What are the medication counselling points for dexamphetamine (dextroamphetamine) and atomoxetine in a 14-year-old patient with Attention Deficit Hyperactivity Disorder (ADHD) and a history of impulsive suicidal attempt?

Medication Counseling Points for Dexamphetamine and Atomoxetine in a 14-Year-Old with ADHD and History of Impulsive Suicidal Attempt

Critical Safety Warning: Atomoxetine and Suicidality

Atomoxetine carries an FDA black box warning for increased risk of suicidal ideation in children and adolescents, making it particularly concerning in this patient with a history of impulsive suicidal attempt. 1

• The FDA reports that atomoxetine increased suicidal ideation risk to 0.4% (5/1,357 patients) compared to 0% in placebo-treated patients in short-term trials 1
• Close monitoring for suicidality, clinical worsening, and unusual behavioral changes is mandatory, especially during the first few months of treatment or with dose changes 1, 2
• Families and caregivers must be advised of the need for close observation and immediate communication with the prescriber if any concerning symptoms emerge 1
• Co-morbidities occurring with ADHD may be associated with an increased risk of suicidal ideation and/or behavior 1

Treatment Algorithm Based on Risk Profile

Given this patient's history of impulsive suicidal attempt, dexamphetamine (a stimulant) should be the preferred first-line treatment over atomoxetine, with FDA-approved ADHD medications being strongly recommended for adolescents ages 12-18. 3

Rationale for Prioritizing Dexamphetamine:

• Stimulants have 70-80% response rates and work within days, allowing rapid assessment of efficacy 4
• The American Academy of Child and Adolescent Psychiatry recommends starting with stimulant medication for primary ADHD, as these are highly effective and may indirectly improve mood symptoms by reducing ADHD-related functional impairment 4
• Stimulants have the largest effect sizes (approximately 1.0) compared to atomoxetine (approximately 0.7) 4, 2
• Atomoxetine's black box warning for suicidal ideation makes it a higher-risk choice in this specific patient 1

When Atomoxetine Might Be Considered:

• If the patient has active substance abuse disorder or significant substance abuse risk 4
• If stimulants are contraindicated due to uncontrolled hypertension or symptomatic cardiovascular disease 4
• If the patient has comorbid tic disorders or Tourette's syndrome 2
• However, even in these scenarios, the suicidality risk must be carefully weighed against potential benefits 1

Dexamphetamine Counseling Points

Dosing and Administration:

• The American Academy of Child and Adolescent Psychiatry recommends starting at 5 mg in the morning, titrating upward by 5-10 mg weekly until symptoms are controlled 4
• Typical dosing ranges from 5 mg three times daily to 20 mg twice daily for adolescents 4
• Maximum daily doses generally reach 40 mg for amphetamine salts, though some patients may require up to 0.9 mg/kg or 65 mg total daily dose 4
• The medication works within days, allowing quick assessment of ADHD symptom response 4

Common Side Effects:

• Decreased appetite and weight loss (monitor height and weight at each visit) 4
• Insomnia (more common with stimulants than atomoxetine) 5, 6
• Headache 5
• Increased heart rate and blood pressure (monitor at baseline and each visit) 4
• Potential for afternoon/evening "rebound" symptoms as medication wears off 4

Critical Safety Monitoring:

• Monitor blood pressure and pulse at baseline and regularly during treatment 4
• Screen for suicidal ideation at each visit, given the patient's history 4
• Monitor sleep quality and appetite changes 4
• Assess for any worsening of mood symptoms or emergence of new psychiatric symptoms 4
• Never use with MAO inhibitors due to risk of severe hypertension and potential cerebrovascular accidents 4

Contraindications and Precautions:

• Avoid in patients with uncontrolled hypertension, symptomatic cardiovascular disease, or active psychosis/mania 4
• Exercise caution in patients with comorbid anxiety, though the MTA study showed stimulant response rates actually increased in subjects with comorbid anxiety disorder 4
• Be cautious about using stimulants in patients with substance abuse disorders (consider long-acting formulations with lower abuse potential) 4

Advantages:

• Rapid onset of action (works within days) 4
• Highest efficacy among ADHD medications 4
• Can be used to quickly assess ADHD symptom response 4
• May indirectly improve mood symptoms by reducing ADHD-related functional impairment 4

Atomoxetine Counseling Points (If Selected Despite Risks)

FDA Black Box Warning - Must Discuss:

Atomoxetine carries an FDA black box warning for increased risk of suicidal ideation in children and adolescents. 1

• Patients must be monitored closely for suicidality, clinical worsening, or unusual changes in behavior 1
• Families must understand the need for close observation and immediate communication with the prescriber 1
• This risk is particularly concerning given the patient's history of impulsive suicidal attempt 1

Dosing and Administration:

• Starting dose: 0.5 mg/kg/day for adolescents up to 70 kg or 40 mg/day for those over 70 kg 2
• Target dose: 1.2 mg/kg/day (maximum 1.4 mg/kg/day or 100 mg/day, whichever is lower) 2, 1
• Titration should occur every 7-14 days 2
• Can be administered as a single daily dose (morning or evening) or split into two evenly divided doses to reduce side effects 2, 7, 8
• Requires 6-12 weeks to achieve full therapeutic effect, significantly longer than stimulants which work within days 4, 2

Common Side Effects:

• Decreased appetite, nausea, vomiting, abdominal pain 2, 5, 9
• Somnolence and fatigue (more common with atomoxetine than stimulants) 5, 6
• Headache 2, 5
• Dizziness 8
• Dry mouth, constipation (in adults) 7, 8
• Initial weight loss, though this eventually returns to normal in the longer term 5

Critical Safety Monitoring:

• Monitor for suicidal ideation and clinical worsening, especially during the first few months or at dose changes 2, 1
• Monitor blood pressure and heart rate at baseline and regularly during treatment 4, 2
• Monitor height and weight, particularly in younger patients 4
• Assess for liver injury (rare but serious; three patients have had liver-related adverse events deemed probably related to atomoxetine) 5
• Screen for emergence of new psychiatric symptoms 4

Drug Interactions:

• CYP2D6 inhibitors (like paroxetine or fluoxetine) can increase atomoxetine levels, requiring dose adjustment 2, 5
• Approximately 7% of Caucasians and 2% of African Americans are poor CYP2D6 metabolizers, resulting in 10-fold higher drug exposure 2

Advantages:

• Non-controlled substance with negligible risk of abuse or diversion 7, 5, 8, 9, 6
• Provides "around-the-clock" symptom coverage without peaks and valleys 2
• Can be dosed once daily for convenience 2, 7, 8
• Particularly useful for patients with comorbid anxiety or tics 5, 6
• Does not typically exacerbate sleep problems (unlike stimulants) 5

Disadvantages:

• FDA black box warning for suicidal ideation in children and adolescents 1
• Delayed onset of action (6-12 weeks) compared to stimulants (days) 4, 2
• Smaller effect size (0.7) compared to stimulants (1.0) 4, 2
• Significantly less effective than extended-release methylphenidate and extended-release mixed amphetamine salts 5, 6
• Higher discontinuation rates due to adverse events compared to placebo 7, 8

Multimodal Treatment Approach

Pharmacological treatment must be combined with behavioral interventions and psychosocial supports, which are a necessary part of any treatment plan. 3

• Parent training in behavior management (PTBM) and/or behavioral classroom interventions should be implemented alongside medication 3
• Educational interventions and individualized instructional supports, including an Individualized Education Program (IEP) or 504 plan, are necessary 3
• Psychoeducation about ADHD and medication effects should be provided to the patient and family 2
• Given the history of suicidal attempt, concurrent mental health therapy is essential 4

Follow-Up and Monitoring Schedule

For Dexamphetamine:

• Weekly contact during initial titration phase 4
• Obtain weekly symptom ratings during dose adjustment 4
• Monitor blood pressure, pulse, weight, and height at each visit 4
• Screen for suicidal ideation at every visit given patient's history 4
• Once stabilized, monthly follow-up visits 4

For Atomoxetine (If Selected):

• Close monitoring for suicidality, especially during the first few months or with dose changes 1
• Monitor cardiovascular parameters at baseline and during dose adjustments 2
• Assess response after 6-12 weeks, as it has delayed onset of action 2
• Screen for suicidal ideation at every visit given both the medication's black box warning and patient's history 1
• Monitor for liver injury (check liver function tests if symptoms suggest hepatotoxicity) 5

Common Pitfalls to Avoid

• Do not select atomoxetine as first-line in this patient without carefully weighing the FDA black box warning for suicidal ideation against potential benefits 1
• Do not expect immediate results with atomoxetine—counsel families that 6-12 weeks are required for therapeutic effects 4, 2
• Do not assume a single medication will address both ADHD and any comorbid mood symptoms—if ADHD symptoms improve but mood symptoms persist, consider adding an SSRI 4
• Do not abruptly discontinue atomoxetine without tapering if liver injury or other serious adverse effects occur 2
• Do not overlook the need for multimodal treatment—medication alone is insufficient 3, 2
• Do not fail to obtain baseline cardiovascular parameters before starting either medication 4, 2