What are the initial pharmacology interventions for Attention Deficit Hyperactivity Disorder (ADHD)?

Initial Pharmacological Interventions for ADHD

Stimulant medications (methylphenidate and amphetamines) are the first-line pharmacological treatment for ADHD due to their superior efficacy, rapid onset of action, and extensive evidence base. 1

First-Line Treatment Options

• Methylphenidate (MPH) formulations are the most commonly prescribed first-line medications for ADHD across multiple countries and guidelines 2
• Available formulations include immediate-release (IR), extended-release (ER), and osmotic-release oral system (OROS) methylphenidate 2
• Amphetamine formulations (including lisdexamfetamine) are also considered first-line options with similar efficacy to methylphenidate 1
• For patients with severe ADHD symptoms and no contraindications to stimulants, stimulant medications should be used first 2

Dosing Recommendations for First-Line Treatments

• For children and adolescents up to 70 kg: Start methylphenidate at lower doses (approximately 5-10 mg/day) and titrate gradually while monitoring side effects and improvement 2
• For children and adolescents over 70 kg and adults: Initiate treatment at 40 mg/day for atomoxetine or appropriate doses of methylphenidate based on formulation 3
• Maximum recommended doses vary by medication and country guidelines:
  • Methylphenidate: 60-72 mg/day (depending on formulation) 2
  • Atomoxetine: 100 mg/day or 1.4-1.8 mg/kg/day 2, 3

Second-Line Treatment Options

• Atomoxetine (a norepinephrine reuptake inhibitor) is the primary second-line treatment when stimulants are ineffective or poorly tolerated 1, 3
• Alpha-2 adrenergic agonists (clonidine, guanfacine) are established non-stimulant options with evidence supporting their efficacy 1
• These medications provide "around-the-clock" effects but have smaller effect sizes compared to stimulants 2

Treatment Algorithm

1. First-line: Start with FDA-approved stimulant medications (methylphenidate or amphetamine formulations) 1
2. If first stimulant is ineffective or poorly tolerated: Try an alternative stimulant medication or formulation 2, 1
3. If stimulants are contraindicated or unsuccessful: Switch to atomoxetine 1, 3
4. Alternative non-stimulants: Consider alpha-2 agonists (guanfacine, clonidine) if other options fail 2, 1

Important Considerations for Medication Selection

• Non-stimulants have a slower onset of action:
  • Atomoxetine: 6-12 weeks until full effects are observed 2
  • Alpha-2 agonists: 2-4 weeks until effects are observed 2
• Stimulants have a rapid onset of treatment effects but may cause rebound symptoms when effects wear off 2
• Common side effects of stimulants include sleep disturbances, decreased appetite, and cardiovascular effects (increased blood pressure and pulse) 2, 4
• Common side effects of atomoxetine include decreased appetite, headache, and stomach pain 2, 3

Special Populations and Considerations

• For patients with comorbid substance use disorders, tics/Tourette's disorder, or sleep disorders, non-stimulants may be preferred as first-line options 2
• In patients with hepatic impairment, atomoxetine dosage should be reduced (50% reduction for moderate impairment, 75% reduction for severe impairment) 3
• For patients taking strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) or who are CYP2D6 poor metabolizers, atomoxetine dosing should be adjusted 3

Monitoring and Follow-up

• Monitor vital signs (blood pressure, pulse) regularly, especially with stimulant medications 2, 4
• Assess for gastrointestinal side effects, which are more common with stimulants compared to placebo 5
• Evaluate effectiveness based on reduction in core ADHD symptoms and improvement in functioning 2
• Periodically reassess the need for continued medication treatment 3