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According to the US CDC, there was a 40% increase from 2003 to 2019 in the number of children and adolescents in the US with a diagnosis of ADHD, representing 6 million affected individuals, or 9.4% of the US pediatric / adolescent population.

Data show that the frequency of adult ADHD diagnoses has also increased, with prevalence estimates ranging from 1-5% in the US.

Symptoms of ADHD – such as inattentiveness, hyperactivity, and impulsivity – are treated using two main categories of medications: stimulants and nonstimulants.

Stimulants are either methylphenidate or amphetamine-based agents, which differ in important ways.

Methylphenidate works by inhibiting the reuptake of dopamine and norepinephrine in the brain. The availability of these neurotransmitters in the synaptic cleft is increased, which improves attention and impulse control.

Like methylphenidate, amphetamines inhibit dopamine and norepinephrine reuptake, but they also increase the release of these neurotransmitters into the synaptic cleft.

This dual mechanism enhances the potency of amphetamine relative to methylphenidate in ways that impact efficacy, tolerability, and abuse liability.

• Common adverse events with stimulants include:
• Decreased appetite
• Dry mouth
• Gastrointestinal effects
• Anxiety
• Headache
• Insomnia
• Jitteriness
• Moodiness/irritability, and
• Increases in blood pressure and pulse rate

In clinical trials, patients were 2.3-fold more likely to discontinue amphetamine than placebo due to these adverse events, but only 1.44-fold more likely to discontinue methylphenidate compared with placebo.

There are several methylphenidate and amphetamine formulations from which clinicians can choose.

The original racemic methylphenidate formulation contains an active d-threo enantiomer and an inactive I-threo enantiomer.

Methylphenidate is now available in either the racemic form or as dexmethylphenidate, a single-enantiomer formulation.

Dexmethylphenidate includes only the d-threo enantiomer and is considered a cleaner drug that eliminates exposure to the inactive enantiomer, potentially reducing adverse effects.

However, it is also more expensive.

Amphetamine is available as racemic amphetamine, a mixed-salt formulation that includes two active metabolites- dexamphetamine and lisamphetamine, with dexamphetamine enantiomer the more active of the 2.

Dexamphetamine is available as a stand-alone drug for patients who can experience adequate symptom relief without exposure to the less active enantiomer. This can reduce side effects and perhaps abuse potential.

Immediate-release and extended-release formulations are available for each of these amphetamine and methylphenidate medications.

In addition, extended-release lisdexamphetamine, a prodrug of dexamphetamine, is available. Gradual conversion of the inactive prodrug to active dexamphetamine provides more gradual drug release, which can further reduce side effects and abuse potential.

With these short- and long-acting options at their disposal, nurses and other clinicians can tailor therapy for optimal efficacy and tolerability in each patient, while also addressing the potential for abuse.

Long-acting stimulants offer:

• Convenient, simplified dosing once or twice daily
• Reduced stigma for children who may need to take medication at school
• Less burden on schools for medication storage and administration
• Improved treatment adherence
• More time with therapeutic drug concentrations

In addition, insurance claims data indicate that children with ADHD who receive long-acting stimulants have fewer emergency department visits and hospitalizations than children on short-acting stimulants.

Nonetheless, short-acting stimulants:

• May allow for more flexibility with dosing frequency and titration
• They can be taken on an as-needed basis when coverage is only needed a limited number of hours daily

According to AAP guidelines, elementary school-aged children (6-11 years) should receive FDA-approved medications for ADHD, in conjunction with parent training in behavior management and/or a behavioral classroom intervention (preferably both).

No recommendation is given for long-acting vs short-acting stimulants at this age.

For adolescents between the ages of 12 and 18 years, the AAP also recommends prescribing FDA-approved medications, with the adolescent’s assent.

Given added risks associated with driving, long-acting or late-afternoon short-acting stimulants may be preferred.

Adolescents should also receive evidence-based training interventions to improve function in social and academic settings, along with behavioral interventions.

For adult ADHD, guidelines issued by the American Academy of Family Physicians (AAFP) prioritize long-acting stimulants over short-acting stimulants, noting that 70% of adults report satisfaction with a long-acting agent, compared with 40-50% reporting satisfaction with a short-acting stimulant.

When present, comorbid depression should be treated before the ADHD, utilizing cognitive-behavioral therapy and adjunctive antidepressants, if needed.

The AAFP pays particular attention to comorbidities that emerge in adolescence or adulthood and are contraindications for stimulants.

These include cardiovascular risk factors and disease, certain psychiatric comorbidities, and anorexia.