What is the recommended approach to diagnose and manage adult attention‑deficit/hyperactivity disorder, including first‑line stimulant dosing (immediate‑release methylphenidate and mixed amphetamine salts), contraindications such as uncontrolled hypertension, significant cardiac disease, or substance use disorder, monitoring of blood pressure, heart rate, weight, sleep, mood and baseline electrocardiogram if cardiac risk, non‑stimulant options (atomoxetine, extended‑release guanfacine), psychosocial interventions, lifestyle measures, and follow‑up schedule?

Adult ADHD Management

First-Line Pharmacologic Treatment

Stimulant medications—specifically immediate-release methylphenidate (starting 5 mg three times daily, titrating to 5–20 mg three times daily) or mixed amphetamine salts (starting 10 mg once daily, titrating by 5–10 mg weekly to 10–50 mg total daily dose)—are the gold standard for adult ADHD, achieving 70–80% response rates with rapid onset (within days) and the largest effect sizes (≈1.0) of any ADHD medication class. 1, 2

Stimulant Dosing Protocols

Immediate-release methylphenidate:

• Start 5 mg three times daily (morning, midday, early afternoon) 1
• Titrate by 5–10 mg weekly based on symptom control 1
• Typical therapeutic range: 5–20 mg three times daily (maximum 60 mg/day) 1, 2
• Effects appear within days, allowing rapid efficacy assessment 1

Mixed amphetamine salts (Adderall):

• Start 10 mg once daily in the morning 1
• Increase by 5–10 mg weekly 1
• Typical therapeutic range: 10–50 mg total daily dose 1
• Maximum dose generally 40 mg/day, though up to 0.9 mg/kg or 65 mg may be used when lower doses fail and no dose-limiting side effects occur 1

Lisdexamfetamine (Vyvanse):

• Start 20–30 mg once daily 1, 3
• Titrate by 10–20 mg weekly 1
• Therapeutic range: 30–70 mg/day (maximum 70 mg/day) 1, 3
• Prodrug formulation reduces abuse potential compared to immediate-release stimulants 1

Long-Acting Formulations

Long-acting stimulants are strongly preferred over immediate-release preparations because they improve medication adherence, provide consistent all-day symptom control, reduce rebound effects, and lower diversion/abuse potential. 1, 2

Extended-release methylphenidate (Concerta):

• Start 18 mg once daily in the morning 2
• Increase by 18 mg weekly 2
• Typical range: 36–54 mg/day (maximum 72 mg/day in adults) 2
• OROS delivery system provides 12-hour coverage with ascending plasma levels 1

Baseline Assessment Before Initiating Stimulants

Before prescribing any stimulant, obtain: 1, 2

Cardiovascular screening:

• Detailed personal cardiac history: syncope, chest pain, palpitations, exercise intolerance, unexplained seizures 1, 2
• Family history: sudden cardiac death <age 50, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, Long QT syndrome, arrhythmias 1, 2
• Baseline blood pressure and pulse (seated and standing if orthostatic symptoms present) 1, 2, 4
• Height and weight 1, 2

Psychiatric screening:

• Screen for comorbid depression, anxiety, bipolar disorder, psychosis, and substance use disorders using validated tools 1, 2
• Assess family history of bipolar disorder before initiating stimulants 1
• Document prior ADHD treatments: medications, doses, duration, response, side effects, adherence 1

No routine laboratory work or ECG is required unless clinically indicated by history or physical examination. 2 The American Academy of Pediatrics explicitly opposes routine ECG screening before stimulant initiation. 4

Absolute Contraindications to Stimulants

Do not prescribe stimulants in patients with: 1, 2, 3

• Concurrent MAO inhibitor use or within 14 days of MAO inhibitor discontinuation (risk of hypertensive crisis) 1, 2
• Active psychotic disorder 1, 2
• Symptomatic cardiovascular disease (e.g., symptomatic coronary artery disease, serious arrhythmias, structural cardiac abnormalities, cardiomyopathy) 1, 3
• Uncontrolled hypertension (blood pressure must be <130/80 mmHg before initiating stimulants) 2, 4
• Known hypersensitivity to amphetamine or methylphenidate products 1, 3
• Glaucoma 2
• Hyperthyroidism 2

Relative Contraindications Requiring Caution

Substance use disorder:

• Stimulants should be used with great caution in patients with active or recent substance use disorder 1, 2
• Consider long-acting formulations (lisdexamfetamine, extended-release methylphenidate) that have lower abuse potential 1
• Alternatively, use non-stimulant options (atomoxetine, guanfacine, clonidine) as first-line 1, 2
• Implement urine drug screening, controlled substance agreements, and monthly follow-up 1, 5

Controlled hypertension:

• Confirm blood pressure is well-controlled (<130/80 mmHg) before starting stimulants 4
• Monitor blood pressure and pulse at each visit during titration and quarterly during maintenance 1, 2, 4
• If blood pressure rises above target, optimize antihypertensive therapy (add ACE inhibitor, ARB, or calcium channel blocker) rather than immediately discontinuing the stimulant 4
• Consider non-stimulant alternatives (atomoxetine, guanfacine, clonidine) if blood pressure remains difficult to control 4

Seizure disorder:

• Ensure seizures are controlled on anticonvulsant therapy before initiating stimulants 1

Unstable mood disorder:

• Stabilize mood first with mood stabilizers before starting stimulants in patients with confirmed bipolar disorder 1
• However, depression or anxiety alone is not a contraindication to stimulant therapy; both conditions can be managed concurrently 1, 2

Monitoring During Stimulant Therapy

Titration phase (first 4–6 weeks):

• Weekly symptom ratings using standardized scales (patient and informant reports) 1, 2
• Blood pressure and pulse at each dose adjustment 1, 2, 4
• Sleep quality and appetite changes 1, 2
• Weight monitoring 1, 2

Maintenance phase:

• Monthly visits initially, then quarterly once stable 1, 2
• Blood pressure and pulse at each visit 1, 2, 4
• Height and weight tracking (especially in younger adults) 1, 2
• Assess for signs of misuse, diversion, or tolerance 1, 3

Second-Line Non-Stimulant Medications

Non-stimulants are reserved for patients who: 1, 2

• Have failed or cannot tolerate two or more stimulant trials
• Have active substance use disorder
• Have uncontrolled hypertension or significant cardiac disease
• Prefer non-controlled substances

Atomoxetine (Strattera)

Atomoxetine is the only FDA-approved non-stimulant for adult ADHD and should be the first-choice non-stimulant option, particularly when substance misuse risk exists or when 24-hour symptom coverage is needed. 1, 2, 6

Dosing:

• Start 40 mg orally once daily 1, 2
• Titrate every 7–14 days: 40 mg → 60 mg → 80 mg daily 1, 2
• Target dose: 60–100 mg/day 1, 2
• Maximum dose: lesser of 1.4 mg/kg/day or 100 mg/day 1, 2
• Can be given as single morning dose or split into morning and evening doses 1

Key characteristics:

• Effect size ≈0.7 (compared to stimulants ≈1.0) 1, 2
• Requires 6–12 weeks for full therapeutic effect (median 3.7 weeks) 1, 2
• Provides 24-hour symptom coverage 1, 2
• No abuse potential (uncontrolled substance) 1, 2
• FDA black-box warning for increased suicidal ideation in children and adolescents; monitor closely for suicidality, especially during first few months or at dose changes 1, 2, 6

Common adverse effects:

• Dry mouth (17–35% depending on CYP2D6 status) 6
• Decreased appetite (15–23%) 6
• Insomnia (11–19%) 6
• Nausea (6–13%) 6
• Constipation (7–11%) 6
• Erectile dysfunction (8–21% in males) 6
• Urinary hesitation (6%) 6
• Somnolence and fatigue (8–10%)—avoid in patients with prominent fatigue complaints 1, 6

Monitoring:

• Blood pressure and pulse at baseline and each visit 1, 2
• Suicidality screening at every visit 1, 2
• Height and weight 1, 2

Extended-Release Guanfacine (Intuniv)

Guanfacine is particularly useful when comorbid sleep disturbances, tics, anxiety, or oppositional symptoms are present, and it may actually lower blood pressure and heart rate—making it advantageous for patients with cardiovascular concerns. 1, 2, 4

Dosing:

• Start 1 mg once daily in the evening 1, 2
• Titrate by 1 mg weekly based on response and tolerability 1
• Target range: 0.05–0.12 mg/kg/day or 1–4 mg/day 1, 2
• Maximum dose: 7 mg/day 1
• Evening dosing preferred due to sedative effects 1, 2

Key characteristics:

• Effect size ≈0.7 1, 2
• Full effect observed within 2–4 weeks 1, 2
• FDA-approved as monotherapy or adjunctive therapy with stimulants 1, 2
• Decreases blood pressure and heart rate (opposite of stimulants) 4

Common adverse effects:

• Somnolence, sedation 2, 4
• Dry mouth 4
• Dizziness 4
• Bradycardia and hypotension 4

Critical safety warning:

• Never abruptly discontinue guanfacine—taper by 1 mg every 3–7 days to avoid rebound hypertension 1, 4

Extended-Release Clonidine (Kapvay)

Clonidine has similar properties to guanfacine (effect size ≈0.7,2–4 weeks to full effect, hypotensive effects) and is also FDA-approved as monotherapy or adjunctive therapy. 1, 2 Evening dosing is preferred due to sedation. 1 The same rebound hypertension risk applies—never discontinue abruptly. 4

Bupropion

Bupropion is explicitly positioned as a second-line agent for ADHD, to be considered only when two or more stimulants have failed or caused intolerable side effects, or when active substance abuse disorder is present. 1

Dosing:

• Start bupropion SR 100–150 mg daily or XL 150 mg daily 1
• Titrate to maintenance: SR 100–150 mg twice daily or XL 150–300 mg daily 1
• Maximum dose: 450 mg/day 1

Key characteristics:

• Effect size ≈0.7 (lower than stimulants) 1
• More rapid onset than atomoxetine but slower than stimulants 1
• May be useful when comorbid depression or smoking cessation is needed 1
• Not proven to effectively treat both ADHD and depression simultaneously—if both conditions persist, add an SSRI to the regimen 1

Common adverse effects:

• Headache, insomnia, anxiety 1
• Increased seizure risk at higher doses 1

Management of Comorbid Conditions

ADHD with Depression or Anxiety

Treat ADHD first with stimulants, even when depression or anxiety is present—depression and anxiety are not contraindications to stimulant therapy, and both conditions can be managed concurrently. 1, 2

Algorithm:

1. Initiate stimulant medication as first-line for ADHD 1, 2
2. Stimulants work within days, allowing rapid assessment of ADHD symptom response 1, 2
3. Treatment of ADHD alone may resolve comorbid depressive or anxiety symptoms in many cases by reducing functional impairment 1, 2
4. If ADHD symptoms improve but mood or anxiety symptoms persist after 6–8 weeks of optimized stimulant dosing, add an SSRI (fluoxetine or sertraline) to the stimulant regimen 1, 2
5. SSRIs and stimulants can be safely combined—there are no significant pharmacokinetic interactions 1, 2

Evidence supporting this approach:

• High-quality data from the MTA study show that stimulants do not exacerbate anxiety; response rates were actually higher in the anxious subgroup 1, 2
• No single antidepressant (including bupropion) is proven to effectively treat both ADHD and depression 1, 2

Exception: When the mood disorder is primary or accompanied by severe symptoms (psychosis, suicidality, marked neurovegetative signs), treat the mood disorder first before initiating ADHD medication. 1, 2

ADHD with Bipolar Disorder

For patients with confirmed bipolar disorder, mood stabilizers must be established and optimized before introducing stimulant medications to minimize the risk of manic episodes. 1, 2

Algorithm:

1. Achieve mood stabilization with mood stabilizers (e.g., divalproex, lithium) or atypical antipsychotics (e.g., aripiprazole) 1
2. Once mood is stable, initiate long-acting stimulant (methylphenidate or lisdexamfetamine) at low dose 1
3. Titrate slowly with close monitoring for emerging manic symptoms 1
4. If manic symptoms appear, stop stimulant immediately and refer for comprehensive psychiatric evaluation 1

Evidence: A randomized controlled trial showed that low-dose mixed amphetamine salts were safe and effective for comorbid ADHD only after mood symptoms were stabilized with divalproex. 1

ADHD with Substance Use Disorder

Exercise extreme caution when prescribing stimulants to patients with active or recent substance use disorder; consider long-acting formulations with lower abuse potential or non-stimulant alternatives as first-line. 1, 2

Preferred options:

• Atomoxetine (no abuse potential, uncontrolled substance) 1, 2
• Lisdexamfetamine (prodrug formulation reduces abuse potential) 1, 3
• Extended-release methylphenidate (Concerta) (OROS system resistant to tampering) 1, 2
• Extended-release guanfacine or clonidine (no abuse potential) 1, 2

If stimulants are used:

• Implement controlled substance agreements 5
• Use prescription drug monitoring programs 5
• Conduct urine drug screening at baseline and periodically 1, 2
• Schedule monthly follow-up visits 1
• Dispense smaller quantities (e.g., weekly or biweekly) 1

Psychosocial Interventions

Pharmacotherapy should always be combined with evidence-based psychosocial interventions to achieve optimal functional outcomes beyond core symptom reduction. 1, 2

Cognitive Behavioral Therapy (CBT) for ADHD:

• Most extensively studied and effective psychotherapy for adult ADHD 1, 2
• Focuses on time management, organization, planning, and adaptive behavioral skills 1, 2
• Increased effectiveness when combined with medication 1, 2

Mindfulness-Based Interventions (MBIs):

• Help most profoundly with inattention symptoms, emotion regulation, executive function, and quality of life 1, 2
• Recommended by Canadian ADHD Practice Guidelines and UK NICE guidelines 1

Psychoeducation:

• Essential component of comprehensive care 1, 2
• Educate patients and families about ADHD, treatment options, risks of untreated symptoms, proper medication storage, and disposal 3

Lifestyle Measures

• Regular sleep schedule to enhance medication effectiveness 1
• Stress management techniques 1
• Regular exercise (shows promise as adjunctive treatment) 1
• Dietary modifications (administer stimulants after meals to reduce appetite suppression) 1

Follow-Up Schedule

Titration phase (first 4–6 weeks):

• Weekly contact for symptom and side effect monitoring 1, 2
• Weekly ADHD rating scales (patient and informant) 1, 2
• Blood pressure and pulse at each dose adjustment 1, 2, 4

Maintenance phase:

• Monthly visits initially until symptom control stabilizes 1, 2
• Quarterly visits once stable 1, 2
• At each visit: blood pressure, pulse, weight, functional assessment across multiple settings 1, 2
• Annual comprehensive review of treatment efficacy and need for continued medication 2

Common Pitfalls to Avoid

• Do not assume the initial stimulant dose is adequate—70–80% of adults respond when properly titrated, and systematic titration to optimal effect is more important than strict mg/kg calculations 1, 2
• Do not switch stimulant classes after an inadequate trial—ensure the first agent has been titrated to maximum tolerated dose before labeling it as failed 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
• Do not prescribe immediate-release stimulants for "as-needed" use—ADHD requires consistent daily symptom control to prevent functional impairment across multiple settings 2
• Do not delay ADHD treatment because of comorbid mood symptoms—untreated ADHD worsens overall functional impairment and can exacerbate anxiety and depression 1, 2
• Do not assume a single antidepressant will effectively treat both ADHD and depression—no single antidepressant is proven for this dual purpose 1, 2
• Do not use MAO inhibitors concurrently with stimulants or bupropion—risk of hypertensive crisis 1, 2
• Do not abruptly discontinue guanfacine or clonidine—risk of rebound hypertension 1, 4