How should I manage a 21‑year‑old woman with anorexia nervosa, major depressive disorder, and ADHD who is on sertraline 50 mg daily and atomoxetine 40 mg daily and now presents with nausea and vomiting likely due to atomoxetine?

Management of Atomoxetine-Induced Nausea and Vomiting

Administer atomoxetine with food and consider dose reduction to 25-40 mg daily, as nausea and vomiting are among the most common adverse effects of atomoxetine and typically improve with these simple interventions. 1, 2

Immediate Management Strategy

First-Line Interventions

• Take atomoxetine with food or shortly after meals, as this significantly reduces gastrointestinal adverse effects without compromising efficacy 1, 2
• Temporarily reduce the dose to 25 mg daily and re-titrate more slowly over 2-3 weeks, as the current 40 mg dose may be too aggressive for this patient's tolerance 1, 3
• Ensure adequate hydration and small frequent meals to minimize nausea severity 2

Pharmacologic Antiemetic Support

• Consider short-term metoclopramide 10 mg three times daily if nausea persists despite dose adjustment, as dopamine antagonists are effective for medication-induced nausea 1
• Ondansetron 4-8 mg as needed can be added for breakthrough nausea without significant drug interactions 1

Critical Considerations in This Patient Population

Anorexia Nervosa Context

• Monitor weight closely, as atomoxetine commonly causes decreased appetite and weight loss (reported in clinical trials), which is particularly concerning in a patient with anorexia nervosa 1, 2, 3
• The combination of atomoxetine-induced appetite suppression and pre-existing anorexia nervosa creates significant risk for further weight loss and metabolic complications 4, 5
• Consider whether ADHD treatment is essential at this time, as stabilizing nutritional status may need to take priority over ADHD symptom management 4

Drug Interaction Alert

• Sertraline is a moderate CYP2D6 inhibitor that can elevate atomoxetine levels by 2-4 fold, potentially explaining the severe nausea in this patient 1, 3
• Approximately 7% of patients are poor CYP2D6 metabolizers with significantly higher plasma levels and increased adverse effects; this patient may functionally be a poor metabolizer due to the sertraline interaction 1, 3
• If nausea persists despite dose reduction, the atomoxetine-sertraline combination may be pharmacologically incompatible for this patient 1

Alternative ADHD Management Options

If Nausea Persists Despite Interventions

• Switch to methylphenidate extended-release, which has comparable efficacy to atomoxetine but a different adverse effect profile with lower rates of nausea 3, 4
• Consider alpha-2 agonists (guanfacine or clonidine) as non-stimulant alternatives, though these have less robust efficacy data in adults 1
• Temporarily discontinue ADHD medication and focus on behavioral interventions until eating disorder symptoms stabilize 4

Sertraline Considerations

• Switching from sertraline to escitalopram may reduce both SSRI-related nausea and the CYP2D6 interaction, as escitalopram has minimal effects on CYP450 enzymes and lower gastrointestinal side effect rates 6, 7
• If switching antidepressants, taper sertraline over 10-14 days to minimize discontinuation syndrome while initiating escitalopram 6, 8

Monitoring Parameters

Essential Follow-Up

• Reassess nausea severity within 3-5 days of dose reduction or medication adjustment 2, 3
• Weekly weight checks are mandatory given the dual risk of atomoxetine-induced appetite suppression and underlying anorexia nervosa 4, 5
• Monitor for suicidal ideation closely, as atomoxetine carries a black-box warning for increased suicidal thoughts in young adults, and this patient has comorbid depression 1, 3
• Check blood pressure and heart rate at each visit, as atomoxetine causes modest increases that may be poorly tolerated in malnourished patients 1, 2

Common Pitfalls to Avoid

• Do not continue atomoxetine at the current dose hoping tolerance will develop—nausea and vomiting are the most common reasons for treatment discontinuation and rarely improve without intervention 2, 3
• Do not add a proton pump inhibitor, as atomoxetine-induced nausea is centrally mediated rather than due to gastric acid 1
• Do not overlook the sertraline-atomoxetine interaction, which may be the primary driver of intolerable side effects in this case 1, 3
• Do not prioritize ADHD treatment over eating disorder stabilization—inadequately treated anorexia nervosa has higher morbidity and mortality than untreated ADHD 4, 5