In a patient with severe back, head, and jaw pain who has hyperprolactinemia while taking lacosamide, what is the most likely cause of the elevated prolactin and how should the neuropathic pain be managed?

Lacosamide Is Not the Cause of Hyperprolactinemia

Lacosamide is not a recognized cause of hyperprolactinemia, and the elevated prolactin in this patient requires systematic evaluation for other etiologies—most importantly medication review for dopamine antagonists, assessment for hypothyroidism, renal/hepatic disease, and consideration of a prolactinoma. 1, 2

Etiology of Hyperprolactinemia in This Patient

Medications Are the Most Common Reversible Cause

• Review all current medications immediately, focusing on dopamine antagonists (antipsychotics, antiemetics like metoclopramide or prochlorperazine), antidepressants (especially tricyclics), and antihypertensives, as these are among the most frequent causes of hyperprolactinemia. 1, 2, 3
• Lacosamide, an antiepileptic used for neuropathic pain, has no established association with hyperprolactinemia in the medical literature. 4
• Medication-induced hyperprolactinemia typically causes mild elevation (<100 ng/mL or <2,000 mU/L), though rare cases with dopamine antagonist combinations can produce higher levels. 1, 5

Exclude Secondary Medical Causes

• Measure TSH and free T4 to rule out primary hypothyroidism, which causes hyperprolactinemia in 43% of women and 40% of men with frank hypothyroidism through compensatory thyrotropin-releasing hormone hypersecretion. 1, 6
• Assess renal function (creatinine, eGFR), as chronic kidney disease causes hyperprolactinemia in 30–65% of adult patients due to increased prolactin secretion and reduced renal clearance. 1, 2
• Evaluate liver function if clinical suspicion exists, as severe hepatic disease is associated with hyperprolactinemia. 1

Consider Prolactinoma or Structural Lesions

• The degree of prolactin elevation guides imaging decisions: levels >4,000 mU/L (approximately >188 µg/L) strongly suggest a prolactinoma, while mild elevations may indicate stalk compression from non-functioning adenomas or other masses. 1, 6
• Order high-resolution pituitary MRI with and without contrast if prolactin remains elevated after excluding medications and secondary causes, or if the patient has visual symptoms, severe headaches, or prolactin >100 ng/mL. 6, 3, 7
• Request serial dilutions if MRI shows a large pituitary mass but prolactin seems paradoxically normal or only mildly elevated, as the "hook effect" occurs in approximately 5% of macroprolactinomas, producing falsely low measurements. 1, 6

Screen for Macroprolactinemia

• Test for macroprolactin when prolactin is mildly or incidentally elevated, as this benign condition (biologically inactive prolactin complexes) accounts for 10–40% of all hyperprolactinemia cases and requires no treatment. 1, 2

Management of Neuropathic Pain in This Context

Continue Lacosamide for Neuropathic Pain

• Lacosamide remains an appropriate and effective option for refractory neuropathic pain affecting the back, head, and jaw, with studies showing reduction in visual analogue scale scores from 7.7 to 4.8 after six months of treatment. 4
• The drug is well-tolerated with no serious side effects reported in observational trials, and only 10% of patients discontinued due to intolerance. 4
• Do not discontinue lacosamide based on the hyperprolactinemia, as there is no causal relationship. 4

Alternative Considerations Only If Lacosamide Fails

• If neuropathic pain is inadequately controlled or if lacosamide must be stopped for other reasons, consider standard neuropathic pain agents (gabapentinoids, tricyclic antidepressants, SNRIs), but be aware that tricyclic antidepressants can themselves cause hyperprolactinemia. 8

Diagnostic Algorithm

1. Immediately review all medications for dopamine antagonists, antidepressants, and antihypertensives. 1, 2, 3
2. Order TSH, free T4, creatinine, and eGFR to exclude hypothyroidism and renal disease. 1, 6
3. Measure macroprolactin if prolactin is mildly elevated (<100 ng/mL). 1, 2
4. If no medication or secondary cause is identified, or if prolactin is markedly elevated, proceed with pituitary MRI. 6, 3
5. If MRI shows a large mass with unexpectedly low prolactin, request serial dilutions to exclude the hook effect. 1, 6

Common Pitfalls to Avoid

• Do not assume lacosamide is causing the hyperprolactinemia—this drug has no established association with prolactin elevation. 4
• Do not overlook hypothyroidism, as it is a common and fully reversible cause that must be excluded in every case. 1, 6
• Do not miss occult dopamine antagonist use, including over-the-counter antiemetics (metoclopramide) or psychiatric medications the patient may not have disclosed. 1, 2, 3
• Do not forget to check for macroprolactinemia in mild cases, as treating biologically inactive prolactin is unnecessary and exposes patients to unneeded interventions. 1, 2