What is the best medication for an adult with attention‑deficit/hyperactivity disorder (ADHD)?

Best Medication for Adult ADHD

Stimulant medications—specifically methylphenidate or amphetamine-based agents (mixed amphetamine salts, lisdexamfetamine)—are the first-line pharmacologic treatment for adult ADHD, achieving 70–80% response rates with the largest effect sizes (≈1.0) among all ADHD medications. 1, 2

First-Line Stimulant Options

Amphetamine-based stimulants are preferred for adults based on comparative efficacy studies, with methylphenidate serving as an equally effective alternative. 1, 2

Amphetamine Formulations

• Mixed amphetamine salts (Adderall XR): Start at 10 mg once daily in the morning, titrate by 5 mg weekly up to a maximum of 50 mg daily (therapeutic range 10–50 mg/day). 1, 3
• Lisdexamfetamine (Vyvanse): Start at 20–30 mg once daily in the morning, increase by 10–20 mg weekly up to a maximum of 70 mg daily. 1, 2
• Lisdexamfetamine provides once-daily dosing with a prodrug formulation that reduces abuse potential compared to immediate-release preparations. 2

Methylphenidate Formulations

• Dosing: 5–20 mg three times daily for immediate-release, or use extended-release formulations for once-daily dosing with a maximum daily dose of 60 mg. 1
• Extended-release methylphenidate (Concerta): Start at 18 mg once daily, increase by 18 mg weekly up to 54–72 mg daily maximum. 1, 2
• Long-acting formulations are strongly preferred due to better medication adherence, lower risk of rebound effects, more consistent symptom control throughout the day, and reduced diversion potential. 1, 2

Stimulant Efficacy

• Stimulants produce therapeutic effects within days, allowing rapid assessment of ADHD symptom response. 1, 3
• Response rates of 70–80% when properly titrated, with the most robust evidence base from over 161 randomized controlled trials. 1, 2
• Approximately 40% of patients respond to both methylphenidate and amphetamine classes, while another 40% respond to only one class—if inadequate response occurs after adequate treatment with one stimulant class, trial the other class before considering non-stimulants. 1, 2

Second-Line Non-Stimulant Options

Non-stimulant medications are reserved for patients who have failed ≥2 stimulant trials, experience intolerable stimulant side effects, or have an active substance-use disorder. 1, 2

Atomoxetine (Strattera)

• The only FDA-approved non-stimulant for adult ADHD, with a target dose of 60–100 mg daily (maximum 1.4 mg/kg/day or 100 mg, whichever is lower). 1, 2, 4
• Requires 6–12 weeks to achieve full therapeutic effect (median ≈3.7 weeks), significantly longer than stimulants which work within days. 1, 2
• Medium-range effect size of approximately 0.7 compared to stimulants (≈1.0). 1, 2
• Provides 24-hour symptom coverage as a non-controlled substance with no abuse potential, making it particularly useful when substance-misuse risk exists. 1, 2
• FDA black-box warning for suicidal ideation—requires baseline and regular screening for suicidality and clinical worsening, particularly during the first few months or at dose changes. 1, 2

Alpha-2 Adrenergic Agonists

• Extended-release guanfacine (Intuniv) and extended-release clonidine (Kapvay) demonstrate effect sizes around 0.7. 1, 2
• Dosing: Guanfacine 1–4 mg daily; start at 1 mg nightly and titrate by 1 mg weekly. 1
• Full clinical effect observed within 2–4 weeks. 1, 2
• Particularly advantageous for patients with comorbid sleep disturbances, anxiety, tics, or disruptive behavior disorders. 1, 2
• Evening dosing is preferred due to sedative properties (somnolence/fatigue as common adverse effects). 1

Bupropion

• Positioned as a second-line agent for ADHD, to be considered when two or more stimulants have failed or caused intolerable side effects, or when active substance abuse disorder is present. 1
• Low-quality evidence shows bupropion decreased ADHD symptom severity with a standardized mean difference of -0.50, but effect size (≈0.7) is smaller than stimulants. 1
• More rapid onset than atomoxetine but slower than stimulants. 1
• May be particularly useful when comorbid depression is present, though no single antidepressant is proven to effectively treat both ADHD and depression. 1

Viloxazine Extended-Release (Qelbree)

• A repurposed antidepressant classified as a serotonin-norepinephrine modulating agent that has completed several pivotal clinical trials in children showing favorable efficacy and tolerability. 1
• Has demonstrated efficacy in adults with ADHD, though adult data remain limited. 1, 2

Monitoring Requirements

Baseline Assessment

• Measure blood pressure and pulse before starting any ADHD medication. 1, 2, 3
• Obtain detailed personal and family cardiac history, specifically screening for sudden death in family members, cardiovascular symptoms, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, and long QT syndrome. 1
• Screen for comorbid depression, anxiety, bipolar disorder, and substance-use disorders using validated tools. 2

During Titration (First 4–6 Weeks)

• Conduct weekly measurements of blood pressure and pulse. 2, 3
• Obtain weekly ADHD symptom ratings using standardized scales. 1, 2
• Monitor sleep quality, appetite changes, and weight. 1, 2, 3

Maintenance Phase

• Schedule visits monthly initially, then quarterly once stable. 2
• Continue monitoring blood pressure and pulse at each visit. 1, 2, 3
• Track height and weight periodically. 2

Contraindications and Safety Considerations

Absolute Contraindications

• MAO inhibitors: Never combine stimulants, atomoxetine, or bupropion with MAOIs due to risk of hypertensive crisis—at least 14 days must elapse between discontinuation of an MAOI and initiation of ADHD medication. 1, 3
• Active psychosis or mania. 1
• Symptomatic cardiovascular disease or uncontrolled hypertension. 1, 2
• Prior hypersensitivity to stimulants. 1

Relative Contraindications

• History of substance-use disorder: Exercise caution; consider long-acting formulations with lower abuse potential (e.g., Concerta, lisdexamfetamine) or non-stimulants (atomoxetine, guanfacine). 1, 2
• Comorbid anxiety: Recent data indicate stimulants do not necessarily exacerbate anxiety and may improve comorbid anxiety symptoms—the MTA study showed response rates were actually higher in patients with comorbid anxiety. 1, 3
• Comorbid bipolar disorder: Mood stabilizers must be established and optimized before introducing stimulant medications to minimize risk of manic episodes. 1

Common Adverse Effects

• Stimulants: Decreased appetite, insomnia, headache, modest increases in blood pressure (1–4 mm Hg) and pulse (1–2 bpm), weight loss. 1, 2
• Atomoxetine: Somnolence, fatigue, nausea, decreased appetite—adverse effects are less frequent and less pronounced compared to alpha-2 agonists. 1, 2
• Alpha-2 agonists: Somnolence, fatigue, sedation, decreased blood pressure and heart rate. 1, 2
• Bupropion: Headache, insomnia, anxiety, increased seizure risk at higher doses. 1

Treatment Algorithm

1. Initiate a long-acting stimulant (methylphenidate or amphetamine-based) as first-line therapy. 1, 2, 3
2. Titrate systematically by increasing dose weekly until symptoms are controlled or maximum dose is reached (70–80% achieve optimal response with proper titration). 1, 2
3. If inadequate response after adequate trial of first stimulant class, switch to the other stimulant class (40% respond preferentially to one class). 1, 2
4. If both stimulant classes fail or are contraindicated, trial atomoxetine (allowing 6–12 weeks for full effect). 1, 2
5. If atomoxetine insufficient, consider extended-release guanfacine or clonidine (allowing 2–4 weeks for treatment effects). 1, 2
6. Combine pharmacotherapy with evidence-based psychosocial interventions (e.g., CBT, psychoeducation) to achieve optimal functional outcomes. 1, 2

Critical Pitfalls to Avoid

• Do not assume anxiety is a contraindication to stimulant use—this outdated belief deprives patients of the most effective ADHD treatment. 3
• Do not prescribe immediate-release methylphenidate for "as-needed" use—ADHD requires consistent daily symptom control; sporadic dosing fundamentally misunderstands ADHD pathophysiology. 2
• Do not rely solely on weight-adjusted (mg/kg) dosing—systematic titration to the lowest effective dose that yields clinical benefit is preferred. 1, 2
• Do not switch to non-stimulants before completing adequate trials of both stimulant classes at maximum tolerated doses. 1, 2
• Do not discontinue effective ADHD treatment solely due to concerns about "taking medication forever"—untreated ADHD is associated with increased risk of accidents, substance abuse, criminality, and functional impairment. 2