Guanfacine ER (Intuniv, generic):

Alpha-2A adrenergic agonist
Once-daily oral
Non-controlled
Effect over 2 to 6 weeks
Pediatric 1 to 4 mg, less well studied in adults but sometimes used
Sedation, orthostasis, dry mouth
Rebound hypertension risk if stopped abruptly

Clonidine ER (Kapvay tablet, Onyda XR liquid):

Alpha-2 agonist (less selective than guanfacine)
Twice-daily tablet or once-daily Onyda XR
Non-controlled
Effect over 1 to 4 weeks
Pediatric 0.1 to 0.4 mg
More sedating than guanfacine
Rebound hypertension risk

When to choose each

Atomoxetine: First-line non-stimulant. Broad efficacy, adult indication, largest evidence base. Choose when a first non-stimulant is needed.

Qelbree: Second-line after atomoxetine failure or intolerance, or when a different mechanism is desired. Useful in adults who want a once-daily option.

Guanfacine ER: For patients with comorbid tics, anxiety, or hyperactivity-predominant presentation. Often preferred when sleep is fine and morning sedation is unwelcome.

Clonidine ER / Onyda XR: For patients with comorbid tics, insomnia, or when sedation at bedtime is desired. Onyda XR specifically for young pediatric patients (age 6+) who cannot swallow tablets.

Comparison with stimulants

Non-stimulants have smaller effect sizes than stimulants in head-to-head meta-analyses. Stimulants remain first-line unless there's a specific reason (side effects, contraindication, family preference, SUD history, tics).

Non-stimulants are chosen when:

Stimulant intolerance (appetite loss, sleep problems, mood irritability, tics, cardiovascular concerns)
Stimulant non-response
SUD history where controlled substance is a concern
Family or patient preference for non-controlled
Comorbid tics (may respond better to alpha-2 agonists)
Comorbid anxiety (may respond better to non-stimulants)

Combination with stimulants

Common: stimulant plus guanfacine or clonidine ER for evening or "off-window" symptoms, or for tics that emerge on stimulant. Atomoxetine plus stimulant is less common but has evidence. Qelbree plus stimulant is theoretically possible but not well studied.

Common questions

How long until non-stimulants work? Atomoxetine 4 to 8 weeks. Qelbree 2 to 4 weeks. Guanfacine and clonidine ER 1 to 6 weeks. All slower than stimulants (days).

Are non-stimulants as effective as stimulants? No. Effect sizes are consistently smaller in head-to-head trials and meta-analyses. Stimulants remain first-line for most patients unless a specific reason to use non-stimulants.

Which non-stimulant is best for adults? Atomoxetine has the largest adult evidence base. Qelbree has adult indication. Guanfacine ER is used off-label in adults with some evidence.

Should I try atomoxetine before Qelbree? Usually yes given larger evidence base and generic availability. Move to Qelbree if atomoxetine fails or causes side effects.

Do non-stimulants have abuse potential? None have documented abuse potential. All are non-controlled substances. This is a real advantage for patients with SUD history.

Which non-stimulant helps tics? Guanfacine and clonidine ER often improve tics rather than worsen them. Atomoxetine and Qelbree have less specific effect on tics.

What about growth on non-stimulants? Atomoxetine has modest growth suppression in trials, smaller than stimulants. Guanfacine and clonidine have less. Qelbree has some data suggesting less growth effect.

Sources

Wolraich ML, Hagan JF, Allan C, et al. Clinical practice guideline for the diagnosis, evaluation, and treatment of ADHD in children and adolescents. Pediatrics. 2019;144(4):e20192528.
FDA prescribing information for atomoxetine, Qelbree, Intuniv, Kapvay, and Onyda XR.
Cortese S, Adamo N, Del Giovane C, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018;5(9):727-738.

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