Managing Medications

Stimulant, Non-Stimulant, or Both? Combination Therapy for ADHD

Combining a stimulant with a non-stimulant optimizes ADHD symptom management for some people.

By Greg Mattingly, M.D. Verified Updated on May 21, 2024
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Q: Can a stimulant and a non-stimulant medication be used together to reduce ADHD symptoms?

A study by Tim Wilens, M.D., and colleagues followed children and teens who were treated for ADHD with the non-stimulant medication atomoxetine, a selective norepinephrine reuptake inhibitor (SNRI). The children’s symptoms significantly improved; their ADHD rating scale scores dropped from a 34 to a 21. However, 21 is still quite a high level of symptoms. I want all symptoms on the ADHD rating scale to be mild or minimal, on average, which means achieving a score under 18.

So, the researchers added OROS methylphenidate to the atomoxetine, and the subjects’ ADHD symptoms dropped almost by half to 12. At this point, there was very little functional impairment from the ADHD symptoms: all 18 symptoms were either mild or undetectable. In this study we see demonstrable benefits of combination therapy, adding a stimulant on top of a non-stimulant for optimized management of ADHD symptoms.

Q: When would you consider switching a patient from a stimulant to a non-stimulant for ADHD?

In the following situations:

  • If I suspect someone with ADHD is misusing their stimulant, I’m going to switch to a non-stimulant or a longer-acting preparation with less chance for abuse.
  • If the stimulant is making a patient moody or irritable, or if it significantly impairs sleep or appetite, I’m going to try switching to a non-stimulant.
  • If I’m contending with breakthrough efficacy issues, I’ll layer on the non-stimulant to see how much that helps. Then, if I think I can pull back the stimulant, I may do that and be stimulant-sparing in those patients.

How and when to make the switch depends on the patient. It’s important to note you don’t have to go cold turkey on the stimulant. Quite often, there’s an overlap. Sometimes, I layer on the non-stimulant and give it time to start working.

[Read: ADHD Medication Side Effects No One Should Tolerate]

We know from Wilens’ research that a stimulant added to a non-stimulant can be effective, but questions remained about the efficacy of a non-stimulant added to a stimulant. Some of the atomoxetine research has shown that, if they have already tried a stimulant, a patient is less likely to respond to atomoxetine.

That led some colleagues and I to investigate the efficacy of viloxazine, an SNRI which also has some serotonin effects, in patients who had previously used stimulants. For adults with ADHD who had previously used a stimulant, we saw significant improvement in ADHD symptoms on viloxazine, which is sold under the name brand Qelbree.

We don’t know exactly why patients responded well to the addition of viloxazine; maybe it’s the mechanism of action. Regardless, this is promising, particularly when we’re considering switching patients to a non-stimulant.

[Read: Non-Stimulant ADHD Medication Overview] 

Q: Which patients may benefit from adding an alpha agonist, like clonidine or guanfacine, to a stimulant medication?

For certain patients, adding guanfacine on top of a stimulant can be really beneficial. Specifically, I’ve seen this help patients who have impulse-control issues, people with emotional impulsivity, and people who have a hard time settling down at night.

For my patients with tics, I’ve found that a little bit of an alpha agent plus a little bit of a stimulant is better than either one by itself. The stimulant by itself increases the level of tics, and the alpha agent by itself isn’t quite good enough when it comes to cognitive function. The two of them together, however, are sometimes really beneficial in treating the ADHD and the tics.

Combination Therapy: Next Steps

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