What is the recommended treatment for Attention Deficit Hyperactivity Disorder (ADHD) with medications?

ADHD Medication Treatment

First-Line Pharmacotherapy

Stimulant medications—specifically methylphenidate or amphetamine formulations—are the recommended first-line treatment for ADHD due to their superior efficacy and rapid onset of action. 1

Stimulant Selection and Initiation

• Methylphenidate is the most commonly used stimulant for ADHD treatment and should be initiated at 5-10 mg in the morning after breakfast for adults, with gradual titration by 5-10 mg increments weekly based on response and tolerability 1, 2
• For children and adolescents up to 70 kg, start at approximately 0.5 mg/kg/day and increase after a minimum of 3 days to a target dose of approximately 1.2 mg/kg/day, with a maximum of 1.4 mg/kg or 100 mg daily, whichever is less 3
• Amphetamine-based medications are an appropriate alternative first-line option, initiated at 10 mg once daily in the morning with 5 mg weekly increments as needed, up to a maximum of 50 mg daily for adults 1
• The maximum dose of methylphenidate typically ranges from 60-72 mg/day depending on formulation 4, 1

Long-Acting Formulations Preferred

• Long-acting formulations of methylphenidate (such as OROS methylphenidate) provide 8-12 hours of symptom control and are superior for maintaining adherence compared to immediate-release formulations 1, 5
• Extended-release preparations eliminate the need for multiple daily doses during school or work hours, significantly improving compliance rates which can otherwise range from 20-65% noncompliance with immediate-release formulations 6
• The behavioral effects of methylphenidate occur when plasma concentrations are increasing, with maximum effects at 1-3 hours for immediate-release formulations 5

Second-Line Non-Stimulant Options

Atomoxetine

• Atomoxetine is the primary non-stimulant alternative when stimulants are contraindicated, not tolerated, or ineffective 1
• Initiate at 40 mg/day (or 0.5 mg/kg/day in children up to 70 kg) and titrate after a minimum of 3 days to a target dose of 80 mg/day (or 1.2 mg/kg/day), with a maximum of 100 mg/day 3
• Atomoxetine has a slower onset of action compared to stimulants but offers the advantage of no abuse potential 1
• For patients taking strong CYP2D6 inhibitors (paroxetine, fluoxetine, quinidine) or known CYP2D6 poor metabolizers, maintain the initial dose of 0.5 mg/kg/day for 4 weeks before increasing to 1.2 mg/kg/day if symptoms fail to improve 3

Alpha-2 Adrenergic Agonists

• Extended-release guanfacine or extended-release clonidine can be used as adjunctive therapy with stimulants or as monotherapy, with effect sizes around 0.7 7
• When combining clonidine with stimulants, start with 0.05 mg at bedtime and increase slowly, never exceeding 0.3 mg/day 1
• A full medical history of the patient and first-degree family members should be obtained before starting clonidine, as a history of sudden death, repeated fainting, or arrhythmias may rule out its use 1

Bupropion

• Bupropion is a second-line, non-stimulant alternative, initiated at 150 mg once daily in the morning and titrated to 150-300 mg daily based on response, with a maximum of 450 mg per day 1
• Screen for seizure risk factors, eating disorders, seizure history, or abrupt alcohol/benzodiazepine withdrawal, as bupropion lowers seizure threshold and is contraindicated in these situations 1
• Avoid combining bupropion with stimulants until further safety data are available 1

Critical Pre-Treatment Assessment

Cardiovascular Screening

• Before initiating stimulant therapy, evaluate cardiovascular status including baseline blood pressure, pulse, and assessment for symptomatic cardiovascular disease 1, 2
• Stimulants are contraindicated in patients with symptomatic heart disease, as sudden death has occurred in people with heart defects or serious heart disease 2
• Regular vital sign monitoring (blood pressure, pulse) is necessary throughout treatment with stimulants 7

Psychiatric Screening

• Screen for a personal or family history of bipolar disorder, mania, or hypomania prior to initiating atomoxetine or stimulant treatment 3
• Assess for current or past substance abuse, as this represents a relative contraindication requiring close supervision, and consider non-stimulant alternatives in patients with active substance use disorders 1
• Evaluate for psychosis, mania, bipolar illness, depression, or family history of suicide, as new or worsening psychiatric symptoms can occur with stimulant treatment 2

Monitoring During Treatment

• Schedule monthly visits until symptoms stabilize, assessing both therapeutic response and adverse effects at each dose adjustment using standardized rating scales 1
• Common adverse effects requiring monitoring include decreased appetite, gastrointestinal symptoms, sleep disturbances, and cardiovascular effects such as increased blood pressure and heart rate 1, 8
• Allow adequate time between dose adjustments (minimum one week) to properly evaluate response before escalating 1
• If the first stimulant trial fails, switch to an alternative stimulant formulation (e.g., methylphenidate to amphetamine or vice versa) before moving to non-stimulants 1

Regional Guideline Variations

• Western guidelines (NICE, AAP) recommend stimulants as first-line treatment, while the 2022 Japanese guidelines recommend school environment management and psychosocial treatment as first-line, with pharmacological treatment as second-line 4
• Malaysian, Singaporean, and Indian guidelines recommend methylphenidate as first-line medication when pharmacotherapy is indicated, with atomoxetine as an alternative 4
• In Malaysia and Singapore, only methylphenidate (immediate-release, extended-release, and long-acting formulations) and atomoxetine are approved for ADHD treatment in children over 6 years 4

Critical Pitfalls to Avoid

• Do not start at excessively high doses, as this increases adverse effects and reduces adherence; begin conservatively, especially in older patients who may have increased sensitivity 1
• Do not discontinue stimulants abruptly for "drug holidays" during important events, as symptoms return rapidly upon discontinuation 1
• Do not use methylphenidate with monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping an MAOI 2
• Afternoon doses of methylphenidate may need to be higher than morning doses to prevent symptom attenuation later in the day 1
• Atomoxetine capsules should not be opened; they must be taken whole 3