First-Line Medications for ADHD
Stimulant medications—specifically methylphenidate or amphetamines in long-acting formulations—are the first-line pharmacological treatment for ADHD, with demonstrated efficacy in 70-80% of patients and superior effect sizes compared to all other options. 1, 2
Stimulant Selection and Formulation
Primary Recommendations
Long-acting stimulant formulations are strongly preferred over immediate-release preparations due to better medication adherence, lower risk of rebound effects, more consistent symptom control throughout the day, and reduced diversion potential 2
Methylphenidate options include:
Amphetamine options demonstrate superior efficacy in adults with larger effect sizes (SMD -0.79 vs -0.49 for methylphenidate) and are preferred based on comparative efficacy studies 2
Choosing Between Stimulant Classes
- Response to methylphenidate versus amphetamine is idiosyncratic: approximately 40% respond to both, 40% respond to only one class 2
- If inadequate response to one stimulant class, trial the other class before considering non-stimulants 2
- Both classes have effect sizes of approximately 1.0, significantly superior to non-stimulants (effect size ~0.7) 2
Dosing and Titration Strategy
Methylphenidate Dosing
- Start low and titrate weekly based on response to achieve maximum benefit with tolerable side effects 2
- Target dose: approximately 1 mg/kg total daily dose, with maximum 60 mg daily in adults 2
- Response rates reach 78% versus 4% placebo when properly dosed 2
- For Concerta specifically: 18 mg is equivalent to methylphenidate 5 mg three times daily 2
Amphetamine Dosing
- Pediatric patients 6+ years: Start 5 mg once or twice daily, increase by 5 mg weekly until optimal response, rarely exceeding 40 mg total daily 3
- Adults: Start 10 mg daily, increase by 5-10 mg weekly, with maximum 40-50 mg daily depending on formulation 2, 3
- Titrate upward by 5-10 mg weekly until symptoms resolve, as 70-80% respond when properly titrated 2
Non-Stimulant Second-Line Options
When to Consider Non-Stimulants
Non-stimulants should be considered when: 2
- Active substance abuse disorder present
- Inadequate response or intolerable side effects to both stimulant classes
- Comorbid tics or severe anxiety
- Patient or family preference against stimulants
- Uncontrolled hypertension or symptomatic cardiovascular disease
Atomoxetine (FDA-Approved Non-Stimulant)
- Only FDA-approved non-stimulant for ADHD in both pediatric and adult patients 4
- Target dose: 60-100 mg daily in adults; 0.5-1.2 mg/kg/day in children 2
- Median time to response: 3.7 weeks, with full therapeutic effect requiring 6-12 weeks 2
- Effect size: approximately 0.7 (medium-range compared to stimulants at 1.0) 2
- Advantages: 24-hour coverage, non-controlled substance, addresses comorbid anxiety 2
- Critical warning: Increased risk of suicidal ideation in children/adolescents requires close monitoring 4
Alpha-2 Adrenergic Agonists
- Extended-release guanfacine or clonidine: Effect sizes around 0.7, useful as monotherapy or adjunctive therapy with stimulants 2
- Guanfacine dosing: Start 1 mg nightly, titrate by 1 mg weekly to target 0.05-0.12 mg/kg/day 2
- Particular utility: Comorbid sleep disorders, oppositional symptoms, or as adjunctive for residual ADHD symptoms 2
- Adverse effects: Relatively frequent somnolence/fatigue, administer in evening 2
Other Non-Stimulant Options
- Bupropion: Anecdotal benefits, particularly useful when depression is comorbid 2
- Viloxazine: Newer serotonin-norepinephrine modulating agent with demonstrated efficacy, though limited adult data 2
Monitoring Requirements
Essential Parameters
- Cardiovascular monitoring: Blood pressure and pulse at baseline, at each medication adjustment, and periodically during stable treatment 2
- Growth parameters: Height and weight monitoring in children 2
- Functional assessment: Evaluate improvement across multiple settings (school/work, home, social environments) 2
- Side effect monitoring: Appetite suppression, sleep disturbances, anxiety symptoms 2
Contraindications
Absolute contraindications for stimulants include: 2
- Active stimulant abuse (though daily treatment can reduce relapse risk in stable substance dependence) 2
- Symptomatic cardiovascular disease
- Uncontrolled hypertension
- Tachyarrhythmias
Critical Clinical Pitfalls
Do not use immediate-release stimulants "as needed": ADHD requires consistent daily symptom control; sporadic dosing fundamentally misunderstands ADHD pathophysiology and leaves patients vulnerable to repeated functional failures 2
Do not abandon stimulants prematurely: Optimize dose and trial both stimulant classes before declaring treatment failure; 70-80% respond when properly titrated 2
Do not prescribe stimulants to adults with comorbid active substance abuse without careful consideration, though stable patients in treatment may benefit 2
Obtain collateral information: Adults with ADHD are unreliable reporters of their own behaviors; gather information from family members or close contacts 2
Screen for cardiovascular risk: Establish baseline cardiovascular status before initiating stimulants, particularly in adults 2
Comprehensive Treatment Approach
Medication should be combined with behavioral interventions: Parent training in behavior management and behavioral classroom interventions enhance outcomes, particularly in children 2, 4
Treatment is typically long-term: ADHD frequently persists into adulthood with negative impacts across life domains if untreated; periodic reassessment determines whether continued treatment remains necessary 2
Do not discontinue effective 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