What Are the Latest Nonstimulant Treatment Options for ADHD?

What you need to know

• Several new nonstimulant medications for ADHD are in development that work differently than current options
• These new treatments may help patients who don’t respond well to or can’t take stimulants
• Some emerging medications may have benefits for common ADHD comorbidities like anxiety and depression
• More nonstimulant options could allow for more personalized ADHD treatment approaches

The need for more ADHD treatment options

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that causes problems with focus, hyperactivity, and impulsive behavior. While stimulant medications like methylphenidate and amphetamines are effective for many people with ADHD, they don’t work for everyone. About 25-30% of patients don’t get enough symptom relief from stimulants or have troublesome side effects.

Stimulants also aren’t ideal for some patients with conditions like anxiety, depression, or tics that can be worsened by stimulant effects. There are concerns about the potential for non-medical use or abuse of stimulants as well. For these reasons, having more non-stimulant medication options is important for optimal ADHD care.

Currently, there are only three non-stimulant medications approved by the FDA specifically for ADHD:

• Atomoxetine (Strattera)
• Extended-release guanfacine (Intuniv)
• Extended-release clonidine (Kapvay)

While these can be helpful for some patients, they have limitations in terms of effectiveness, side effects, and onset of action. Researchers are working on developing new types of non-stimulant ADHD medications that work in different ways in the brain. Several of these novel treatments have shown promise in clinical trials.

How current non-stimulant ADHD medications work

The existing non-stimulant options for ADHD primarily affect the brain chemical norepinephrine:

Atomoxetine works by blocking the reuptake of norepinephrine, allowing more to be available in the brain. It can be effective but often takes 4-6 weeks to start working. About 45% of patients have a good response, while 40% are non-responders. Common side effects include nausea, decreased appetite, and fatigue.

Guanfacine and clonidine are alpha-2 adrenergic agonists that stimulate norepinephrine receptors in the brain. They can help reduce hyperactivity and impulsiveness. Side effects like drowsiness are common, especially when used alone rather than with a stimulant.

While helpful for some patients, these medications don’t address other brain chemicals involved in ADHD like dopamine and serotonin. The new non-stimulants in development aim to have broader effects.

New types of non-stimulant ADHD medications

Researchers are working on several new categories of medications for ADHD:

Monoamine reuptake inhibitors

These medications block the reuptake of multiple brain chemicals or neurotransmitters involved in ADHD symptoms. Examples in development include:

Dasotraline: Blocks reuptake of dopamine and norepinephrine. Showed benefits for ADHD symptoms in clinical trials but was not approved by the FDA due to side effect concerns.

Centanafadine: Blocks reuptake of norepinephrine, dopamine, and serotonin. Early studies show promise for ADHD symptom improvement.

Receptor modulators

These medications affect specific receptors in the brain rather than broadly increasing neurotransmitter levels. While guanfacine and clonidine fall in this category, researchers are exploring modulators of other receptors like serotonin and histamine for ADHD.

Multimodal agents

This new category combines neurotransmitter reuptake inhibition with direct effects on brain receptors. Examples include:

Vortioxetine: An antidepressant that affects serotonin reuptake and receptors. It showed some benefits for ADHD in an early trial.

Viloxazine: A repurposed antidepressant that affects norepinephrine reuptake and serotonin receptors. It has shown significant benefits for ADHD symptoms in late-stage clinical trials.

Potential advantages of new non-stimulant options

These emerging ADHD medications may offer several potential benefits:

Faster onset of action: Many start working within 1-2 weeks, compared to 4-6 weeks for atomoxetine.

Different side effect profiles: New options may avoid some common side effects of current medications.

Benefits for comorbidities: Some may help with conditions that often occur along with ADHD like anxiety and depression.

Lower abuse potential: Unlike stimulants, these medications are not likely to be misused recreationally.

24-hour symptom coverage: Long-acting formulations may control symptoms throughout the day and evening.

Viloxazine: A promising new option

Of the medications in development, viloxazine is the furthest along in clinical trials. Some key points about viloxazine:

• It affects both norepinephrine and serotonin systems in the brain
• Significant improvements in ADHD symptoms were seen within 1 week in clinical trials
• It was effective for both inattention and hyperactivity/impulsivity symptoms
• Common side effects included sleepiness, headache, and decreased appetite
• Unlike some ADHD medications, it did not appear to negatively impact heart rate or blood pressure

Viloxazine is currently being reviewed by the FDA for potential approval to treat ADHD in children and adolescents. If approved, it would be the first novel non-stimulant ADHD medication in over a decade.

Conclusions

• New non-stimulant ADHD medications with different mechanisms of action are showing promise in clinical trials
• These emerging treatments may help patients who don’t respond well to or can’t take current ADHD medications
• Having more non-stimulant options could allow doctors to better tailor treatment to each patient’s needs
• Some new medications may offer added benefits for common ADHD comorbidities like anxiety and depression
• While stimulants remain effective first-line treatments for many, expanding non-stimulant options is an important goal in ADHD care

The development of new types of non-stimulant medications for ADHD is an exciting area of research. These novel treatments have the potential to expand options for patients and allow for more personalized approaches to managing ADHD symptoms. While more studies are still needed, several promising medications may become available in the coming years to help improve care for people with ADHD.