Optimizing ADHD Outcomes With Stimulant and Non-Stimulant Options

While stimulant medications remain first-line therapy for attention-deficit/hyperactivity disorder (ADHD), a growing range of formulations and non-stimulant alternatives has expanded the treatment landscape. In this video, Psych Congress NP Institute Co-Chair Julie Carbray, PhD, PMHNP-BC, PMHCNS-BC, FAAN, explains key differences in stimulant and non-stimulant treatment options for ADHD. Dr Carbray offers practical tips for selecting an initial therapeutic approach, reviews mechanism of action, onset, and side effect considerations, and highlights the role that patient input may play in developing an effective, personalized treatment plan.

• In attention-deficit/hyperactivity disorder (ADHD), stimulant compounds (methylphenidate-based and amphetamine-based) increase synaptic dopamine and norepinephrine to improve focus and frontal cortex function, with amphetamine products also promoting presynaptic norepinephrine release that may confer greater potency.
• Non-stimulants for ADHD enhance norepinephrine, and some also act on serotonergic receptors, potentially offering benefits for irritability, mild mood impairment, executive functioning, and overall functioning with a more favorable side-effect profile and without Schedule II classification.
• The choice between stimulant and non-stimulant therapy should be individualized based on side-effect profiles, onset of action, daily duration needs, functional goals, and shared decision-making aligned with patient lifestyle and treatment preferences.

Julie Carbray, PhD, PMHNP-BC, PMHCNS-BC, FAAN: I'm Julie Carbray. I'm a psychiatric nurse practitioner, and Co-Chair of Psych Congress NP Institute, Psych Congress, and also one of our Steering Committee members. I’m a clinical professor of psychiatry and nursing at the University of Illinois-Chicago’s Institute for Juvenile Research, and the Department of Psychiatry and College of Nursing.

Psych Congress NP Institute: What should advanced practice providers (APPs) understand about the mechanisms of action and pharmacokinetic differences among available stimulant formulations to better individualize care for patients with ADHD?

Carbray: Stimulants have very similar mechanisms of action across different compounds. I think we're now at 32 different types of compounds of stimulants. They're either methylphenidate-based or amphetamine-based. 

Methylphenidate, actually, the mechanism of action is in increasing dopamine and norepinephrine within the synapse, really helping to then help patients with their focus and ability to tune in. Amphetamine-based products have the same mechanism of action, but then an additional action where presynaptically they're actually also releasing more norepinephrine into the synapse as well. It’s almost like a boosted effect. That's why amphetamine products might appear to be a bit stronger or more potent because there's a slightly different mechanism of action. 

But across the board, stimulants really enhance dopamine and norepinephrine to help our patients to focus, to attend, and to be able to implement what they need to do within their frontal cortex. These medications help them to attenuate and to be able to do that more easily. 

Psych Congress NP Institute: When do you consider non-stimulant options, and how can APPs better navigate the growing landscape of alternative treatments for ADHD?

Carbray: While stimulants are often first line and have great efficacy for improving symptoms in ADHD, we also have non-stimulant options, which have become a growing area of investigation. These medications also enhance norepinephrine within the synapse and some of them actually also act on serotonergic receptors, offering an additional benefit in addition to that boost of norepinephrine we see with stimulants. 

These medications also tend to have a better side effect profile. They're more easily obtained and they're not Schedule II like stimulants are. Sometimes that improved side effect profile, the fact that they're more easily obtained, and the potential for also addressing some serotonergic concerns—say if there's irritability or mild mood impairment, or there's even some research looking at executive functioning and improving overall functioning and benefits that might be complementary to stimulants that non-stimulants hold—offer a lot of promise to our patients with ADHD. 

Deciding where you will start with your patient really comes down to potential side effects of stimulant medications versus non-stimulant medications. Stimulants typically act a little faster than do non-stimulants, so we're also looking across the patient's day and what their needs are, how long those days might be, and wanting to have the most symptom control for that patient's daily functioning. So, it really all depends on what the patient presents with. 

I do like to talk with patients about these 2 options at the very outset and have them contribute which seems to make more sense in terms of efficacy and tolerability, their lifestyle, and any obstacles that may be in the way for their continuing forward with this treatment over time.

Julie Carbray, PhD, PMHNP-BC, PMHCNS-BC, APRN, holds her PhD (93) and Master of Science (88) degrees from Rush University, Chicago and her Bachelor of Science (87) degree from Purdue University in West Lafayette, Indiana. A Clinical Professor of Psychiatry and Nursing at the University of Illinois Chicago, she has been practicing as a Psychiatric Nurse Practitioner over 35 years. As the Director of the Pediatric Mood Disorder Clinic, Dr. Carbray leads the clinical program and multidisciplinary training and is a nationally recognized clinical expert in children and adolescents with mood disorders. Dr. Carbray holds a national reputation of excellence in serving families of children with mood disorders, and was recognized with the UIC Preceptor of the year award, the Karen Gousman Excellence in Nursing Award, the American Psychiatric Nurses Association Best Practices in an Outpatient Program for Bipolar Disorder Award, the UIC Inspire Award, the APNA Distinguished Service Award and the Susan McCabe psychopharmacology lectureship from the International Society of Psychiatric Nurses. 

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