Steph’s Note: Sammie Le is a fourth-year medical student at the Alabama College of Osteopathic Medicine. In her past life, she was a pharmacist (from UT Austin in Texas). You may also remember her from her previous posts on hereditary angioedema and alcohol use disorder. Currently, she is in the middle of residency season and hopes to pursue a psychiatry residency. Her interests include her orange cat (Woody), fountain pens, and mechanical keyboards.

Adderall, Vyvanse, Mydayis, Strattera, Ritalin, Daytrana, Azstarys…feeling overwhelmed? (Me too). Welcome to the world of ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder diagnosed in childhood. It is thought to be caused by a lack of norepinephrine (NE) and dopamine (DA), which leads to impaired executive function, hyperactivity, and impulsivity. ADHD is more common in boys than girls (2:1) and associated with other psychiatric conditions such as anxiety, mood disorders, or substance use disorders. As children progress throughout adolescence, hyperactive/impulsivity symptoms tend to decrease whereas inattention symptoms remain.

ADHD can be categorized into three main subtypes: inattentive-type, hyperactive-type, or mixed. To be diagnosed with ADHD, patients must fulfill the following criteria:

Symptoms must be present/identified before the age of 12.
Symptoms must be present for at least 6 months in 2 or more settings (e.g., school, work), interfere with functioning and/or development, and are not caused by another disorder.
Patients < 16 years require at least six symptoms.
Patients > 17 years require at least five symptoms.

Symptoms are broadly divided into either inattention or hyperactivity/impulsivity. Adults with ADHD typically present with symptoms of inattentiveness (vs hyperactivity/impulsivity).

Pharmacotherapy for ADHD

There are two pharmacologic approaches to ADHD: stimulants and non-stimulants.

Stimulants can either be classified as methylphenidates or amphetamines. These medications inhibit dopamine and norepinephrine reuptake at presynaptic and post-synaptic membranes and improve cortical function.

Amphetamines have a unique mechanism of action in that at high doses, they enter pre-synaptic neurons, displace dopamine from vesicles, and increase dopamine release into the synapse. In general, amphetamines are considered more potent than methylphenidates, which work primarily via dopamine transport inhibition.

Let’s get into the meat of this article – drugs!

Amphetamines for Management of ADHD

Evekeo, Zezendi, Adderall, and Procentra are approved for patients aged 3 and up and have minimal pharmacokinetic interactions. However, amphetamines inhibit monoamine oxidase transporters so be mindful of waiting 2 weeks after stopping an MAOI before starting a stimulant.

Methylphenidates for Management of ADHD

These are approved for patients aged 6 and up and have minimal pharmacokinetic interactions.

In general, stimulants are titrated weekly. It is common to see patients stopping medications throughout the summertime and resuming them once the school year picks back up. You may also see parents who prefer that their children take stimulants during the week, and none on the weekends.

Additionally, we like to stay in one class when combining extended-release and immediate-release medications. For example, you’ll see patients on either IR+ER methylphenidates, or IR+ER amphetamines (vs combining methylphenidate+amphetamine).

Yeahhhh don’t do this… the heart will not appreciate it. (Image)

Although there is not an exact conversion formula, the total daily dose of amphetamine (Adderall) is roughly ½ the methylphenidate dose (Ritalin). Therefore, 10 mg of Adderall is roughly equivalent to 20 mg of Ritalin.

Stimulants have minimal food/drug interactions—however, there are a LOT of formulations, and it is important to remain mindful about which medications can be opened/sprinkled/etc. Side effects of stimulants include loss of appetite, increased HR/BP, headaches, and sleep disturbances. Before initiating a stimulant, be sure to ask about a history of cardiovascular disease, family history of sudden cardiac death, arrhythmias, or hypertrophic cardiomyopathy.

Unfortunately, stimulants have been shown to cause delayed growth in children (which is why we recommend drug holidays).

Non-Stimulants for Management of ADHD

The end is in sight, y’all. Let’s move onto non-stimulants. Nonstimulants have less abuse potential than amphetamines/dexmethylphenidates, but they are not as effective for ADHD. Unfortunately, there have been no head-to-head trials comparing stimulant vs non-stimulant medications for ADHD.

Kapvay and Intuniv have been approved as adjunctive therapy alongside stimulants.

Common things are common…

Is it an amphetamine or methylphenidate? You decide! (Just kidding). Here’s another table of the most common brands that popped up during rotations:

Stimulants versus Non-stimulants: What should I pick?

It’s nice to know aaallll the medications (yay pharmacy!). But how do we actually treat ADHD?

For starters, it’s important to know that pharmacotherapy is most effective when combined with behavioral therapy. According to the treatment guidelines from the American Academy of Pediatrics, stimulants are recommended as first line pharmacotherapy. Responses to methylphenidates/amphetamines are highly patient-dependent and do not vary based on ADHD subtype.

The AAP recommends methylphenidate as first line in preschool children (aged 4 to 6) with moderate/severe ADHD symptoms. In general, we prefer to initiate treatment with a stimulant (methylphenidate or amphetamine). These work quickly but have the disadvantage of having a higher potential for abuse.

Additionally, stimulants increase blood pressure/heart rate (so, not recommended for patients with cardiac abnormalities). Although methylphenidates and amphetamines have been proven to be efficacious for ADHD, a 2017 meta-analysis suggested that children may experience more irritability with amphetamine formulations.

On the other hand, non-stimulants have less abuse potential, but it may take weeks to see the full effect. We can definitely consider starting a non-stimulant if patients have a history of substance use disorder or have contraindications to stimulants (cardiovascular disease, valvular disease, glaucoma, hyperthyroidism, etc).

When considering individual medications, we have to think about our patient. Can our 3 year old patient swallow capsules or tablets? If not, maybe we can consider a chewable tablet or solution.

As always, we have to engage in the ritualistic dance with insurance. What does Medicaid approve? Blue Cross Blue Shield? (Many insurances require that the patient has several medication trials before approving the medication that you want to prescribe).

The tl;dr of ADHD Medications

Phew, that was a lot. To summarize, Attention-Deficit Hyperactivity Disorder (ADHD) can be categorized as inattentive, hyperactive, or mixed. To be diagnosed, symptoms must be present for at least 6 months in two or more settings and be present/identified before the age of 12.

Treatment consists of either stimulants or non-stimulants (or both!) along with behavioral therapy. Methylphenidates are commonly preferred over amphetamines (with caveats)!

The Art of ADHD