What is the first-line medication for a typical adult patient with attention deficit hyperactivity disorder (ADHD)?

First-Line ADHD Medication for Adults

Long-acting stimulant medications—specifically amphetamine-based formulations (such as lisdexamfetamine or mixed amphetamine salts extended-release) or long-acting methylphenidate formulations (such as Concerta)—are the first-line treatment for adult ADHD, with amphetamine-based stimulants preferred based on comparative efficacy studies. 1

Primary Recommendation: Long-Acting Stimulants

Amphetamine-based stimulants are the preferred first-line option for adults with ADHD, achieving 70-80% response rates with the largest effect sizes among all ADHD medications 1, 2. Long-acting formulations are strongly preferred over immediate-release preparations due to:

• Better medication adherence with once-daily dosing 1
• Lower risk of rebound effects and more consistent symptom control throughout the day 1
• Reduced diversion potential and lower abuse risk compared to immediate-release formulations 1
• Around-the-clock coverage extending beyond work hours, addressing functional impairment across multiple settings 1

Specific First-Line Options:

Lisdexamfetamine (Vyvanse) provides once-daily dosing with a prodrug formulation that reduces abuse potential, making it particularly suitable for adults 1. Starting dose is typically 30 mg once daily in the morning, titrating by 10-20 mg weekly up to 70 mg maximum 1.

Mixed amphetamine salts extended-release (Adderall XR) should be started at 10 mg once daily in the morning, titrating by 5 mg weekly up to 50 mg maximum 1, 3.

Methylphenidate long-acting formulations (Concerta) utilize an OROS delivery system resistant to tampering, providing 12-hour coverage 1. The maximum recommended daily dose is 60 mg, with average effective doses of 20-30 mg daily 1, 4.

Dosing Strategy

Start low and titrate systematically to optimal effect rather than relying on strict mg/kg calculations 1. For methylphenidate, response rates reach 78% versus 4% placebo when dosed appropriately at approximately 1 mg/kg total daily dose 1. Stimulants work within hours to days, allowing rapid assessment of ADHD symptom response 3, 5.

If inadequate response occurs after adequate treatment with one stimulant class, trial the other class before considering non-stimulants 1. Approximately 40% of patients respond to both methylphenidate and amphetamine, while 40% respond to only one 1.

Monitoring Requirements

Before initiating treatment, assess for:

• Cardiac disease through careful history, family history of sudden death or ventricular arrhythmia, and physical exam 4
• Substance abuse disorder, as prescribing stimulants to adults with comorbid substance abuse requires particular caution 1
• Family history of tics or Tourette's syndrome 4

Obtain baseline blood pressure, pulse, height, and weight before starting treatment 6. Monitor blood pressure and pulse at each medication adjustment and quarterly during stable treatment 1, 6. Track appetite, sleep disturbances, and weight changes as common adverse effects 1.

Second-Line Non-Stimulant Options

Atomoxetine is the only FDA-approved non-stimulant for adult ADHD, recommended when stimulants are contraindicated, not tolerated, or in patients with active substance abuse disorder 1, 3. Target dose is 60-100 mg daily, but requires 6-12 weeks to achieve full therapeutic effect with median time to response of 3.7 weeks 1, 6. Effect sizes are medium-range (approximately 0.7) compared to stimulants (1.0) 1.

Extended-release guanfacine or clonidine (alpha-2 adrenergic agonists) demonstrate effect sizes around 0.7 and can be used as monotherapy or adjunctive therapy with stimulants 1, 6. Guanfacine dosing is 1-4 mg once daily, requiring 2-4 weeks for full effect 6. Evening administration is preferable due to sedative effects 1, 6.

Critical Contraindications to Stimulants

Avoid stimulants in patients with:

• Uncontrolled hypertension or symptomatic cardiovascular disease 1, 6
• Active substance abuse disorder (unless in controlled setting) 6
• Current use of MAO inhibitors or within 14 days of discontinuation due to risk of hypertensive crisis 4
• Active psychotic disorder 6
• Known hypersensitivity to methylphenidate or amphetamines 4

Common Pitfalls to Avoid

Do not assume the presence of anxiety contraindicates stimulant use—stimulants can directly improve executive function deficits and may indirectly reduce anxiety related to functional impairment 1, 6. Anxiety requires careful monitoring but is not a contraindication 6.

Do not underdose stimulants—many adults require total daily doses of 20-40 mg for amphetamines or up to 60 mg for methylphenidate to achieve optimal symptom control 1, 4. Systematic titration to optimal effect is more important than conservative dosing 1.

Do not discontinue effective ADHD treatment solely due to concerns about long-term medication use—untreated ADHD is associated with increased risk of accidents, substance abuse, criminality, and functional impairment 1. A 7-week randomized discontinuation study demonstrated significant symptom worsening when medication was stopped after more than 2 years of treatment 1.