How Does Atomoxetine (Strattera) Work? All About Its Mechanism of Action

There’s no shortage of medications to treat attention-deficit hyperactivity disorder (ADHD). 

Stimulants and nonstimulants are the two primary medication groups for ADHD, and there are several options within each group. Examples of stimulants that treat ADHD include amphetamine salts (Adderall) and methylphenidate (Ritalin). The most common nonstimulant option is atomoxetine (Strattera).

Atomoxetine has a unique mechanism of action. Here, we’ll cover how atomoxetine works, how to know if it’s working, and how it compares to stimulants.

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What is atomoxetine?

Atomoxetine is a prescription medication that treats ADHD in adults and children who are at least 6 years old. It’s a nonstimulant medication. Nonstimulants are typically seen as less effective at treating ADHD than stimulant medications. But atomoxetine is considered to be the most effective nonstimulant treatment option.

Atomoxetine comes as an oral capsule that’s taken once or twice a day.

How does atomoxetine work?

Atomoxetine is a norepinephrine reuptake inhibitor (NRI). Exactly how it works isn’t known. But there are some things we do know about its mechanism of action.

Before we talk about how atomoxetine works, however, we need to understand how ADHD affects the brain.

Brain changes in ADHD

Several environmental and genetic factors may contribute to ADHD, as well as imbalances in two neurotransmitters (chemical messengers) in the brain. The two main neurotransmitters involved in causing ADHD symptoms are norepinephrine and dopamine. It’s thought that levels of these neurotransmitters are decreased in people with ADHD.

Atomoxetine effects on norepinephrine and dopamine

Atomoxetine seems to work by boosting norepinephrine levels in the brain. Norepinephrine has several actions in the body, including:

• Increasing heart rate

• Increasing blood pressure

• Breaking down fat

• Increasing blood glucose (sugar)

• Helping you stay awake

• Improving attention and focus 

Typically, norepinephrine is absorbed by your nerve cells after it performs its actions. But atomoxetine blocks a molecule that transports norepinephrine into nerve cells. This frees up more norepinephrine for the brain to use. 

Atomoxetine also boosts dopamine levels in an area of the brain called the prefrontal cortex. Dopamine is involved in managing your mood, attention, and more. 

Good to know: Medications and substances that increase dopamine in a certain area of the brain (the striatum and nucleus accumbens) may lead to dependence and misuse. This increases your risk of developing a substance use disorder. Though atomoxetine boosts dopamine levels, it doesn’t do so in the striatum or nucleus accumbens. So it isn’t known to cause dependence or misuse.

Does atomoxetine start to work immediately?

No, it can take a few weeks for atomoxetine to work. You may start to see ADHD symptoms improve within 1 to 2 weeks of starting it. By 4 to 6 weeks, you should see significant improvement. 

You may continue to see improvement in your ADHD symptoms after the first 6 weeks of treatment. In fact, some research shows that ADHD symptoms may continue to get better for up to 6 to 12 months after starting atomoxetine.

Even if atomoxetine doesn’t work right away, that doesn’t mean it won’t work for you at all. Though it starts working more slowly, it can continue to improve ADHD symptoms over several weeks and months. However, if you haven’t felt any improvement after 4 to 6 weeks, talk to your prescriber. They may want to adjust your dose or try another ADHD medication.

How do you know if atomoxetine is working?

The goal of atomoxetine treatment is to improve your ADHD symptoms. So if you feel that ADHD is having less of an effect on your day-to-day life while taking atomoxetine, this is a good sign.

ADHD symptoms that may improve with atomoxetine include:

• Hyperactivity 

• Irritability

• Sleep problems

• Impulsivity

• Quick mood changes

• Executive functioning skills, like remembering details and the ability to finish tasks

Keep in mind that ADHD symptoms may vary depending on whether you’re an adult, teen, or child. This can be helpful to know if you’re a parent or caregiver trying to find out if atomoxetine is working for someone else.

How does atomoxetine compare to other medications for ADHD?

As mentioned, there are several different medications that treat ADHD, including:

• Short-acting stimulant medications such as mixed amphetamine salts, methylphenidate, and dexmethylphenidate (Focalin)

• Extended-release (ER) stimulants such as lisdexamfetamine (Vyvanse), amphetamine salt combo ER (Adderall XR), and methylphenidate ER (Concerta)

• Another NRI, Qelbree (viloxazine)

• Alpha-2 adrenergic agonists such as guanfacine ER (Intuniv ER) and clonidine ER (Kapvay)

Long-acting stimulants are generally first-choice medications for adult ADHD. But if these aren’t a good option for you, NRIs like atomoxetine or Qelbree may be good choices. Other medications, like the antidepressant bupropion (Wellbutrin SR, Wellbutrin XR),

may also help with ADHD if you also have depression. But this is an off-label use.

Stimulants are also a first-choice medication for ADHD in children. If stimulants don’t work or cause too many side effects, atomoxetine is a second-choice option. Guanfacine ER and clonidine ER are considered third-choice options.

Atomoxetine versus stimulant medications for ADHD

Although stimulant medications are considered first-choice medications for ADHD, atomoxetine may be preferred in some cases. It may be helpful to understand the key differences between atomoxetine versus stimulants. There are several factors to consider, including:

• How quickly the medications work: Stimulant medications begin working the day you start taking them. This is faster than atomoxetine, which can take several weeks to work. So if you want a quick response, stimulants may be a better choice.

• Potential for dependence and misuse: Stimulants like Adderall can lead to dependence, misuse, and overdose. And people with a history of substance use have a greater likelihood of developing stimulant use disorder. If this applies to you, atomoxetine may be a better choice, since it doesn’t have these risks.

• Differences in side effects: Atomoxetine side effects are different from side effects from stimulants, like lisdexamfetamine and methylphenidate. Knowing about the possible side effects of these medications can help you and your healthcare team decide which medication is best for you.

• Differences in drug interactions: Atomoxetine interactions are different from interactions with stimulants, like Adderall and methylphenidate products. Knowing about possible drug interactions can help you and your healthcare team determine which medication option is safest for you.

If your healthcare professional thinks you could benefit from ADHD medication, they’ll discuss your options with you. They can help you weigh the risks and benefits of various ADHD medications. Make sure they know your full health history. And provide them with a list of medications and supplements you take. This will help them check for drug interactions.

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Written by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

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