A patient on Strattera (atomoxetine) for one week, previously tolerated, now presents with euphoria, vomiting, and mydriasis—what emergency management is recommended?

Emergency Management of Suspected Atomoxetine Toxicity

This patient requires immediate discontinuation of Strattera and emergency department evaluation for possible atomoxetine toxicity, drug interaction, or serotonin syndrome, as the constellation of euphoria, vomiting, and mydriasis is not consistent with typical atomoxetine adverse effects and suggests a potentially serious reaction. 1

Immediate Actions Required

Discontinue Medication and Seek Emergency Care

• Stop atomoxetine immediately and transport the patient to the emergency department for evaluation, as these symptoms (feeling "high," vomiting, dilated pupils) are atypical for atomoxetine and may indicate toxicity or a serious drug interaction 1
• The typical adverse effects of atomoxetine include nausea, vomiting, fatigue, decreased appetite, abdominal pain, and somnolence—but euphoria and mydriasis are not characteristic features 1

Emergency Department Evaluation

• Obtain vital signs with particular attention to heart rate and blood pressure, as atomoxetine can cause tachycardia and hypertension, which may be exaggerated in toxicity 1
• Perform an ECG to assess for QRS widening, as atomoxetine overdose has been associated with mild cardiac toxicity and QRS prolongation 2
• Check serum atomoxetine levels if available, though management should not be delayed awaiting results 2
• Obtain a comprehensive drug screen and medication history to identify potential drug interactions, particularly with CYP2D6 inhibitors (such as SSRIs like paroxetine or fluoxetine) that can dramatically increase atomoxetine levels 1, 3

Differential Diagnosis Considerations

Atomoxetine Toxicity

• Atomoxetine overdose can cause seizures and mild cardiac toxicity with QRS widening, though euphoria is not a typical feature 2
• Approximately 7% of the population are poor CYP2D6 metabolizers with significantly higher plasma levels and longer half-lives, which may lead to increased adverse effects even at therapeutic doses 1, 3
• If the patient is a poor metabolizer or taking CYP2D6 inhibitors, atomoxetine concentrations can be 10-fold higher than in extensive metabolizers 3

Serotonin Syndrome

• Consider serotonin syndrome if the patient is taking any concomitant serotonergic medications (SSRIs, SNRIs, tramadol, trazodone, dextromethorphan, St. John's Wort), as atomoxetine increases norepinephrine and dopamine in the prefrontal cortex 1, 4
• Classic triad includes mental status changes (euphoria could represent altered mental status), neuromuscular hyperactivity (mydriasis is consistent with autonomic instability), and autonomic instability 4
• Look specifically for clonus (especially inducible ankle clonus), hyperreflexia, and myoclonus, which occur in 57% of cases and are highly diagnostic 4

Drug Interaction or Co-ingestion

• Question the patient about all medications, supplements, and over-the-counter drugs, particularly CYP2D6 inhibitors that can elevate atomoxetine levels 1, 3
• Consider co-ingestion of stimulants or other substances that could explain euphoria and mydriasis 4

Supportive Management

Symptomatic Treatment

• Administer benzodiazepines (lorazepam 2-4 mg) for agitation if present, as benzodiazepines are effective for acute agitation and have a favorable safety profile 1
• Provide antiemetics for persistent vomiting 1
• Monitor for seizures, as atomoxetine overdose has been reported to cause tonic-clonic seizures 2

Cardiovascular Monitoring

• Continuous cardiac monitoring is warranted given the potential for tachycardia, hypertension, and QRS prolongation 1, 2
• Serial ECGs should be obtained, with particular attention to QRS interval (widening >100 ms suggests significant toxicity) 2

Observation Period

• Observe for at least 24 hours, as atomoxetine has a half-life of 5.2 hours in extensive metabolizers but 21.6 hours in poor metabolizers 3
• Monitor for progression of symptoms, particularly development of fever, severe muscle rigidity, confusion, or seizures that would indicate worsening toxicity or serotonin syndrome 4

Critical Pitfalls to Avoid

• Do not assume this is a typical adverse effect simply because the patient tolerated atomoxetine previously—new drug interactions, changes in metabolism, or inadvertent overdose must be considered 1, 3
• Do not overlook over-the-counter medications and supplements as potential contributors to drug interactions, particularly those containing dextromethorphan or St. John's Wort 4
• Do not delay emergency evaluation while attempting to determine the exact cause—the combination of altered mental status, vomiting, and mydriasis requires urgent assessment 4, 2
• Do not restart atomoxetine until the cause of this reaction is fully investigated and alternative explanations are ruled out 1