What is the best course of action for a patient on 300mg Wellbutrin (bupropion) presenting with confusion, disorganized thought, possible hallucinations, and potential seizure activity after being treated for Attention Deficit Hyperactivity Disorder (ADHD)-like symptoms and low mood?

Immediate Discontinuation of Wellbutrin and Emergency Evaluation

Discontinue bupropion (Wellbutrin) 300mg immediately—this patient is presenting with classic neuropsychiatric toxicity including psychosis, confusion, and possible seizure activity, which are well-documented serious adverse effects of bupropion that require immediate drug cessation. 1

Immediate Actions

Stop Bupropion Now

• The FDA drug label explicitly states: "Discontinue bupropion hydrochloride extended-release tablets (XL) if these reactions occur" when patients develop delusions, hallucinations, psychosis, concentration disturbance, paranoia, and confusion. 1
• Bupropion carries specific warnings about psychosis and neuropsychiatric reactions, with symptoms including hallucinations (both auditory and visual), delusions, and confusion—all of which your patient is experiencing. 1
• The combination of confusion, disorganized thought, and possible seizure activity represents moderate-to-severe toxicity that mandates immediate cessation. 1

Emergency Department Evaluation Required

• This patient needs immediate emergency department evaluation despite leaving the college medical facility—she has potentially life-threatening complications. 1
• The unclear seizure history is particularly concerning as bupropion has a dose-dependent seizure risk (1/1000 at therapeutic doses), and seizures can be fatal or lead to status epilepticus. 2, 3
• Seizures from bupropion overdose can be recurrent and lead to hypoxia and death, requiring aggressive management. 3

Essential Laboratory and Diagnostic Workup

Immediate Labs to Order

• Comprehensive metabolic panel to assess electrolytes (particularly sodium, as hyponatremia can cause confusion and seizures), renal function, and hepatic function. 1
• Complete blood count to rule out infection as a contributor to altered mental status.
• Urine drug screen given her history of non-prescribed Adderall use—stimulant use combined with bupropion significantly increases seizure risk and can cause psychosis. 2, 1
• Serum bupropion level if available (though management is primarily supportive regardless of level). 4
• Blood glucose to rule out hypoglycemia as a cause of confusion.
• Thyroid function tests as thyroid disorders can present with psychiatric symptoms and confusion.

Additional Diagnostic Studies

• Head CT without contrast if seizure occurred or if there are focal neurological findings to rule out structural causes. 1
• EEG if seizure activity is suspected but unclear, as subclinical seizures can present with confusion and disorganized thought. 1
• ECG to assess for cardiac conduction abnormalities, as bupropion can cause tachycardia and dysrhythmias, though serious dysrhythmias are rare. 1, 4

Critical Risk Factors in This Case

Seizure Risk Amplification

• Your patient has multiple seizure risk factors: she was taking non-prescribed Adderall (stimulants lower seizure threshold), is on 300mg bupropion (maximum recommended dose), and may have underlying eating disorder behaviors (concentration issues and low mood in context of ADHD-like symptoms). 2, 1
• The FDA label specifically contraindicates bupropion in patients with conditions that predispose to seizures, including eating disorders (anorexia/bulimia), and warns about concomitant drugs that lower seizure threshold. 2, 1
• Doses above 450mg/day or single doses above 150mg significantly increase seizure risk, but even therapeutic doses carry risk. 2, 1

Psychosis and Hallucinations

• Bupropion-induced psychosis can occur at therapeutic doses and typically includes visual and auditory hallucinations, paranoia, and confusion—exactly what your patient is experiencing. 1
• These symptoms usually abate upon dose reduction or withdrawal, but the timeline varies. 1
• The fact that hallucinations were reported days ago suggests this is not an acute overdose but rather cumulative toxicity at the 300mg dose. 1

Management Algorithm

Phase 1: Immediate (Next 24 Hours)

1. Contact patient/family immediately to ensure bupropion is stopped and patient goes to ED for evaluation. 1
2. ED should provide supportive care: benzodiazepines for agitation/seizure prophylaxis, IV hydration, cardiac monitoring. 4, 3
3. Observation period of at least 24 hours given the extended-release formulation and potential for delayed seizures (seizures reported up to 21.5 hours post-ingestion in therapeutic errors). 4

Phase 2: Short-term (Days 2-7)

• Monitor for resolution of psychotic symptoms, which should improve within 3-5 days of discontinuation based on case reports. 5
• Do not restart bupropion—this patient has demonstrated serious neuropsychiatric toxicity. 1
• Assess for withdrawal symptoms from abrupt bupropion cessation, though these are typically mild (mood changes, irritability). 1

Phase 3: Ongoing Management

• Alternative treatment for depression/ADHD symptoms: Consider SSRIs for depression (avoid other agents that lower seizure threshold). 1
• For ADHD symptoms: If stimulants are needed, use with extreme caution given seizure history and only after complete resolution of acute symptoms. 6
• Screen for eating disorders given the contraindication with bupropion and the clinical presentation. 2, 1

Critical Pitfalls to Avoid

Do Not Restart Bupropion

• This patient has demonstrated serious adverse effects at 300mg—she is not a candidate for bupropion at any dose. 1
• Some patients may tolerate lower doses (150mg), but given the severity of her presentation (psychosis + possible seizure), rechallenge is contraindicated. 1

Do Not Assume This Will Resolve Without Intervention

• Bupropion-induced seizures can be fatal, and psychosis can persist or worsen without drug discontinuation. 3, 5
• The patient leaving the medical facility without evaluation significantly increases risk of adverse outcomes. 3

Do Not Overlook Polysubstance Use

• Her history of non-prescribed Adderall use is critical—stimulant use with bupropion dramatically increases seizure risk and can independently cause psychosis. 2, 1
• Urine drug screen is essential to guide management and assess ongoing stimulant use. 1

Documentation and Follow-up

• Document the adverse drug reaction and report to FDA MedWatch given the severity. 1
• Ensure patient understands bupropion is contraindicated for her going forward and document this in her chart with allergy/adverse reaction notation. 1
• Close psychiatric follow-up within 48-72 hours of ED discharge to reassess mental status and initiate alternative treatment. 1