6. ADHD Pharmacological Treatments

What is the frontal lobe & its functions?

• Located at the front of the brain behind the forehead
• Responsible for executive functions:

• Organizing

• Planning

• Paying attention

• Making decisions

In people with ADHD, parts of the frontal lobe may mature a few years later.

What is the dosage and use of immediate-release methylphenidate for ADHD?

• Initial dose: 5 mg once or twice daily

• Max dose: 60 mg per day

Why is immediate-release methylphenidate (MPH) given multiple times a day?

• MPH is effective but has a short half-life (t1/2) of about 2 hours.

• To maintain a consistent plasma level, multiple doses are required.

• Therefore, 2 or 3 doses a day are needed.

What are the potential difficulties created by multiple daily doses of medication for ADHD?

• Compliance (patients may forget to take the medication)

• Social stigma (taking medicine at school may be embarrassing)

• School availability (schools may not be willing or able to store and administer medication)

• Potential for drug diversion (misuse of medication)

• In such cases, a single-dose regimen would be preferred.

What are the two components of all MPH modified release preparations and how do they work?

• Immediate release MPH: Mimics the morning dose, acting quickly to help children get organised for school.

• Modified release MPH: Releases MPH after a few hours to mimic the afternoon dose, improving adherence and reducing the need for school-time medication.

Why is it unwise to change from one MPH preparation to another without considering the PK?

Because the PK profiles are very different, and changing the PK can affect the PD (efficacy and safety).

What are common reactions to methylphenidate?

• ↑ BP

• ↑ HR

• ↓ Appetite

• Weight loss

• ↓ Growth

What is atomoxetine & what are its common adverse effects?

• Selective noradrenaline reuptake inhibitor

• Used for ADHD in children ≥6 & adolescents

• Exact mechanism in ADHD unknown

• Common side effects:

  • Abdominal pain, ↓ appetite, nausea, vomiting

  • Early morning awakening, irritability, mood swings

  • ↑ HR & small ↑ BP

  • Higher risk of suicidality (meta-analysis)

What is the dosing & metabolism info for atomoxetine?

• Children/adolescents ≤70 kg:

  • Start: 500 micrograms/kg daily

  • Max: 1.8 mg/kg daily (single or split dose)

• Adolescents >70 kg:

  • Start: 40 mg daily

  • ↑ according to response, usual maintenance: 80 mg

• Metabolised by CYP2D6

  • Slow metabolisers may need dose reduction

What are other effective drugs for ADHD besides methylphenidate & atomoxetine?

• Amphetamines: dextroamphetamine, lisdexamfetamine

• α₂ receptor agonists: guanfacine (licensed), clonidine (not licensed in UK)

What is the hypothesized mode of action of guanfacine in ADHD?

• Acts on the prefrontal cortex (PFC)

• Promotes maturation of dendritic spines

• ↑ Number, density & length of dendritic spines

• Dendritic spines support synaptic transmission linked to learning & memory