Stimulants and non-stimulants are the two main groups of ADHD medication. Stimulants, which are based on methylphenidate or amphetamine, act quickly and are the most widely used. Non-stimulants, such as atomoxetine, viloxazine, guanfacine and clonidine, take longer to act, but the CDC notes their effect can last up to 24 hours.
Part of our guide: A Patient’s Guide to Psychiatric Medication
Neither group is right for everyone. The differences that matter most are how quickly the medicine works, how strong the evidence is, the safety warnings on its label, and whether it is a controlled substance.
If you are thinking about suicide or are in crisis: call or text 988 (988 Suicide & Crisis Lifeline), call 911 or go to the nearest ER.
What stimulants are
Stimulants are the best-known and most widely used ADHD medications. The CDC reports that 70 to 80 percent of children with ADHD have fewer symptoms when taking them. They come in short-acting and longer-acting forms and include:
- Methylphenidate, for example Concerta, which is labeled for patients ages 6 to 65.
- Mixed amphetamine salts, for example Adderall XR, labeled for adults and children 6 and older.
- Lisdexamfetamine, for example Vyvanse, labeled for ADHD from age 6 and for moderate to severe binge eating disorder in adults.
Methylphenidate blocks the reuptake of norepinephrine and dopamine. Even so, the labels are candid that the exact way stimulants help ADHD is not known. That uncertainty does not change the fact that they have been studied extensively.
What non-stimulants are
Non-stimulants work through different pathways, and they fall into two broad types.
- Norepinephrine-focused medicines. Atomoxetine and viloxazine are labeled for adults and children 6 and older. Both are thought to work by acting on norepinephrine reuptake.
- Alpha-2 agonists. Guanfacine extended release and clonidine extended release act on alpha-2 receptors. Both can be used alone or added to a stimulant. Their labels base ADHD results on children and teens ages 6 to 17, so ask how that evidence applies if you are an adult. Their labels say neither is a central nervous system stimulant.
Side-by-side comparison
| Stimulants | Non-stimulants | |
|---|---|---|
| Onset | Fast acting | Slower; do not work as quickly as stimulants |
| Duration | Depends on the formulation | Effect can last up to 24 hours |
| Controlled substance | Yes, Schedule II for the products listed here | Atomoxetine, guanfacine ER and clonidine ER labels say no |
| Boxed warning | Abuse, misuse and addiction | Suicidal thoughts for atomoxetine and viloxazine; none on the guanfacine ER and clonidine ER labels |
| Monitoring highlighted on label | Blood pressure, pulse, growth in children, new psychosis or mania | Varies: blood pressure, heart rate, sedation, mood and behavior, liver symptoms for atomoxetine |
What the research says about effectiveness
A major comparison is a 2018 network meta-analysis of 133 double-blind trials, which its authors called the most comprehensive evidence base available at the time. In short-term use, all the included medicines beat placebo on clinician-rated symptoms in children and adolescents. In adults, amphetamines, methylphenidate, bupropion and atomoxetine beat placebo. Head-to-head comparisons favored amphetamines on clinician ratings, while tolerability varied by drug and by age group.
Weighing both benefit and safety, the authors supported methylphenidate in children and adolescents and amphetamines in adults as preferred first choices for short-term treatment. Two limits matter here. Confidence in many of the comparisons was low, and the researchers did not find enough data at 26 and 52 weeks, so they called for long-term research. Also, viloxazine and some newer options were not part of the picture, so the review does not settle every comparison.
The right choice for one person may differ from what averages suggest. As the CDC puts it, one child may respond well to one medication, but not to another.
Safety: what the labels warn about
Stimulants
- Misuse and addiction. The boxed warning says these medicines have a high potential for abuse and misuse, which can lead to a substance use disorder, overdose and death. Your prescriber should assess your risk first. Keep them secure and never share them.
- Heart and blood pressure. The Concerta label calls for monitoring for hypertension and tachycardia and says to avoid use in people with certain serious heart conditions. Share your personal and family heart history.
- Mental health effects. Stimulants can worsen existing psychosis and may induce a manic or mixed episode in people with bipolar disorder, so screening comes first.
- Growth in children. The label says to closely monitor height and weight in pediatric patients.
Non-stimulants
- Atomoxetine has a boxed warning on suicidal thoughts in pediatric patients, so children and teens need close observation, especially in the first months and after dose changes. Families should report new suicidal thoughts or unusual changes in behavior to the prescriber right away. Its label also warns of rare but severe liver injury. Dark urine, yellow skin or eyes, or unexplained flu-like symptoms should prompt a call right away.
- Viloxazine has a boxed warning on suicidal thoughts and behaviors that calls for closely monitoring all treated patients, adults included. It can also raise heart rate and diastolic blood pressure.
- Guanfacine and clonidine extended release can lower blood pressure and heart rate and cause sleepiness. Stopping either suddenly can cause rebound hypertension, which is a strong reason to make any change only with your prescriber.
Everyday side effects
Serious risks get the attention, but day-to-day side effects often decide whether a medicine works for someone. These lists come from clinical trials and will not apply to everyone.
- Methylphenidate (Concerta), adults: decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight loss, irritability, fast heartbeat and sweating.
- Atomoxetine, children: nausea, vomiting, fatigue, decreased appetite, abdominal pain and sleepiness. In adults, the label lists constipation, dry mouth, nausea, decreased appetite, dizziness, erectile dysfunction and urinary hesitation.
- Guanfacine extended release, children and teens: low blood pressure, sleepiness, fatigue, nausea and lethargy.
Tell your prescriber about these side effects rather than quietly living with them.
Questions that can guide the choice
Your clinician will weigh your history and goals, and the following questions can make that conversation more useful:
- What time of day do symptoms cause the most trouble, and how long do you need coverage?
- Have you ever had a substance use problem, or is anyone at home at risk of misusing medicine?
- Do you have any heart problems, high blood pressure, tics, anxiety, mood symptoms or sleep trouble?
- For a child: how are appetite, height and weight tracking?
- How would a slower-acting medicine fit what you need right now?
- What would you want to see improve, and how will you both measure it?
Children under 6 are a separate conversation. The CDC says parent training in behavior management is the first line of treatment, before medication is tried, for that age group. For children 6 and older, it reports that the American Academy of Pediatrics recommends combining medication with behavior therapy. See medication versus therapy for ADHD for more on that balance, and what changes between children and adults.
Making changes safely
Finding the right fit may take adjustments, because the CDC says providers should work to balance benefits against side effects and may need to try different medications and doses. Make those changes only with your prescriber. That includes stopping, skipping or restarting a medication and taking someone else's. Availability can also shape the plan, so see refills, prior authorizations and shortages if a pharmacy cannot fill your prescription.
Where to go from here
If you are comparing options for yourself or your child, ADHD care for adults and children at Mind Body Seven includes this discussion. You can request a consultation, and the intake team confirms fit, scheduling and costs.
FAQs
Can stimulants and non-stimulants be taken together?
Sometimes. Guanfacine extended release and clonidine extended release are labeled both on their own and as add-ons to stimulant medication. Whether that suits you is a question for your prescriber.
Will ADHD medication show up on a drug test?
Stimulants contain amphetamine or methylphenidate, and testing rules vary by employer, school and test type. If you expect a test, tell the testing organization about your prescription and ask your prescriber what documentation may help.
Is non-stimulant medication safer because it is not a stimulant?
Its risks are different and it does have risks. Atomoxetine and viloxazine carry boxed warnings, and guanfacine can lower blood pressure. A non-stimulant lowers concern about stimulant misuse, which may matter for some people, but it still needs monitoring.
