What is the step‑by‑step algorithm for initiating stimulant therapy in an adult (≥18 years) with attention‑deficit/hyperactivity disorder, including diagnostic confirmation, cardiac and psychiatric contraindication screening, baseline electrocardiogram, titration of immediate‑release methylphenidate, monitoring parameters, and subsequent options if the stimulant is ineffective or not tolerated?

Algorithm for Initiating Stimulant Therapy in Adult ADHD

Step 1: Diagnostic Confirmation

Before prescribing any stimulant, confirm the ADHD diagnosis using DSM-5 criteria with documentation of symptoms causing impairment in at least two major settings (work, home, social). 1 Obtain collateral information from family members or significant others whenever possible to verify childhood onset and current symptom patterns. 1

Use a validated self-report screening tool such as the Adult ADHD Self-Report Scale (ASRS) Part A to systematically assess current symptoms before initiating medication. 1 The diagnosis requires evidence of childhood-onset symptoms (before age 12), though retrospective assessment can be challenging in adults. 1

Step 2: Pre-Treatment Screening and Baseline Assessment

Cardiac Contraindication Screening

Obtain a detailed cardiovascular history including any history of syncope, chest pain, palpitations, exercise intolerance, or family history of premature cardiovascular death, arrhythmias, or structural heart disease. 1 Measure baseline blood pressure and pulse in both seated and standing positions. 1, 2

Absolute contraindications to stimulant therapy include: 1, 3

• Known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, or coronary artery disease
• Symptomatic cardiovascular disease or uncontrolled hypertension
• Concurrent MAOI use or use within the preceding 14 days
• Active psychosis or mania
• Known hypersensitivity to methylphenidate or amphetamines
• Glaucoma, hyperthyroidism

Routine baseline ECG is NOT recommended for low-risk adults without cardiac symptoms or risk factors. 2 Reserve ECG for patients with concerning cardiac history, abnormal physical examination findings, or significant cardiovascular risk factors. 2

Psychiatric Contraindication Screening

Screen for active substance use disorders, particularly current stimulant abuse or uncontrolled substance use. 1, 2 A history of substance use disorder is a relative contraindication requiring caution and consideration of long-acting formulations with lower abuse potential, but is not an absolute contraindication. 1

Prior to initiating stimulants, screen for risk factors for developing a manic episode, including personal or family history of bipolar disorder. 1, 3 If bipolar disorder is confirmed, mood stabilizers must be established and optimized before starting any stimulant medication. 1

Assess for comorbid depression and anxiety, which are common but not contraindications to stimulant therapy—both conditions can be managed concurrently with ADHD. 1

Additional Baseline Measures

Document baseline height and weight (particularly relevant for younger adults). 1, 2 Record all prior ADHD treatments including previous medications, dosages, duration, response, side effects, and adherence patterns. 1, 2

Step 3: Medication Selection and Initial Dosing

First-Line Stimulant Choice

Amphetamine-based stimulants (mixed amphetamine salts or lisdexamfetamine) are preferred as first-line therapy for adults, achieving 70-80% response rates with the largest effect sizes. 1 Methylphenidate is an equally effective alternative with comparable efficacy. 1

Strongly prefer long-acting formulations over immediate-release for adults due to better adherence, lower rebound effects, more consistent symptom control, and reduced diversion potential. 1, 2

Starting Doses

For immediate-release methylphenidate: Start at 5 mg twice daily (before breakfast and lunch). 1, 2, 3

For extended-release methylphenidate (Concerta/OROS): Start at 18 mg once daily in the morning. 1

For mixed amphetamine salts immediate-release: Start at 2.5 mg once or twice daily. 1, 2

For Adderall XR: Start at 10 mg once daily in the morning. 1

For lisdexamfetamine (Vyvanse): Start at 20-30 mg once daily in the morning. 1

Administer stimulants 30-45 minutes before meals when using immediate-release formulations. 3 Long-acting formulations should be taken in the morning to minimize insomnia risk. 1

Step 4: Systematic Titration Protocol

Weekly Titration Schedule

Increase the dose weekly based on symptom response and tolerability until optimal ADHD symptom control is achieved or dose-limiting adverse effects appear. 1, 2 Stimulant effects manifest within days, allowing rapid assessment of efficacy. 1

Titration increments: 1, 2

• Methylphenidate immediate-release: increase by 5-10 mg weekly
• Methylphenidate extended-release (OROS): increase by 18 mg weekly
• Amphetamine salts: increase by 5-10 mg weekly
• Lisdexamfetamine: increase by 10-20 mg weekly

Do NOT base dosing on mg/kg body weight calculations—systematic titration to the lowest effective dose that yields clinical benefit is the preferred approach. 1 Approximately 70% of patients achieve optimal response when proper titration protocols are followed. 1

Maximum Therapeutic Doses

Methylphenidate: Maximum 60 mg daily for adults. 1, 3 Typical therapeutic range is 20-30 mg daily for immediate-release (divided 2-3 times daily) or 30-37.5 mg daily for extended-release. 1

Mixed amphetamine salts: Maximum 50 mg daily, though doses up to 60-65 mg may be employed when lower doses are ineffective and no dose-limiting side effects occur. 1 Typical therapeutic range is 10-50 mg daily. 1

Lisdexamfetamine: Maximum 70 mg daily. 1

Step 5: Monitoring During Titration (Weeks 1-4)

Weekly Contact Schedule

Conduct weekly contact (phone or in-person) during the first 2-4 weeks of dose adjustments to evaluate symptom response and side effects. 1 At each weekly contact, obtain ADHD rating scales to track inattention, hyperactivity, impulsivity, and functional impairment across work, home, and social settings. 1

Vital Sign Monitoring

Measure blood pressure and pulse at every dose adjustment visit. 1, 2 If blood pressure rises above 130/80 mmHg, dose reduction or addition of antihypertensive therapy is required. 2

Side Effect Assessment

Systematically inquire about common stimulant side effects at each visit: 1, 3

• Insomnia and sleep quality
• Appetite suppression and weight changes
• Headache
• Mood changes, irritability, or anxiety
• Cardiovascular symptoms (palpitations, chest pain)
• Tics or abnormal movements
• Rare but serious: psychotic symptoms, priapism

Weigh the patient at each visit to detect appetite suppression effects. 1, 2

Step 6: Maintenance Phase Monitoring

Follow-Up Schedule After Dose Stabilization

Schedule monthly appointments until symptoms are fully stabilized on a consistent dose. 1 Once response is robust and adherence is good, transition to quarterly visits (every 3 months). 1, 2

Increase visit frequency when: 1

• Significant side effects arise
• Comorbid disorders cause substantial impairment
• Medication adherence is problematic
• Therapeutic response remains suboptimal

Ongoing Monitoring Parameters (Every Maintenance Visit)

At each maintenance visit, assess: 1, 2

• Blood pressure and pulse (quarterly in stable adults)
• Weight and appetite
• ADHD symptom ratings using standardized scales
• Functional outcomes across work, home, and social domains
• Side effect profile (sleep, appetite, mood, cardiovascular symptoms)
• Screen for medication misuse, diversion, or substance use disorders
• Monitor for tolerance development (rare)

Step 7: Managing Inadequate Response

If Response is Suboptimal After Adequate Titration

If inadequate response occurs after reaching therapeutic doses of one stimulant class, switch to the other stimulant class (methylphenidate ↔ amphetamine) before considering non-stimulants. 1 Approximately 40% of patients respond to both classes, while another 40% respond preferentially to only one class. 1

Apply the same systematic titration approach when switching between stimulant classes. 1

Addressing Comorbid Conditions

If ADHD symptoms improve but residual mood or anxiety symptoms persist after 6-8 weeks of optimized stimulant dosing, add an SSRI (fluoxetine or sertraline) to the stimulant regimen. 1 This combination is well-established, safe, and lacks significant pharmacokinetic interactions. 1

Untreated anxiety or depressive disorders can masquerade as apparent ADHD treatment failure—assess and treat these comorbidities before deeming the stimulant ineffective. 1

Step 8: Second-Line Options if Stimulants Fail or Are Not Tolerated

When to Consider Non-Stimulants

Reserve non-stimulant agents for patients who have failed or could not tolerate two or more stimulant trials, or who have an active substance use disorder. 1

Non-Stimulant Options

Atomoxetine: Target dose 60-100 mg daily (maximum 1.4 mg/kg/day or 100 mg/day, whichever is lower). 1 Start at 40 mg daily and titrate every 7-14 days. 1 Requires 6-12 weeks to achieve full therapeutic effect (much slower than stimulants). 1 Effect size approximately 0.7 compared to 1.0 for stimulants. 1

Extended-release guanfacine: 1-4 mg daily, particularly useful when sleep disturbances, tics, or disruptive behaviors are present. 1 Requires 2-4 weeks for full effect. 1

Extended-release clonidine: Similar indications to guanfacine. 1

Bupropion: Consider only when two or more stimulants have failed or when active substance abuse disorder is present. 1 Positioned as a second-line agent with smaller effect sizes than stimulants. 1

Common Pitfalls to Avoid

Do not under-dose stimulants. Community treatment programs using lower doses and less frequent monitoring produce inferior outcomes compared with optimal, closely monitored medication management. 1

Do not stop titration prematurely. Systematic titration protocols enable approximately 70% of patients to reach optimal outcomes. 1

Do not assume a single antidepressant will effectively treat both ADHD and depression. No single antidepressant is proven for this dual purpose—treat ADHD with stimulants first, then add an SSRI if mood symptoms persist. 1

Do not prescribe benzodiazepines for anxiety in ADHD patients. They may reduce self-control and have disinhibiting effects. 1

Do not combine stimulants with MAOIs or start within 14 days of MAOI discontinuation due to risk of hypertensive crisis. 1, 3