Proven alternate choices to stimulant medications include atomoxetine, guanfacine XR, and bupropion. Because they have not been studied as rigorously or used as much as stimulants, most of these medications are considered second-line (second-choice) treatments. Some non-stimulants may be appropriate for children who have been diagnosed with ADHD and certain coexisting conditions—such as ADHD with accompanying tic disorders (such as Tourette disorder)—because they can in some cases treat both conditions simultaneously.
Atomoxetine (Strattera) is a non-stimulant approved by the FDA for the treatment of ADHD. It is in the class of medications known as selective norepinephrine reuptake inhibitors. Because atomoxetine does not seem to have a potential for abuse, it is not classified as a controlled substance. At the same time, because atomoxetine is a newer medication, the evidence supporting its use is more limited than for stimulants. Atomoxetine, unlike stimulants, is active around the clock. However, atomoxetine has been found to be only about two-thirds as effective as stimulant medications. After starting atomoxetine it may take up to 6 weeks before it reaches its maximum effectiveness. Atomoxetine has a warning on it that it may, in a very small number of cases, have some potential for causing suicidal thoughts in the first few weeks of treatment. On the other hand, atomoxetine may be helpful in the treatment of children who have both ADHD and anxiety. Side effects are generally mild but can include decreased appetite, upset stomach, nausea or vomiting, tiredness, problems sleeping, and dizziness. Jaundice is mentioned in a warning on the medication, but is extremely rare. Taking atomoxetine with food can help avoid nausea and stomachaches. Atomoxetine should be used in lower doses in children also taking certain antidepressants like fluoxetine (Prozac) or paroxetine (Paxil), because it can raise the atomoxetine levels in the bloodstream.
Atomoxetine is now considered an option for first-line therapy for ADHD, and is the first non-stimulant to fall into the first-line category. Parents concerned about the possibility that stimulants may be used for substance abuse may choose atomoxetine as the first-line agent for their child. It is often used for children who have had unsuccessful trials of stimulants.
Long-Acting Guanfacine and Other Alpha Agonists
Long-acting guanfacine (Intuniv) is in the group of medications known as alpha agonists. These medications were developed for the treatment of high blood pressure but have also been used to treat children with ADHD who have tics, sleep problems, and/or aggression. It has recently been approved by the FDA for the treatment of children with ADHD. Longacting guanfacine is a pill, but it cannot be crushed, chewed, or broken and must be swallowed whole. Like atomoxetine, it is not a controlled substance. It does not cause much appetite suppression, so may be a good choice for children who lost a significant amount of weight when taking a stimulant. Side effects can include sleepiness, headaches, fatigue, stomachaches, nausea, lethargy, dizziness, irritability, decreased blood pressure, and decreased appetite. Although sleepiness occurs in a large number of children when children start taking long-acting guanfacine, it seems to get better as they continue to take it. It may take 3 to 4 weeks to see medication benefit. Two other shorter-acting alpha agonists are available for use, but not approved by the FDA for ADHD. These are clonidine (Catapres) and short-acting guanfacine (Tenex). These can be used as adjunctive medications, or if FDA-approved medications are not helpful. If no FDA-approved medication has been found helpful for your child, you should also consider whether ADHD is the correct diagnosis, and whether additional coexisting conditions might be present. The alpha agonists can be used to treat tics, and because about half of children who have a tic disorder called Tourette disorder also have ADHD, they may be useful in this context.
Bupropion is a unique type of antidepressant that has been less frequently studied as a treatment for ADHD. It is also not FDA approved for ADHD. Some research that has been done indicates that bupropion is effective in reducing ADHD symptoms in some children, but it seems to have less effect than stimulants or atomoxetine. Its use in ADHD is not widespread. The side effects, though usually minimal, can include irritability, decreased appetite, insomnia, and a worsening of existing tics. It is important to note that at higher doses, bupropion may make some individuals more prone to seizures, so it should be used cautiously in children who have seizure disorders.
Non-Stimulant Medications Used for ADHD
| Once a day to twice a day
||0.5 mg/kg per day|
1.4 mg/kg per day)
|1–4 mg daily
1–2 mg 2 to 3 times daily
|Start at lower doses|
|0.1–0.3 mg 2 to 3 times daily
0.1–0.3 mg patch daily
|Start at lower doses|