What are the recommended treatments for Attention Deficit Hyperactivity Disorder (ADHD) in adults?

Diagnosing and Treating ADHD in Adults

Diagnosis

Confirm ADHD diagnosis with documented symptom onset in childhood, as adult-onset ADHD is not recognized in DSM-IV criteria. 1

• Obtain collateral information from family members or close contacts, as adults with ADHD are unreliable reporters of their own behaviors 1
• Screen for psychiatric comorbidities including depression, anxiety, substance use disorders, and bipolar disorder before initiating treatment 1, 2
• Perform cardiovascular assessment including careful personal and family history of sudden death, arrhythmias, or cardiac disease, plus physical examination with baseline blood pressure and pulse 1, 3
• Assess family history and clinically evaluate for motor or verbal tics or Tourette's syndrome 3
• Screen for active substance abuse with urine drug screening if indicated 2

First-Line Pharmacological Treatment

Long-acting stimulant formulations (methylphenidate or amphetamines) are the gold standard first-line treatment, with 70-80% response rates and the strongest effect sizes for reducing core ADHD symptoms. 1

Stimulant Selection and Dosing

• Methylphenidate extended-release (e.g., Concerta): Start 18 mg once daily in the morning, titrate weekly based on response up to maximum 72 mg/day; provides 12-hour coverage with lower abuse potential due to tamper-resistant formulation 1, 3
• Methylphenidate immediate-release: 5-20 mg three times daily (preferably 30-45 minutes before meals), maximum 60 mg/day, average effective dose 20-30 mg/day; last dose before 6 PM to avoid insomnia 4, 3
• Amphetamine-based stimulants: Dexamphetamine 5 mg three times daily to 20 mg twice daily; preferred over methylphenidate based on comparative efficacy studies 1, 2
• Lisdexamfetamine (Vyvanse): Provides once-daily dosing with prodrug formulation that reduces abuse potential 5

Why Long-Acting Formulations Are Preferred

• Better medication adherence due to once-daily dosing 1
• Lower risk of rebound effects and more consistent symptom control throughout the day 1
• Reduced diversion potential and abuse risk, critical for patients with executive dysfunction 1
• Around-the-clock coverage extending beyond work hours, addressing functional impairment in multiple settings 1

Stimulant Optimization Strategy

• Individual response to methylphenidate versus amphetamine is idiosyncratic: approximately 40% respond to both, 40% respond to only one 1
• If inadequate response to one stimulant class after 6 weeks at adequate dose, switch to the other class before considering non-stimulants 1, 6
• Methylphenidate shows 78% improvement versus 4% placebo response when dosed at approximately 1 mg/kg total daily dose 1, 4

Second-Line Non-Stimulant Options

Atomoxetine is the only FDA-approved non-stimulant for adult ADHD and serves as the primary second-line option when stimulants are contraindicated, not tolerated, or ineffective. 1, 7

Atomoxetine Dosing and Monitoring

• Target dose: 60-100 mg daily for adults, maximum 1.4 mg/kg/day or 100 mg/day (whichever is lower) 1, 8
• Start 40 mg daily, increase after minimum 3 days to target dose 8
• Requires 2-4 weeks to achieve full therapeutic effect, with median time to response of 3.7 weeks; probability of improvement may continue increasing up to 52 weeks 1, 8
• Effect size approximately 0.7 compared to stimulants' effect size of 1.0 1
• FDA black box warning: Monitor closely for suicidal ideation, clinical worsening, and unusual behavioral changes, especially during first few months or at dose changes 1

Other Non-Stimulant Alternatives

• Extended-release guanfacine: 1-4 mg daily, effect size around 0.7; particularly useful if sleep disturbances or tics present; administer in evening due to somnolence 1
• Extended-release clonidine: Similar efficacy to guanfacine; can be used as monotherapy or adjunctive therapy with stimulants 1
• Bupropion: 100-150 mg twice daily (SR) or 150-300 mg daily (XL), maximum 450 mg/day; particularly useful when depression is comorbid, though it is a second-line agent for ADHD compared to stimulants 1, 4
• Viloxazine: Emerging option with favorable efficacy and tolerability in clinical trials, though limited long-term data 1, 7

Treatment Algorithm for Specific Clinical Scenarios

ADHD with Comorbid Depression

• If depression is mild or secondary to ADHD: Start with stimulant trial, as improving ADHD symptoms may indirectly improve mood by reducing functional impairment 1, 2
• If ADHD symptoms improve but depression persists: Add SSRI to stimulant regimen; no significant drug-drug interactions between stimulants and SSRIs 1
• If depression is severe or primary: Treat depression first with SSRI, then address ADHD symptoms 1, 2
• SSRIs remain the treatment of choice for depression, are weight-neutral with long-term use, and can be safely combined with stimulants 1

ADHD with Comorbid Anxiety

• Anxiety does not contraindicate stimulant use; stimulants can indirectly reduce anxiety related to functional impairment by improving executive function 1
• Monitor anxiety symptoms regularly to ensure they are not worsening 1
• If anxiety persists after ADHD treatment, consider adding SSRI or psychosocial interventions 2
• Avoid benzodiazepines, as they may reduce self-control and have disinhibiting effects 1

ADHD with Substance Use Disorder History

• Exercise extreme caution when prescribing stimulants; consider long-acting formulations with lower abuse potential (e.g., Concerta, lisdexamfetamine) or atomoxetine as first-line 1, 2, 3
• Implement urine drug screening to ensure compliance and detect any return to substance use 1
• Schedule monthly follow-up visits to assess response and monitor for substance use relapse 1
• Atomoxetine is an uncontrolled substance and may be preferred in this population 1

Monitoring Parameters

• Cardiovascular: Blood pressure and pulse at baseline and regularly during treatment 1, 3
• Growth parameters: Height and weight, particularly in younger patients 1
• Psychiatric: Suicidality (especially with atomoxetine), anxiety symptoms, mood changes 1
• Functional outcomes: Reduction in core ADHD symptoms and improvement in functional domains (work, relationships, daily activities) 1
• Adverse effects: Sleep disturbances, appetite changes, headache, insomnia, anxiety 1, 3

Common Adverse Effects

• Stimulants: Loss of appetite, insomnia, anxiety, increased blood pressure and heart rate 1, 3
• Atomoxetine: Nausea, decreased appetite, dizziness, somnolence, sexual dysfunction 8
• Bupropion: Headache, insomnia, anxiety, seizure risk at higher doses 1
• Alpha-2 agonists: Somnolence, fatigue, hypotension, bradycardia 1

Critical Contraindications and Warnings

• Absolute contraindications for stimulants: Known hypersensitivity, concurrent MAOI use or within 14 days of MAOI discontinuation (risk of hypertensive crisis) 3
• Relative contraindications: Uncontrolled hypertension, symptomatic cardiovascular disease, active psychosis or mania, active substance abuse 1
• High abuse potential: Methylphenidate and amphetamines are Schedule II controlled substances; assess each patient's risk for abuse, misuse, and addiction before prescribing 3
• Never use MAOIs concurrently with stimulants or bupropion due to risk of severe hypertension and potential cerebrovascular accidents 1

Treatment Duration and Reassessment

• Evaluate periodically the need to continue treatment, including possible intervals without medication 2
• Long-term studies show that stimulant therapy has sustained beneficial effects and is well tolerated, with favorable effects maintained during follow-up periods up to 4 years 9
• Reassess each patient's risk of abuse, misuse, and addiction throughout treatment and frequently monitor for signs and symptoms 3

Non-Pharmacological Interventions

• Cognitive Behavioral Therapy (CBT): Most extensively studied psychotherapy for adult ADHD, focusing on time management, organization, planning, and adaptive behavioral skills; more effective when combined with medication 1
• Mindfulness-Based Interventions: Show evidence for managing inattention symptoms, emotion regulation, executive function, and quality of life 1
• Evidence for non-pharmacological treatments as monotherapy remains preliminary; combination with medication is recommended 10