The effects of atomoxetine (Strattera) on attention and impulsiveness makes the drug an important option in ADHD treatment. People seeking a “smart drug” have also taken notice of atomoxetine’s cognitive-enhancing effects. Read on to learn how it works and what safety issues to look out for.

Disclaimer: By writing this post, we are not recommending this drug. Some of our readers who were already taking the drug requested that we commission a post on it, and we are simply providing information that is available in the clinical and scientific literature. Please discuss your medications with your doctor.

What is Atomoxetine?

Atomoxetine (brand name Strattera) is a medication that is used for the treatment of ADHD. The patent for Strattera recently ran out, so the drug will soon face generic competition.

Originally developed as an antidepressant, atomoxetine was approved by the FDA to treat ADHD in 2002 [1].

Atomoxetine is classified as a norepinephrine reuptake inhibitor and increases norepinephrine levels in the brain. Norepinephrine is most known for its role in the body’s fight-or-flight response [1].

Is Atomoxetine a Stimulant?

Research shows atomoxetine is effective at reducing ADHD symptoms in children and adults. It also is one of the few ADHD medications that is not considered a stimulant. As a non-stimulant, atomoxetine has minimal risk for drug abuse [2].

Although atomoxetine is only FDA approved for ADHD, it has shown potential in other conditions. Some of these include addiction, Parkinson’s disease, and hoarding disorder [3, 4, 5].

There is a growing interest in atomoxetine’s nootropic potential. Its effect on focus makes it appealing for those wishing to boost their brain function.

Common side effects of atomoxetine include headache, stomach pain, and sleepiness. The FDA has also issued several safety warnings regarding suicidal behavior, heart effects, and liver injury [2].

Genetic factors also play a large role in side effects and drug effectiveness [1].

Mechanism of Action

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 [6].

Normally, special transporters will remove neurotransmitters from the synaptic cleft. Drugs like atomoxetine will block this transporter, which prevents norepinephrine from leaving. 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, 7].

Animal studies suggest that atomoxetine also blocks dopamine reuptake in the prefrontal cortex. More importantly, it does not affect dopamine levels in the reward center of the brain. For this reason, atomoxetine is far less addictive than many other ADHD medications [8].

Uses of Atomoxetine

1) Improves 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 [9].

Atomoxetine is primarily used 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 [10, 11, 2, 12].

However, atomoxetine is usually not the first ADHD medication that doctors try. First line medications for ADHD are typically methylphenidate (Ritalin) or amphetamine (Adderall). Studies show that the extended-release forms of these drugs are significantly more effective than atomoxetine [10, 2, 13, 14].

Unlike other ADHD medications, atomoxetine is not considered a stimulant. Ritalin, Adderall, and Vyvanse are all stimulants that have an addictive effect. This makes atomoxetine useful when drug abuse and addiction is a concern [9, 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 [15].

A review of 50 clinical studies examined atomoxetine’s role in those with ADHD and an additional mental disorder. Specifically, they looked at anxiety, depression, and substance use disorder. Atomoxetine was still effective in ADHD and did not negatively affect other mental conditions [15].

Research is investigating atomoxetine in other simultaneous disorders including:

  • Autism [16, 17, 18]
  • Bipolar disorder [19]
  • Emotional lability [20, 21]

2) May Improve Addiction

Although the harmful effects of addiction are evident, the cause of addictive behavior is less clear [3].

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 creates a vicious cycle of drug abuse [3].

These impairments are very similar to ADHD symptoms. In fact, ADHD is a strong risk factor for substance abuse in adults [3, 22].

Research is exploring the use of cognitive-enhancing drugs as treatment for substance use disorder [3].

Studies in animals and humans have found that atomoxetine may be helpful in various addictions, including:

According to research, atomoxetine works by reducing impulsive and risk-seeking behaviors. Focus and attention also improved, allowing individuals to better ignore drug-related triggers [32, 33, 24, 29, 30].

There is not enough evidence yet to evaluate atomoxetine’s role in cannabis dependence [34].

3) May Improve Parkinson’s Disease

Parkinson’s disease primarily affects movement, but it can also lead to behavioral and cognitive issues [35].

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 [36].

Norepinephrine may help with the non-movement symptoms of Parkinson’s [36].

An analysis of 7 clinical trials found that atomoxetine improves cognitive function in Parkinson’s disease. Specifically, there were improvements in impulse control and risk-taking behavior [4].

Brain imaging studies also reveal that atomoxetine promotes the growth of connections in the brain [37, 38, 39].

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 [40, 41].

4) May Improve Hoarding Disorder

Compulsive hoarding is a mental disorder that can lead to dangerous living conditions and serious health risks [42].

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 [43].

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 [5].

One clinical trial looked at 12 patients diagnosed with hoarding disorder. They 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 57.2%. The most improved symptoms were inattentiveness and impulse control [5].

5) May Improve 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 study of 12 people, atomoxetine improves movement when combined with physical training. The drug was also safe – it didn’t alter the heart rate or blood pressure [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 found that atomoxetine improves language function. They also found that blood flow to damaged areas of the brain was increased [49].

6) May Improve Seizure Complications

Epilepsy is a brain condition that causes unpredictable seizures to occur. On rare occasions, a person experiencing a seizure may stop breathing, which is called respiratory arrest [50].

The neurotransmitter norepinephrine is known to regulate wakefulness and breathing. Drugs that affect norepinephrine levels may be helpful during breathing complications [51, 52].

A recent mouse study found that atomoxetine reduces respiratory arrest caused by seizures. Interestingly, a moderate dose had the greatest benefit – low and high doses of atomoxetine were less effective [50].

Side Effects

Atomoxetine is generally well tolerated in children and adults. The majority of side effects are mild and few people discontinue therapy due to side effects [2].

Some common side effects include [2]:

  • Headache
  • Stomach pain
  • Decreased appetite
  • Vomiting
  • Sleepiness
  • Nausea

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 appear early, usually within 1 week of starting atomoxetine. Most side effects resolve within 4 weeks [53, 54].

Genetic factors also play a role. Individuals who metabolize atomoxetine slowly can experience more side effects [55].

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 [56].

However, many recent studies have failed to show the same link.

For instance, one review looked at 23 clinical trials which included almost 4k patients. They found no difference between atomoxetine and placebo when it came to suicide [57].

Another immense study examined 280k children who took atomoxetine. Compared to stimulants, atomoxetine was not associated with an increased risk of suicidal events [58].

Several other large studies have found similar results in children and adults. All of this evidence suggests that, at the very least, increased risk of suicide is extremely rare [59, 60].

Heart Effects

Another important area of concern is atomoxetine’s effect on the heart.

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 [61, 62, 59].

Atomoxetine may also negatively impact the QT interval, which is a measurement of the electrical activity of the heart. Based on a study of 41 people, there is a correlation between atomoxetine dose and QT interval. Curiously, this effect was only seen in women. However, other studies have failed to find the same connection [63, 64, 65].

In general, experts report that these heart effects are usually not clinically significant. Certain people at risk for heart issues may benefit from close monitoring [59, 62, 61].

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 [66].

Researchers suggest that atomoxetine should be stopped in patients who show any signs of liver injury [66].

Contraindications

They include [67]:

  • Past 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.

Pregnancy and Breastfeeding Considerations

Atomoxetine was categorized as Pregnancy Category Risk C by the FDA. A 2015 study of almost 1 million pregnancies indicates that atomoxetine may increase the risk of spontaneous abortion. However, this effect may have more to do with ADHD diagnosis rather than the medication.

In general, there are no definitive studies that have shown atomoxetine to be a risk to the fetus. However, caution is always advised if you are going to take the medication while pregnant, and the benefits of taking the medication should be weighed versus any potential risk to the fetus. Please speak to your doctor or a qualified healthcare professional [68].

It is unknown if atomoxetine is found in breastmilk, therefore caution is always advised if you are breastfeeding while taking the medication. Please speak to your doctor or a qualified healthcare professional [69].

Drug Interactions

A wide array of medications can potentially interact with atomoxetine. It’s important to tell your doctor about all the drugs and supplements you are currently taking to prevent interactions.

One important drug interaction is with monoamine oxidase inhibitors (MAOIs), an antidepressant. The FDA has reported serious, sometimes fatal reactions when the two drugs are taken together [70].

The enzyme CYP2D6 is responsible for metabolizing atomoxetine. Other medications that affect CYP2D6, like many common antidepressants, should be avoided. Taking these drugs together can result in dangerously high levels of atomoxetine in the body [1].

Atomoxetine can sometimes increase blood pressure and heart rate. For this reason, atomoxetine should not be taken with other drugs that can affect the heart, such as dopamine and albuterol [61, 63].

Dosage

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 any negative effects, which is an advantage it has over similar medications [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 will 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

At the center of atomoxetine, metabolism is 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].

A slow metabolizer can have drug levels that are 8 times higher than fast metabolizers [1, 71].

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 [55].

Some SNPs associated with CYP2D6 include:

Genetic variations that affect the enzyme COMT are also important. COMT is responsible for inactivating neurotransmitters like dopamine and norepinephrine [72].

Certain SNPs may increase the activity of COMT, leading to reduced dopamine levels and poor cognitive performance [72].

One study of 616 older adults found that variations in rs4680 can increase COMT activity. Researchers found that the GG genotype can affect personality in the elderly. On the other hand, those with an AA genotype may benefit less from dopamine-boosting therapies, being predisposed to lower COMT and higher neurotransmitter levels [73].

Another study shows that rs1344706 is also linked to COMT and may affect the grey matter in the brain [74].

Limitations and Caveats

Atomoxetine is well studied in its treatment of ADHD. However, research into its other uses is much more limited.

While research has shown positive effects on cognition, atomoxetine has not been studied as a nootropic. The safety and effectiveness outside of ADHD patients are unclear.

The natural alternatives for atomoxetine have only been studied in small groups of people. Further investigation is needed to confidently evaluate safety and effectiveness.

Nootropic Effects of Atomoxetine

The term nootropic refers to drugs or substances that can improve brain function in healthy people. Research is currently exploring the cognitive-enhancing effects of many compounds. However, the safety and effectiveness of taking these “smart drugs” is unclear [75].

ADHD medications, like Ritalin and Adderall, have grown popular for their nootropic potential. Research suggests these stimulant drugs improve memory, focus, and motivation [76, 77, 78].

Although atomoxetine is not a stimulant, studies show it does improve cognition as well. These benefits include:

  • Improved attention and focus [2, 24, 23, 79]
  • Improved memory [2, 23, 79]
  • Better impulse control [80, 4, 2, 23]
  • Enhanced visual processing [80]
  • Reduced risk-taking behavior [4, 33]

It is important to note that the cognitive effects of atomoxetine have not been studied in normal, healthy people. All of these benefits were found in patients with mental disorders, primarily ADHD or Parkinson’s.

There are also questions about safety and dosage. The long-term effects of taking atomoxetine in healthy adults are unknown.

As far as dosage goes, research has found that only low doses of stimulants provide a cognitive benefit. It’s unclear if this holds true for atomoxetine, a non-stimulant drug [81].

Natural Alternatives

1) Exercise

It’s no surprise to anyone that exercise is good for the body. However, many people may not realize that exercise can also increase the activity of neurotransmitters in the brain.

Similar to atomoxetine, exercise may increase norepinephrine levels. It also confers benefits to other neurotransmitters, like serotonin and dopamine [82, 83, 84, 85].

One study in rats found that exercise increases norepinephrine levels in the hippocampus, an area of the brain involved in memory. Researchers found an improvement in memory persistence after just one exercise session [86].

A different rat study found that exercise also targets the prefrontal cortex. This results in improvements to attention and focus [87].

Based on a clinical trial of 121 young adults, exercise increases the release of serotonin in the brain. This increase led to improvements in attention and information processing [84].

Research also shows that exercise and serotonin promote the growth of neurons [88, 89, 90].

The dopamine-boosting effect of exercise has many clinical implications as well. Animal studies show an increase in dopamine may improve learning and depression symptoms. One study found that exercise reduces the loss of dopamine neurons, which may help in Parkinson’s disease [85, 91, 92].

2) Amino Acids

Our body creates neurotransmitters by using amino acids as building blocks. We may be able to increase neurotransmitter levels by increasing the amount of amino acids available. Luckily, many of the foods that we eat contain amino acids. Amino acid supplements are also available [93, 94].

Important amino acids include tyrosine and its precursor phenylalanine. Tyrosine is used to create neurotransmitters, such as dopamine and norepinephrine. Our body is unable to make these amino acids. Instead, they are obtained through foods like eggs, meat, and milk [93, 94].

One small study of 12 healthy participants studied the effect of depleting phenylalanine and tyrosine. They found that impulse control was significantly reduced [95].

As an added benefit, tyrosine and phenylalanine may also be helpful in depression and bone strength [96, 97, 98].

Tyrosine itself has many potential health benefits. Research suggests that this amino acid improves cognition during stressful conditions. For example, one study of 22 people found that tyrosine improves working memory during demanding tasks [99, 100].

Other studies show that tyrosine may improve cognition during sleep deprivation, physical training, and exposure to cold [101, 102, 103].

3) Panax Ginseng

Panax ginseng, also known as Asian or Korean red ginseng, may have antioxidant and neuroprotective effects. A compound inside ginseng called ginsenoside increases dopamine and norepinephrine in the brain [104, 105].

In one small study, researchers gave 1,000 mg of ginseng twice a day to 18 children with ADHD. After 2 months, they found that attention and focus significantly improved. A similar study in 33 children also found an improvement in attention and activity [106, 107].

A different study of 16 adults found that ginseng extract improves mental calculation performance [108].

Ginseng may also help in other conditions, such as Alzheimer’s, cancer, and erectile dysfunction [109, 110, 111]

4) Rhodiola Rosea

Rhodiola rosea is a flowering plant that has long been used as a traditional medicine in Eastern Europe and Asia. It is said to have antidepressant, anti-fatigue, and anti-inflammatory properties [112].

The active compounds inside Rhodiola rosea have a variety of biological effects. One important action is the inhibition of the enzyme monoamine oxidase (MAO). This enzyme is responsible for inactivating neurotransmitters. By blocking MAO, this plant can increase neurotransmitter levels in the brain [113].

A review of 9 studies totaling 860 patients found evidence that Rhodiola rosea may help in depression. Most importantly, the plant causes far fewer side effects than antidepressant medications [114].

According to another study of 80 people, Rhodiola rosea may help with stress and mood as well. Participants in the study reported reduced anxiety, stress, anger, confusion, and depression. However, the researchers did not find an improvement in cognitive performance [115].

Other research suggests that Rhodiola rosea may also have potential benefits to memory, fatigue, cancer, and Alzheimer’s [116, 117, 118, 119].

5) Mucuna pruriens

Mucuna pruriens, also known as velvet bean, is a tropical plant used in traditional medicine [120].

High concentrations of the amino acid L-DOPA can be found in velvet bean. L-DOPA is a precursor to dopamine and norepinephrine [121].

This high L-DOPA content makes velvet bean a potential agent in Parkinson’s disease. Currently, the main treatment for Parkinson’s involves using L-DOPA to increase dopamine concentrations in the brain [120].

One recent study of 18 patients compared velvet bean to conventional Parkinson’s medications. Researchers found that velvet bean was just as effective at reducing movement symptoms. The plant was also more tolerable than medication [122].

Velvet bean regulates several components in the immune system including TNF-α, IL-6, and NF-kB. This regulation can help protect neurons from injury and may prevent Parkinson’s progression [123, 124].

Studies suggest velvet bean may also help in diabetes, infections, and snake bites [125, 120, 126].

6) Vitamin B6

The active form of vitamin B6 is called pyridoxal 5’-phosphate, or PLP for short. PLP is used to create neurotransmitters, such as serotonin, dopamine, and norepinephrine [127].

Although vitamin B6 plays a role in neurotransmitter development, it’s somewhat unclear if it can improve cognition. An analysis of two clinical trials found no cognitive benefits in healthy adults [128].

However, other studies suggest that vitamin B6 may protect against cognitive deterioration. For example, one 4 year study revealed that low dietary intake of vitamin B6 is linked to faster cognitive decline. People with low vitamin B6 levels or cognitive impairment may benefit most from supplementation [129, 130, 128].

Low vitamin B6 levels are also linked to other conditions including depression, inflammation, and sleep disturbances [131, 132, 133, 134].

7) Sunlight

Improving brain function may be as simple as going outside more often. There is a strong link between sun exposure and serotonin levels in the brain. Winter months can exacerbate mental disorders, such as depression and anxiety [135, 136].

Regular sun exposure is also important for the creation of vitamin D, nitric oxide, and melatonin. But that’s not all–our circadian clocks depend on proper sun exposure as well [137, 138].

Takeaway

Atomoxetine is primarily used for the treatment of ADHD. Research is exploring its use in addiction, Parkinson’s, and other mental disorders as well.

Atomoxetine can improve attention, impulse control, and cognitive function. This has made it a popular nootropic, although it has not been studied for this purpose.

Natural alternatives like ginseng and Rhodiola may also help with cognition. However, research on these substances is limited.

Although they are rare, atomoxetine comes with certain safety concerns. Evidence suggests there is a small chance it may increase the risk of suicide, heart issues, and liver injury.

Genetic factors can also influence the frequency of side effects as well as drug effectiveness.

About the Author

Mathew Eng, PharmD

PharmD

Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.

Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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