What are the steps to diagnose bupropion (Wellbutrin) toxicity?

Diagnosing Bupropion Toxicity

The diagnosis of bupropion toxicity requires identification of specific clinical manifestations including seizures, tachycardia, QRS prolongation, and neuropsychiatric symptoms, along with confirmation of elevated bupropion and metabolite levels when available.

Clinical Manifestations of Bupropion Toxicity

Neurological Symptoms

• Seizures - Most characteristic and concerning manifestation (0.8% in accidental extra doses, higher in intentional overdose) 1
• Status epilepticus - May occur in severe cases 2
• Clonic jerks and generalized seizures on EEG 2
• Agitation (8.2%) 1
• Tremor (7.1%) 1
• Hallucinations (0.4%) 1
• Dizziness (7.4%) 1
• Drowsiness (6.1%) 1

Cardiovascular Manifestations

• Tachycardia (5.5%) - Early sign that may resolve before other symptoms worsen 2, 1
• QRS prolongation - May develop hours after ingestion (up to 16 hours reported) 2
• Cardiogenic shock - Can develop late (32+ hours after ingestion) 2
• Cardiac arrest - Potential fatal complication 2

Gastrointestinal Symptoms

• Nausea and vomiting (6.7%) 1

Important Diagnostic Considerations

Timing of Symptom Development

• Extended-release formulations cause delayed and prolonged toxicity 3, 4
• QRS prolongation may develop up to 16 hours after ingestion 2
• Cardiac decompensation may occur 24-32+ hours after ingestion 2
• Resolution of tachycardia should NOT be interpreted as clinical improvement 2

Laboratory Testing

• Serum bupropion and hydroxybupropion levels (if available)
  • Toxic levels: bupropion >274 ng/ml, hydroxybupropion >4700 ng/ml 2
• Electrocardiogram - Monitor for QRS prolongation
• Electroencephalogram - If seizures are suspected
• Urine drug screen may show false-positive for amphetamines 5
• Consider confirmatory testing with gas chromatography/mass spectrometry 5

Risk Factors for Toxicity

• Co-ingestion with other medications (particularly olanzapine, MAOIs) 2
• Medications that lower seizure threshold 5
• Hepatic impairment (affects metabolism) 5
• Drug interactions with CYP2B6 inhibitors/inducers 5

Diagnostic Algorithm

1. Obtain detailed history:

   • Timing and amount of ingestion
   • Formulation (IR, SR, or XL) - XL has T(max) of ~5 hours vs ~1.5 for IR 4
   • Co-ingested substances
   • Pre-existing conditions

2. Physical examination focusing on:

   • Vital signs (tachycardia, hypertension)
   • Neurological status (seizures, agitation, tremor)
   • Cardiovascular assessment

3. Laboratory and diagnostic studies:

   • ECG (QRS interval measurement)
   • EEG if seizures are suspected
   • Bupropion and hydroxybupropion levels if available
   • Basic metabolic panel
   • Liver function tests

4. Monitoring:

   • Continuous cardiac monitoring for at least 24-36 hours
   • Serial ECGs to detect delayed QRS prolongation
   • Neurological checks

Pitfalls to Avoid

• Do not assume clinical improvement based on resolution of tachycardia - cardiac decompensation can occur hours to days after apparent improvement 2
• Do not rely on sodium bicarbonate to treat QRS prolongation in bupropion toxicity - evidence suggests it may be ineffective 2
• Do not discharge patients too early - extended-release formulations can cause delayed toxicity 3
• Do not mistake bupropion-induced seizures for brain death - full neurological recovery is possible even after severe presentations 2

Severity Assessment

• No effect: No symptoms (61.6% of accidental extra doses) 1
• Minor effect: Mild symptoms not requiring treatment (27.7%) 1
• Moderate effect: More pronounced symptoms requiring treatment (10.3%) 1
• Major effect: Life-threatening symptoms requiring intensive care (0.4%) 1

Remember that bupropion toxicity can be severe and potentially fatal, with seizures and cardiac complications being the most concerning manifestations. Extended-release formulations may cause delayed onset of symptoms and prolonged toxicity requiring extended monitoring.