Does an elevated prolactin level help diagnose seizures in a patient with moderate to severe anemia taking bupropion (bupropion hydrochloride)?

Elevated Prolactin for Seizure Diagnosis

Elevated prolactin levels can help differentiate true epileptic seizures from psychogenic seizures, but this test has significant limitations and should not be relied upon as the sole diagnostic criterion. 1

Diagnostic Utility of Postictal Prolactin

Prolactin rises in approximately 60% of complex partial seizures due to propagation of epileptic activity from the temporal lobe to the hypothalamic-pituitary axis. 1 This means that:

• A negative prolactin test does NOT rule out a seizure - 40% of true epileptic seizures will not show prolactin elevation 1
• Prolactin typically fails to rise after psychogenic seizures, making it most useful for distinguishing epileptic from non-epileptic events 1
• Prolactin cannot subclassify seizure types - it cannot tell you what kind of epileptic seizure occurred 1

Critical Timing Considerations

The timing of prolactin measurement is crucial but not well-standardized. Prolactin levels must be drawn in the postictal period to be interpretable, as baseline prolactin can be elevated for numerous non-seizure reasons. 1

Important Confounders in This Clinical Context

Bupropion and Seizure Risk

Bupropion significantly lowers the seizure threshold and is a well-established cause of drug-induced seizures. 2, 3 Key facts:

• Bupropion accounts for 1.4% of all new-onset seizures presenting to emergency departments and represents the third leading cause of drug-related seizures after cocaine and benzodiazepine withdrawal 3
• Seizures occur even at therapeutic doses (≤450 mg/day) - all four bupropion-related seizures in one study occurred at recommended dosing 3
• The seizure risk is dose-dependent, with rates of approximately 0.1% at doses up to 300 mg/day 4, 5
• Delayed seizures can occur up to 24 hours after bupropion XL ingestion, and 32% of initial seizures occur more than 8 hours post-ingestion 6

Anemia and Prolactin

Moderate to severe anemia does not typically cause hyperprolactinemia. However, you must consider other causes of elevated baseline prolactin that could confound interpretation: 7

• Medications are among the most common causes of hyperprolactinemia through dopamine antagonism 7
• Hypothyroidism causes hyperprolactinemia in 40% of men and 36% of women with frank primary hypothyroidism 7
• Chronic kidney disease causes hyperprolactinemia in 30-65% of patients due to increased secretion and reduced renal clearance 7

Clinical Algorithm for This Patient

If this patient had a witnessed seizure while on bupropion:

1. Discontinue bupropion immediately and permanently - it is absolutely contraindicated after a seizure has occurred 4, 5
2. Prolactin measurement may support the diagnosis if drawn within the appropriate postictal window, but a negative result does not exclude seizure 1
3. The clinical history and witnessed event are more reliable than prolactin for diagnosis in this context 1
4. Switch to an alternative antidepressant without seizure risk (SSRI, mirtazapine, or vortioxetine) 5

Common Pitfalls to Avoid

• Do not rely on prolactin alone - sensitivity is only 60% for epileptic seizures 1
• Do not restart bupropion after any seizure - this is an absolute contraindication regardless of prolactin results 4, 5
• Do not assume a normal prolactin rules out seizure - 40% of true seizures will have normal postictal prolactin 1
• Do not forget that repetitive seizures or status epilepticus may show DECREASED prolactin release due to diminished propagation of ictal activity 1

In summary: Prolactin can provide supportive evidence but has insufficient sensitivity to rule out seizures. In a patient on bupropion with a clinical seizure, the medication is the likely culprit regardless of prolactin levels, and must be discontinued permanently. 5, 1, 3