The effects of atomoxetine (Strattera) on attention and impulsiveness make this drug an important option in ADHD treatment. It also has far less potential for abuse compared to other ADHD medications. Read on to learn how it works and what safety issues to look out for.
What is Atomoxetine?
Atomoxetine (brand name Strattera) is a prescription medication that is used primarily used to treat attention deficit hyperactivity disorder (ADHD).
Originally developed as an antidepressant, atomoxetine was approved in 2002 by the FDA for the treatment of ADHD in children and adults [1].
Is Atomoxetine a Stimulant?
Atomoxetine is unique among ADHD medications because it is not considered a stimulant. Other ADHD drugs, such as Adderall or Ritalin, are classified as Schedule II drugs by the FDA, meaning they have a high risk for abuse [2].
As a non-stimulant, atomoxetine has a minimal risk of drug abuse. The drawback is that atomoxetine appears to be less effective for ADHD symptoms compared to stimulant medications, according to research [3, 4].
Atomoxetine has a lower risk for drug abuse because it primarily works on only one neurotransmitter – norepinephrine. Stimulant medications typically affect several other neurotransmitters, including dopamine and serotonin [1].
How Does Atomoxetine Work?
Brain cells (neurons) communicate with each other by releasing molecules into a small area between them called the synaptic cleft. The molecules they release are called neurotransmitters, such as dopamine, serotonin, and norepinephrine [5].
Normally, special transporters will remove neurotransmitters from the synaptic cleft once they have had their intended effect. However, atomoxetine works by blocking the transporter that removes norepinephrine. This allows norepinephrine to act longer and have a greater effect [1].
Atomoxetine specifically targets the prefrontal cortex area of the brain. This region of the brain is responsible for various functions including planning, decision making, and memory [1, 6].
There is also evidence that atomoxetine may block dopamine reuptake in the prefrontal cortex. More importantly, it does not appear to affect dopamine levels in the reward center of the brain. This may, in part, explain why atomoxetine is less addictive than other ADHD medications [7].
Uses of Atomoxetine
FDA-Approved Uses
ADHD
Attention deficit hyperactivity disorder (ADHD) is a common mental disorder in children and adults that causes poor focus and impulse control and excessive activity [8].
Atomoxetine is FDA-approved for the treatment of ADHD.
A large number of studies have established the effectiveness of atomoxetine in ADHD. Research consistently shows that atomoxetine reduces ADHD symptoms and improves quality of life in children and adults [9, 10, 2, 11].
However, atomoxetine is usually not the first ADHD medication that doctors try. First-line medications for ADHD are typically stimulant drugs, such as methylphenidate (Ritalin) or amphetamines (Adderall). Studies show that the extended-release forms of these drugs are significantly more effective than atomoxetine for treating ADHD [9, 2, 12, 3].
Unlike other ADHD medications, atomoxetine is not considered a stimulant. Ritalin, Adderall, and Vyvanse are all stimulants that may have an addictive effect. This makes atomoxetine useful when drug abuse and addiction is a concern [8, 2].
ADHD with Other Mental Disorders
ADHD is commonly associated with other psychiatric issues. In fact, 87% of adults with ADHD also have a related mental disorder [13].
A review of 50 clinical studies examined atomoxetine’s role in those with ADHD and an additional mental disorder. Specifically, researchers looked at anxiety, depression, and substance use disorder. According to the review, atomoxetine was still effective in ADHD and did not negatively affect other mental conditions, making it a potential option in these cases [13].
Research is investigating atomoxetine in other simultaneous disorders including:
Areas of Research
Research is exploring the use of atomoxetine for several other health conditions. Some of these areas of research are detailed below. However, none of these uses are FDA-approved and are presented for informational purposes only. Always take atomoxetine as directed by your doctor.
Addiction
Although the harmful effects of addiction are evident, the cause of addictive behavior is less clear [20].
One theory is that impairments to attention, memory, and focus play a key role in addiction. Many addictive drugs can lead to cognitive impairments as well, which potentially creates a vicious cycle of drug abuse [20].
These impairments are sometimes similar to ADHD symptoms. In fact, research shows that ADHD is a strong risk factor for substance abuse in adults [20, 21].
Research is exploring the use of cognitive-enhancing drugs as a treatment for substance use disorders [20].
Studies in animals and humans have found that atomoxetine may be helpful in various addictions, including:
According to research, atomoxetine may work by reducing impulsive and risk-seeking behaviors. By potentially improving focus and attention, individuals may better ignore drug-related triggers [31, 32, 23, 28, 29].
However, this is based on small clinical trials and animal studies. No strong clinical trials have fully evaluated the effectiveness of atomoxetine in any type of substance use disorder.
Parkinson’s Disease
Parkinson’s disease primarily affects movement, but it can also lead to behavioral and cognitive issues [33].
Parkinson’s is associated with reduced dopamine levels due to the loss of brain cells. Drugs that increase dopamine in the brain are the primary treatment for Parkinson’s. These drugs help alleviate movement symptoms but do not improve cognitive problems [34].
There is some evidence that drugs that alter norepinephrine levels may help with the non-movement symptoms of Parkinson’s [34].
A systematic review of 7 clinical trials suggests that atomoxetine may improve cognitive function in Parkinson’s disease. Specifically, there were improvements in impulse control and risk-taking behavior [35].
Brain imaging studies also reveal that atomoxetine may promote the growth of connections in the brain [36, 37, 38].
However, studies exploring atomoxetine’s use in other symptoms have not been as successful. The drug does not appear to be effective for movement problems and depression associated with Parkinson’s [39, 40].
Hoarding Disorder
Compulsive hoarding is a mental disorder that can lead to dangerous living conditions and serious health risks [41].
Hoarding is a fairly new disorder – it was only in 2013 that it was recognized as its own distinct mental condition. Previously, hoarding was classified as a symptom of other conditions, like OCD [42].
Hoarding occurs more frequently in people with mental disorders, such as depression and ADHD. This has led researchers to explore the use of ADHD medications in hoarding disorder [43].
One study looked at 12 patients diagnosed with hoarding disorder. Researchers found that atomoxetine reduces hoarding severity by an average of 41.3%. Six of the patients were full responders, meaning their symptoms were reduced by at least 35%. The most improved symptoms were inattentiveness and impulse control [43].
Post Stroke Outcomes
A stroke happens when blood flow to the brain is disrupted, which can lead to permanent brain injury. This damage can have debilitating effects for stroke survivors. These effects include trouble with movement, thinking, and speech to name a few [44, 45].
Research has found that norepinephrine plays a role in brain plasticity, which is the brain’s ability to change and adapt. This has prompted research into atomoxetine’s role in plasticity and potential benefits in stroke survivors [46, 47].
One area of interest is atomoxetine’s effect on movement problems caused by stroke. According to a pilot study of 12 people, atomoxetine may improve movement when combined with physical training [48].
Stroke can also cause aphasia, which is a condition that affects speech and the ability to read or write. A small study of 4 people with post-stroke aphasia suggests that atomoxetine improves language function [49].
Eating Disorders
A 10-week randomized placebo-controlled trial of 40 patients with binge-eating disorder found that atomoxetine significantly reduces binge-eating frequency compared to placebo [50].
Atomoxetine Safety
Side Effects
Atomoxetine is generally well-tolerated in children and adults. According to studies, the majority of side effects are usually mild and few people discontinue therapy due to side effects [2].
Below are some reported side effects of atomoxetine. If any side effects persist or worsen, let your doctor know. This is not a complete list of possible side effects. Tell your doctor if you experience any serious side effects or notice any effects not listed here.
Some common side effects include [2]:
- Headache
- Stomach pain
- Decreased appetite
- Vomiting
- Sleepiness
- Nausea
- Fatigue
- Constipation
- Dry mouth
Some serious side effects include [51]:
- Difficulty urinating
- Dark urine
- Irregular heartbeat
- Fainting
- Persistent nausea or vomiting
- Yellowing of the eyes or skin
- Signs of an allergic reaction (rash, swelling, or trouble breathing)
Atomoxetine shares similar side effects with stimulant ADHD medications. However, atomoxetine is associated with sleepiness, while insomnia is more common in stimulants [2].
Side effects tend to appear early, usually within 1 week of starting atomoxetine. Most side effects typically resolve within 4 weeks [52, 53].
Warnings
Suicidal Behavior
The FDA has warned that atomoxetine may increase the risk of suicide. This decision was based on an analysis of 14 trials that showed an increased risk of suicidal behavior in children, although the incidence appears to be extremely rare [54].
Those taking atomoxetine should be monitored and any changes in behavior should be reported to a doctor.
Heart Effects
Multiple studies show that atomoxetine moderately increases heart rate and blood pressure. Long-term safety research reveals that these heart effects usually diminish over time. However, about 2% of patients still discontinue atomoxetine due to heart effects [55, 56, 57].
Atomoxetine may also negatively impact the QT interval, which is a measurement of the electrical activity of the heart [58, 59, 60].
The FDA recommends avoiding the use of atomoxetine in children or adults with known heart problems [51].
Liver Injury
Atomoxetine is associated with rare cases of liver injury. In an analysis of ~8k case reports, there were 351 reports of liver-related side effects. There were also 3 reports of liver injury where atomoxetine was a probable cause [61].
According to the FDA, atomoxetine should be stopped in patients who show any signs of liver injury [61, 51].
Contraindications
Atomoxetine should not be taken in the following cases [62]:
- Hypersensitivity to atomoxetine or any of its components.
- Monoamine Oxidase Inhibitors (MAOIs) should not be taken within 2 weeks before starting or stopping atomoxetine.
- People with narrow-angle glaucoma.
- People with pheochromocytoma or history of pheochromocytoma
Pregnancy and Breastfeeding Considerations
Due to a lack of clinical research, it’s unclear how atomoxetine affects the fetus. Evidence from some animal studies suggests there may be some negative effects. Atomoxetine should only be used during pregnancy if a doctor determines that the benefits outweigh risks [63].
It is also unclear if atomoxetine is safe to use while breastfeeding. Again, a doctor will decide if the benefits outweigh the risks [63].
Drug Interactions
The following drugs have been reported to interact with atomoxetine. However, this is not a complete list, let your doctor know of all the medications you are currently taking to avoid any unexpected interactions.
- Monoamine oxidase inhibitors (MAOIs)
- Dopamine
- Albuterol
- CYP2D6 inhibitors, such as fluoxetine, bupropion, paroxetine
Dosage
The dosing of atomoxetine can vary. Always take this medication as directed by a doctor.
Atomoxetine comes in capsule form with strengths that range from 10 mg to 100 mg.
For children and teens that weigh less than 70 kg, the FDA recommends a starting dose of 0.5 mg/kg each day. After a minimum of 3 days, the dose should be increased to about 1.2 mg/kg [1].
For children over 70 kg and adults, the starting dose is 40 mg, which should eventually be increased to 80 mg. The dose can be increased to a max of 100 mg per day [1].
Atomoxetine can be taken in a single daily dose or divided evenly into a morning and evening dose.
Atomoxetine can be stopped abruptly without serious negative effects, which is an advantage it has over similar ADHD medications. However, always talk to your doctor first before discontinuing this medication [1].
For those with impaired liver function, the dose can be reduced by 50% to 75% [1].
Poor metabolizers and people taking medications that inhibit CYP2D6 may need a dose adjustment. In this case, the starting dose is 0.5 mg/kg each day. The dose is only increased if symptoms do not improve after 4 weeks [1].
Genetics
Atomoxetine is metabolized by the enzyme CYP2D6. This enzyme is responsible for inactivating drug molecules so they can be removed from the body [1].
The function of CYP2D6 varies from person to person, depending on genetics. Some genetic variations allow people to clear atomoxetine from their bodies very quickly. Others metabolize atomoxetine very slowly, leading to more drug exposure [1].
Based on some studies, a slow metabolizer may have drug levels that are 8 times higher than fast metabolizers [1, 64].
Population studies have found that certain ethnicities, like Chinese and Japanese, tend to be slow metabolizers [1].
This genetic difference is clinically important. Slow metabolizers experience significantly more side effects. On the other hand, fast metabolizers may require higher doses for the drug to be effective [65].
Some SNPs associated with CYP2D6 include:
Takeaway
Atomoxetine is primarily used for the treatment of ADHD, although research is exploring its use in other conditions, such as addiction, Parkinson’s, and eating disorders. Atomoxetine is generally well tolerated, but is associated with rare cases of liver injury, serious heart problems, and increased risk of suicide in children.
