What is the best non-stimulant medication to start a 33-year-old female with Attention Deficit Disorder (ADD) on, who is experiencing side effects from Adderall (amphetamine and dextroamphetamine)?

Best Non-Stimulant Medication for Adult Female with ADD and Adderall Side Effects

Atomoxetine (Strattera) is the recommended first-line non-stimulant medication for this 33-year-old female, starting at 40 mg daily and titrating to 80-100 mg daily over 2-4 weeks. 1, 2

Dosing Algorithm for Atomoxetine

• Initial dose: Start at 40 mg once daily in the morning 1, 2
• Titration schedule: After a minimum of 3 days, increase to 80 mg daily (can be given as single morning dose or split into morning and late afternoon/evening doses) 2
• Target dose: 80-100 mg daily, with maximum dose of 100 mg daily 1, 2
• Timeline for response: Full therapeutic effects require 6-12 weeks, so patience is essential 1

Why Atomoxetine is the Best Choice

Atomoxetine is the only FDA-approved non-stimulant specifically studied and approved for adult ADHD, with demonstrated 28-30% reduction in ADHD symptom scores versus 18-20% with placebo in controlled adult trials 1, 3. This represents an effect size of approximately 0.7, which while slightly weaker than stimulants (effect size ~1.0), is clinically meaningful 4.

Key advantages for this patient include:

• Non-controlled substance status eliminates abuse potential and allows easier prescription refills 1, 3
• Continuous 24-hour symptom coverage without the peaks and valleys seen with stimulants 1
• Lower risk of exacerbating anxiety compared to stimulants, important if anxiety contributed to Adderall side effects 1
• No cardiovascular stimulation like that seen with amphetamines 5

Critical Safety Monitoring Requirements

FDA Black Box Warning: Monitor closely for suicidal ideation, especially during the first few weeks of treatment 1, 2. This is based on pooled analyses showing 0.4% risk of suicidal ideation in atomoxetine-treated patients versus 0% in placebo 2.

Additional monitoring parameters:

• Baseline assessment: Blood pressure, heart rate, weight, and suicidality screening 1
• 2-4 week follow-up: Vital signs, side effects, and early response 1
• 6-12 week assessment: ADHD symptom scales and functional impairment to determine therapeutic response 1
• Ongoing monitoring: Quarterly vital signs and continuous suicidality monitoring 1

Common Side Effects to Anticipate

The most common adverse events in adults are 2, 3:

• Dry mouth, nausea, and decreased appetite (gastrointestinal effects are transient if dose is increased slowly) 4, 5
• Insomnia (despite being a non-stimulant) 3
• Constipation and urinary retention 3
• Sexual dysfunction (approximately 2% of patients) 5
• Modest increases in heart rate and blood pressure (generally well tolerated) 3

Critical pitfall: Increasing the dose too rapidly causes increased gastrointestinal symptoms and somnolence 4. Always wait at least 3 days between dose increases 2.

Alternative Non-Stimulant Options if Atomoxetine Fails

Second-Line: Extended-Release Guanfacine

Switch to guanfacine extended-release if atomoxetine is ineffective after 12 weeks at therapeutic dose or causes intolerable side effects 1. Guanfacine has an effect size of approximately 0.7, similar to atomoxetine 4.

• Dosing: Start at approximately 0.1 mg/kg once daily (1-4 mg tablets available) 1
• Timing: Administer in the evening due to sedation risk 1
• Specific advantages: Particularly useful if the patient has comorbid anxiety or sleep disturbances that may have contributed to Adderall intolerance 1
• Common side effects: Somnolence and dry mouth 4

Third-Line: Bupropion

Consider bupropion if both atomoxetine and guanfacine have failed, or if comorbid depression is present 1. Bupropion is a norepinephrine and dopamine reuptake inhibitor shown to be more effective than placebo in adults with ADHD 4.

• Dosing for SR formulation: Start 100-150 mg daily, titrate to 100-150 mg twice daily 4
• Dosing for XL formulation: Start 150 mg daily, titrate to 150-300 mg daily (maximum 450 mg daily) 4
• Important caveat: Bupropion is NOT FDA-approved for ADHD, so this is off-label use 1

Fourth-Line: Viloxazine (Qelbree)

Viloxazine is a newer FDA-approved non-stimulant option for adults with ADHD 1. It has been shown to be significantly more efficacious than placebo 4.

• Dosing: Start at 200 mg once daily, maximum dose 600 mg once daily 1
• Evidence base: Newer medication with less long-term data compared to atomoxetine 1

Why NOT to Use Stimulants as Alternatives

Since this patient is already experiencing side effects from Adderall (an amphetamine), switching to another stimulant like methylphenidate would carry similar risks 4. The guideline recommendation is clear: use stimulants as first-line therapy and non-stimulants as second-line therapy 4. This patient has already failed first-line therapy due to side effects, making non-stimulants the appropriate next step.

Contraindications to Atomoxetine

Do not use atomoxetine if the patient has 1:

• Severe cardiovascular disease
• Narrow-angle glaucoma
• Current or recent (within 2 weeks) use of monoamine oxidase inhibitors