For a 55-year-old female with fatigue, motivational anhedonia, ADHD traits, and a history of stress as a primary caregiver, would bupropion or atomoxetine be the more appropriate medication to initiate?

Bupropion Over Atomoxetine for This Clinical Presentation

For this 55-year-old woman with fatigue, motivational anhedonia, ADHD traits, and caregiver stress, bupropion is the clear choice over atomoxetine. Atomoxetine's most common adverse effects are somnolence and fatigue, which would directly worsen her primary complaint of tiredness 1. Bupropion, in contrast, is inherently activating and works more rapidly than atomoxetine (which requires 6-12 weeks for full effect) 1, 2.

Critical Diagnostic Considerations Before Prescribing

This presentation suggests caregiver burnout and possible major depressive disorder rather than primary ADHD. The PHQ-9 score of 5 indicates minimal depression, but the 4-year history of primary caregiver stress with persistent fatigue and motivational anhedonia despite HRT strongly points to burnout as the primary driver 2. The GAD-7 of 2 rules out significant anxiety, which is important since bupropion can exacerbate anxiety 1, 2.

• ADHD traits without formal diagnosis do not warrant ADHD-specific pharmacotherapy according to current guidelines 2
• Full ADHD diagnosis requires symptoms causing impairment in at least two major settings with onset before age 12 per DSM-5 criteria 2
• If she has true ADHD, stimulants remain first-line with 70-80% response rates and the largest effect sizes from over 161 randomized controlled trials 1, 3

Why Bupropion is Superior in This Context

Bupropion addresses both the motivational/energy deficit and potential ADHD traits simultaneously. Low-quality evidence shows bupropion decreased ADHD symptom severity (standardized mean difference -0.50) and increased clinical improvement rates (RR 1.50) compared to placebo 4. More importantly for this patient, bupropion is the only antidepressant consistently shown to promote weight loss and has proven efficacy for both depression and ADHD 1.

• Start bupropion XL 150 mg daily, titrating to 300 mg daily after 1 week 2
• Bupropion works more rapidly than atomoxetine, allowing quicker assessment of response 1
• Tolerability is similar to placebo, with low-quality evidence showing no difference in withdrawal rates due to adverse effects (RR 1.20) 4

Why Atomoxetine is Inappropriate Here

Atomoxetine would be contraindicated given her chief complaint of fatigue. The medication's adverse effect profile directly opposes the treatment goal 1.

• Atomoxetine requires 6-12 weeks to achieve full therapeutic effect with median response time of 3.7 weeks 3
• Effect sizes are medium-range (approximately 0.7) compared to stimulants (1.0) 3
• Atomoxetine carries an FDA black box warning for suicidal ideation, requiring close monitoring 2
• Guidelines consistently position atomoxetine as second-line treatment when stimulants fail or are contraindicated 1

Monitoring and Safety Protocol

Screen for suicidality at baseline and throughout treatment, particularly given comorbid depressive symptoms and caregiver stress 2.

• Monitor for common side effects including headache, insomnia, and anxiety during the first 2-4 weeks 1, 2
• Close monitoring is essential in initial weeks as bupropion is inherently activating and can exacerbate anxiety or agitation 1, 2
• Maximum recommended dose is 450 mg per day 1
• The combination of bupropion with SSRIs has no significant drug-drug interactions if augmentation becomes necessary 1

Augmentation Strategy if Needed

If ADHD-related symptoms improve with bupropion but depressive symptoms persist after 4-6 weeks, add an SSRI to the regimen 2. SSRIs remain the treatment of choice for depression and are weight-neutral with long-term use 1.

• If bupropion provides inadequate ADHD symptom control after proper titration, consider adding a long-acting stimulant rather than switching to atomoxetine 1
• Stimulants can be safely combined with bupropion, though careful monitoring for side effects is necessary 1

Common Pitfalls to Avoid

Do not prescribe atomoxetine first-line when fatigue is a chief complaint, as this directly contradicts the medication's adverse effect profile 1. Do not assume bupropion alone will effectively treat both ADHD and depression in all patients—no single antidepressant is proven for this dual purpose, and bupropion is a second-line agent for ADHD treatment compared to stimulants 1.

• Do not underestimate the caregiver burden component, which may be contributing significantly to fatigue and should be addressed with psychosocial support alongside medication 1
• Avoid using MAO inhibitors concurrently with bupropion due to risk of hypertensive crisis 1
• Be especially cautious in patients with comorbid anxiety disorders, as bupropion's activating properties can worsen anxiety symptoms 1