Non-Stimulant ADHD Medication Overview
Non-stimulant ADHD medications come in many varieties: FDA-approved non-stimulants, antidepressants, blood pressure medications, and more. These are second-line treatment options for ADHD patients who don’t respond to stimulant medication, or experience too many side effects.
Non-Stimulant ADHD Medication vs Stimulant ADHD Medication
ADHD clinicians prescribe two main types of medication that treat ADHD symptoms:
Stimulant medications are typically the first choice to treat ADHD symptoms because they work for 70-80% of people with attention deficit hyperactivity disorder (ADHD)1. When stimulants don’t work, or patients experience severe side effects, non-stimulant ADHD medication is the most common second-line treatment.
Non-stimulant ADHD medications are considered second-line or third-line treatments because the level of benefits and response rates are significantly lower. Meaning, stimulant medications are more effective at relieving symptoms for a larger percentage of people. Some non-stimulant ADHD medications, like alpha agonists, are often used in addition to stimulant medications.
Unlike stimulants, which are quick-acting, non-stimulant ADHD medications may take a week, or longer, to attain full effectiveness. As a result, it can take much longer to titrate non-stimulant medications — that is, to find the best dosage for maximum symptom control with minimal side effects.
The non-stimulant medication used to treat ADHD fall into two main categories: those approved by the U.S. Food and Drug Administration (FDA) to treat ADHD and those approved by the FDA to treat other conditions, which are used “off-label” to treat ADHD.
FDA-Approved Non-Stimulant ADHD Medication
These non-stimulant ADHD medications are approved by the FDA as safe, proven treatments for ADHD.
Strattera was the first FDA-approved non-stimulant ADHD medication. It is a selective norepinephrine (noradrenaline) reuptake inhibitor (SNRI). Strattera works similarly to selective serotonin reuptake inhibitors (SSRIs) that are used to treat depression by raising levels of the neurotransmitter norepinephrine in the brain. This can help some hallmark symptoms of ADHD: hyperactivity, inattention, and impulsivity.
Strattera is considered a third-line treatment for ADHD by the American Academy of Child and Adolescent Psychiatry (AACAP) because the response rate and effect size to atomoxetine is only approximately 50% that of the stimulant medicines.2 It works for roughly half of the people who take it and has about half of the clinical effect on symptoms and impairment.
The most common side effects of Strattera include decreased appetite, nausea, vomiting, fatigue, dyspepsia (indigestion), dizziness, and mood swings.
Qelbree is a non-stimulant medication containing a serotonin norepinephrine modulating agent approved by the FDA to treat ADHD in patients 6 to 17 years of age. Its active ingredient, viloxazine hydrochloride, was previously marketed as an antidepressant in Europe. It is the most recent non-stimulant ADHD medication to receive FDA approval for use in children since Intuniv was approved in 2009.
The most common side effects of Qelbree include drowsiness, decreased appetite, fatigue, nausea, vomiting, trouble sleeping, and irritability. Qelbree may also increase suicidal thoughts and actions.
Intuniv is a time-release version of the central alpha2A-adrenergic receptor agonist guanfacine. It is taken once daily and is thought to affect receptors in the brain in a way that improves ADHD symptoms such as emotional sensitivity, hyperarousal, and social aggression. It is not a controlled substance and has a low risk of abuse or dependence. It can be used as a monotherapy or as a complementary treatment alongside ADHD stimulant medications in patients aged 6-17.
The response rate to alpha agonist medications is between 55% and 60%. Alpha-adrenergic agonists, like guanfacine, work best when used in addition to stimulant medications.
The most common side effects of Intuniv are sleepiness, dry mouth, tiredness, difficulty sleeping, nausea, stomach pain, dizziness, irritability, slow heart rate, and low blood pressure. Because of the effect on blood pressure, stopping abruptly or skipping weekends is not recommended.
Kapvay is also an extended-release alpha-agonist medication that relaxes blood vessels and reduces blood pressure. It can also trigger the release of norepinephrine in the brain, which, in turn, improves ADHD symptoms. It can be used for pediatric patients aged 6-17 years old. as a monotherapy or as a complementary ADHD treatment alongside stimulant medications.
The response rate to alpha agonist medications is between 55% and 60%. Like Intuniv, Kapvay works best when used in addition to stimulant medications.
The most common side effects of Kapvay are tiredness, cough, runny nose, sneezing, irritability, sore throat, nightmares, change in mood, constipation, increased body temperature, and ear pain.
Because of the effect on blood pressure, like guanfacine, stopping abruptly or skipping weekends is not recommended.
Medications Used Off-Label for ADHD
The following medications sometimes work to increase dopamine and norepinephrine, two neurotransmitters that exist at low levels in the ADHD brain. As a result, some physicians prescribe them “off-label” to treat ADHD symptoms, meaning that while they are FDA-approved to treat other conditions, they are not approved to treat ADHD. They can be a good choice for people with ADHD and depression but are not generally as effective as the stimulants or FDA-approved non-stimulants for ADHD.
Wellbutrin is the most commonly prescribed antidepressant for ADHD. It is a norepinephrine dopamine reuptake inhibitor (NDRI), which slows down the reabsorption of dopamine and norepinephrine after these chemicals are released into the brain. This action makes these neurotransmitters more available to send messages in the brain. Wellbutrin was first approved by the FDA in 1985 to treat depression. Other brand names of bupropion include Aplenzin, Forfivo, and Zyban.
Effexor XR (venlafaxine)
Effexor belongs to a class of antidepressant medications called serotonin-norepinephrine reuptake inhibitor (SNRI). It is sometimes, but not commonly, used to treat ADHD because it increases levels of norepinephrine and serotonin in the brain, improving mood or concentration. One small study found that treatment with Effexor improved ADHD symptoms for adults3. It is not approved for use in children.
The most common side effects of both Wellbutrin and Effexor XR are nausea and vomiting, weight gain, diarrhea, sleepiness, and sexual problems.
Provigil is a wakefulness-promoting medication. Some research has shown improvement in ADHD symptoms for adults taking Provigil when compared to a placebo4. However, there is a lack of substantial evidence that modafinil can effectively improve symptoms of ADHD.
The most common side effects of modafinil are headache, back pain, nausea, nervousness, stuffy nose, diarrhea, feeling anxious, trouble sleeping, dizziness, and upset stomach.
How to Treat ADHD in Children: Next Questions
- What ADHD medications are used to treat children?
- Is ADHD medication right for my child?
- What are common side effects associated with ADHD medication?
- What natural treatments help kids with ADHD?
- How can I find an ADHD specialist near me?
View Article Sources
1 Advokat, Claire, et al. “Attention-deficit hyperactivity disorder (ADHD) stimulant medications as cognitive enhancers.” Frontiers in Neuroscience, 7: 82. 29 May 2013. doi: 10.3389/fnins.2013.00082
2Childress A. A critical appraisal of atomoxetine in the management of ADHD. Ther Clin Risk Manag. 2016;12:27-39
3 Finding, RL, et al. “Venlafaxine in adults with attention-deficit/hyperactivity disorder: an open clinical trial.” The Journal of Clinical Psychiatry, 57(5): 184-189. 01 May 1996. PubMed PMID: 8626348
4 Turner, D. “A review of the use of modafinil for attention-deficit hyperactivity disorder.” Expert Review of Neurotherapeutics, 6(4): 455-68. 6 April 2006. doi: 10.1586/1473718.104.22.1685