Non-Stimulant ADHD Medications Compared

Approval ages, boxed warnings and common side effects below come from each drug's current FDA label on DailyMed. 'Off-label' means the FDA hasn't approved the drug for that use or age. Clinicians can still prescribe it when the evidence and your situation support it, and they should tell you when they do.

Atomoxetine is approved for ADHD in adults and children 6 and older. Its label says the exact mechanism is unknown but is thought to involve blocking the norepinephrine transporter. It isn't a controlled substance, and in an abuse-potential study in adults it showed no stimulant or euphoric effects compared with placebo (Strattera label, section 9).

It works more gradually than a stimulant. A review of atomoxetine trials found it can start to help within 1 to 2 weeks, with response that keeps building for 24 weeks or longer (Clemow and Bushe, 2015). It is taken once or twice a day. For a week-by-week look, see how long Strattera takes to work.

Its boxed warning: atomoxetine raised the risk of suicidal thinking in children and teens in short-term studies, so they are watched closely, especially in the first months and after dose changes. The label also warns about increases in blood pressure and heart rate. Common side effects in adults include constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction and urinary hesitation.

Viloxazine extended-release is approved for ADHD in adults and children 6 and older and is taken once a day. Its label says it is thought to work by blocking norepinephrine reuptake; it also acts on a serotonin receptor (5-HT2C).

It isn't a controlled substance. When the FDA reviewed it, the agency's Controlled Substance Staff found no concerning level of abuse potential and recommended it not be scheduled (FDA review, NDA 211964).

Its boxed warning covers suicidal thoughts and behaviors, which were reported more often with viloxazine than with placebo in clinical studies, so everyone taking it is monitored. Viloxazine strongly blocks the liver enzyme CYP1A2, which raises levels of some other medicines, so your clinician reviews everything you take. Common side effects in adults include insomnia, headache, sleepiness, fatigue, nausea, decreased appetite, dry mouth and constipation.

Guanfacine extended-release and clonidine extended-release act on alpha-2 adrenergic receptors in the brain. Neither is a stimulant, and their labels say their mechanism in ADHD isn't known. Both are approved for ADHD on the strength of studies in ages 6 to 17, alone or added to a stimulant. Use in adults is off-label: a 2023 meta-analysis found just two adult trials of guanfacine, which pooled showed benefit over placebo (Radonjić et al., 2023), and NICE advises against guanfacine for adults without advice from a tertiary ADHD service.

Both can lower blood pressure and heart rate and cause sleepiness, so your clinician checks vital signs. Intuniv is taken once a day; clonidine ER is taken twice a day, with an equal or larger dose at bedtime. Stopping either suddenly can cause rebound high blood pressure, so the dose is tapered.

Clonidine isn't a controlled substance, and its ADHD label lists no known abuse potential. Some people who use opioids misuse it, though, so prescribers ask about substance use before starting it (Dennison, 2001).

Bupropion is an antidepressant approved for depression and seasonal affective disorder, not ADHD. A Cochrane review of six small trials in adults found low-quality evidence that it reduces ADHD symptoms (Verbeeck et al., 2017). Like other antidepressants it carries a boxed warning about suicidal thoughts in children, teens and young adults, and it isn't used in people with a seizure disorder or a current or past eating disorder (bulimia or anorexia).

Off-label prescribing is legal and common when the evidence supports it. Your clinician should tell you when a prescription is off-label and why.

On average, no. A 2018 network meta-analysis of 133 trials found that in adults, amphetamines, methylphenidate, bupropion and atomoxetine all beat placebo, and amphetamines had the largest effect; head to head, amphetamines did better than atomoxetine (Cortese et al., 2018). A 2023 meta-analysis of non-stimulants in adults found atomoxetine, guanfacine and viloxazine all better than placebo (Radonjić et al., 2023).

Averages don't decide what suits one person. Reasons you and your clinician might choose a non-stimulant include:

• Stimulant side effects you couldn't tolerate, or symptoms that didn't improve on stimulants (when NICE recommends atomoxetine for adults)
• A preference not to take a controlled substance
• A substance-use history that makes a controlled substance a poor fit
• Not being able to get a stimulant by telehealth where you live (see below)
• Adding guanfacine ER or clonidine ER to a stimulant, which their labels cover for ages 6 to 17

Non-stimulants aren't controlled substances, so the federal limits on prescribing controlled substances by telemedicine don't apply to them. Stimulants are different. Federal telehealth rules for controlled substances are temporary through Dec 31, 2026 and may change.

We can't prescribe controlled substances, including stimulants, in Alabama, Arkansas, Hawaii, Louisiana, Maine, Massachusetts, Minnesota, Missouri, Oklahoma, Pennsylvania or West Virginia. You can still be evaluated there, and a non-stimulant may be an option if it fits. In Georgia, call (702) 848-2256 to schedule; Georgia requires an in-person visit within 12 months.

Wherever you are, an evaluation comes first. Your clinician decides whether any medication fits, and no specific medication is guaranteed.

Choosing an ADHD medication starts with confirming the diagnosis. ADHD symptoms overlap with anxiety, depression and sleep problems, and the treatment differs for each. An ADHD evaluation covers your symptoms since childhood, how you're doing now, your medical history and any other conditions.

Your evaluation is with a licensed psychiatric clinician (physician, nurse practitioner or physician assistant, depending on your state). If a non-stimulant becomes part of the plan, follow-up visits check how it's working and any side effects, since these medications take weeks to judge. ADHD treatment covers the rest of the plan, and how telehealth psychiatry works explains the visits.