The 3 types of non-stimulant ADHD medications and how they work
- Non-stimulant medications approved by the FDA for ADHD are Atomoxetine, Clonidine, and Guanfacine.
- Non-stimulant medications are used if someone does not respond to stimulant medication, has a history of drug abuse, or experiences severe side effects from stimulants.
- Other medications, like antiviral drugs and antidepressants, also do not have any stimulant effects and may be used to treat ADHD.
- This article was reviewed by Jason R. McKnight, MD, MS, a family medicine physician and clinical assistant professor at Texas A&M College of Medicine.
There are two main types of medication for ADHD — stimulants, and non-stimulants:
- Stimulants are the first-line of treatment for people with ADHD and include medications like Adderall and Vyvanse.
- Non-stimulants are often prescribed when a person either shows no response to stimulant medication, has a history of drug abuse, or experiences severe side effects from stimulant medication.
Here are the types of non-stimulant medications, how they work, and some common side effects.
Why opt for non-stimulants?
Stimulants are usually the first line of treatment for ADHD, but as of the early 2000s, research shows that an estimated 30% to 50% of treated children and adults discontinue stimulant medication due to adverse effects or inadequate response.
"While stimulants are stronger and work better, they are more likely to cause addiction and side effects. Non-stimulant medications, on the other hand, are not as potent but are less likely to cause side effects and don't have any addiction potential," says Ravi N. Shah, MD an Assistant Professor of Psychiatry at Columbia University Irving Medical Center.
Moreover, stimulants and non-stimulants affect the brain differently. Stimulants work by increasing the production of dopamine and norepinephrine in the brain. These chemicals help people with ADHD to maintain focus and reduce symptoms of hyperactivity and impulsivity.
"Unlike stimulant medication which increases the amount of neurotransmitters like dopamine in the brain, non-stimulants like Atomoxetime keep the already existing receptors fired for longer. It's a subtle difference, but the important thing to note is that this makes Atomoxetine less likely to be addictive," says Shah.
There are currently three non-stimulant ADHD medications that the FDA has approved for adults and children: atomoxetine, clonidine, and guanfacine.
Atomoxetine
Atomoxetine, which is usually marketed under the brand name Strattera, was the first non-stimulant ADHD medication to be approved by the FDA in 2002.
It isn't clear how atomoxetine works to limit ADHD symptoms. However, researchers believe that it inhibits the reabsorption of norepinephrine, a neurotransmitter that boosts focus. This leads to an increase of norepinephrine in the brain and helps to control the main symptoms of ADHD.
A cumulative review of 50 clinical studies that examined the efficacy of atomoxetine showed that it is effective in treating ADHD symptoms in both children and adults. However, it is not as efficient as stimulants.
According to the American Academy of Child and Adolescent Psychiatry (AACAP), the response rate to atomoxetine is only about 50%. And some side effects caused by the use of atomoxetine include fatigue, indigestion, and mood swings.
Atomoxetine is usually given once or twice a day. Adults are started at an initial dose of 40 mg a day. The dosage for children is usually determined by their weight. Children who weigh below 70 kg are started at an initial dosage of 0.5 mg multiplied by their weight in kilograms. While children who weigh above 70 kg are started at an initial dose of 40 mg.
Clonidine
Clonidine was originally developed to treat high blood pressure but was found to also be effective in helping people with ADHD manage their symptoms.
The exact way Clonidine helps to improve ADHD symptoms is unclear. However, it has been shown to improve symptoms of inattention, impulsivity, and hyperactivity in people with ADHD by stimulating the area of the brain responsible for attention and impulse control.
Clonidine is available in two formulations:
- Immediate-release: Catapres is the brand name for the immediate-release formulation of Clonidine. When used for ADHD, it is usually started at a low dose of about 0.05 – 0.1 mg daily and a maximum dose of 0.4 mg daily.
- Extended-release: Kapvay is the brand name for the extended-release formulation and is approved by the FDA for children and teenagers between the ages of 6 and 17.
One of the disadvantages of Clonidine is its sedative effects. Other common side effects include low blood pressure, fatigue, nausea, and vomiting. If you already have a history of low blood pressure, Clonidine might not be the best option.
Guanfacine
Guanfacine, like Clonidine, was also originally developed to lower high blood pressure. It works by activating postsynaptic norepinephrine receptors and strengthening the brain's prefrontal cortex. This part of the brain is responsible for complex behavior, decision making and moderating social behavior. Improved function in this part of the brain helps with regulation of attention and impulse control in people with ADHD.
A study published in 2012 in the Journal of Child and Adolescent Psychopharmacology looked at 631 subjects aged 6-17 with ADHD. The researchers found that, after 3-5 weeks of treatment, Guanfacine was significantly more effective than a placebo for treating symptoms of inattention, hyperactivity, and impulsivity in ADHD.
Guanfacine is currently only approved for children and teenagers who are between the ages of 6 and 17. It is also available in two formulations:
- Immediate-release: This is usually prescribed to be taken up to twice a day in 1 mg or 2 mg doses and is marketed under the brand name Tenex. This formulation of Guanfacine isn't prescribed to children under the age of 12.
- Extended-release: This is marketed under the brand name Intuniv. It is usually prescribed to be taken once a day in 1 mg, 2 mg, 3 mg or 4 mg doses.
Some side effects that may occur when taking Guanfacine are nausea, tiredness, low blood pressure, and headaches.
Other ADHD medications
Other types of non-stimulant ADHD medication that a doctor may prescribe include:
- Antiviral drugs like Symmetrel stimulate the production of dopamine and can help with ADHD symptoms. Dopamine is associated with the brain's pleasure and reward system. It also regulates motivation. As a result, a boost in dopamine production may improve attention in activities that won't usually hold the attention of people with ADHD.
- Antidepressants such as Wellbutrin work by slowing down the reabsorption of dopamine and norepinephrine after these chemicals have been released into the brain. Some studies have shown that this might help improve concentration and focus in people with ADHD.
Note that these medications are FDA approved for other conditions but not ADHD.
The bottom line
Non-stimulant ADHD medications are an effective second-line treatment, especially for people who have trouble with stimulants. Choosing which medication to use ultimately comes down to your individual needs.
"Guidelines suggest that you start with stimulants, but there is a role for non-stimulants in specific situations," says Shah. "For example, for people who have a history of addiction or side effects on stimulants. There are also many people who just do not like the idea of taking a medicine that is a controlled substance, and non-stimulants are a good choice in this scenario as well."