Patient recently started on lacosamide for severe neuropathic pain now presents with nausea, headache, confusion, inability to ambulate and jaw pain—could lacosamide be responsible and how should it be managed?

Lacosamide Should Be Discontinued Immediately—It Is Likely Causing These Symptoms and Is Not Appropriate for Neuropathic Pain

Lacosamide is probably not effective for neuropathic pain and should be discontinued, with transition to pregabalin, gabapentin, or duloxetine as first-line alternatives. 1

Why Lacosamide Is the Culprit

The constellation of symptoms—nausea, headache, confusion, inability to ambulate (ataxia), and jaw pain—are classic adverse effects of lacosamide that occur in >10% of patients. 2

• Dizziness and ataxia are among the most common side effects, directly explaining the inability to ambulate 3, 2
• Nausea and headache are well-documented frequent adverse effects 3, 2
• Confusion represents CNS impairment, which lacosamide commonly causes 4
• Jaw pain (arthralgia) occurs in >10% of patients on lacosamide 2

The temporal relationship (recently started) strongly implicates lacosamide as the causative agent. 2

Why Lacosamide Should Not Have Been Prescribed

The American Academy of Neurology explicitly recommends that lacosamide should probably NOT be considered for treatment of painful diabetic neuropathy (Level B recommendation). 1

• Three Class III studies showed only minimal pain reduction (3-6% compared to placebo) with 400 mg/day 1
• Two studies showed NO significant difference versus placebo at 600 mg/day 1
• The evidence base concludes lacosamide is "possibly not effective" for neuropathic pain 1
• Even supportive guidelines note results are "equivocal" at best 1

Lacosamide is FDA-approved exclusively for focal-onset seizures, NOT for neuropathic pain. 3

Immediate Management Steps

1. Stop Lacosamide Immediately

• Do NOT taper if the patient has been on it for only a short time (days to few weeks), as withdrawal seizure risk is minimal in non-epileptic patients 3
• If used for >2-4 weeks, taper by 50 mg twice daily every 3-7 days to minimize any theoretical withdrawal effects 5
• The patient does not have epilepsy, so abrupt discontinuation carries minimal risk 3, 4

2. Provide Symptomatic Support

• Symptoms (nausea, dizziness, confusion, ataxia) should resolve within 2-5 days after discontinuation given lacosamide's elimination half-life 2
• Consider antiemetics for nausea if severe
• Ensure fall precautions until ataxia resolves

3. Obtain Baseline ECG Before Any Future Sodium Channel Blockers

• Lacosamide causes dose-related PR interval prolongation 3, 4
• While this patient is stopping lacosamide, document baseline cardiac conduction for future reference 5, 3

Appropriate Alternative Treatments for Neuropathic Pain

First-line agents with strong evidence:

Pregabalin (Level A Recommendation)

• Start 75 mg twice daily, titrate to 150-300 mg twice daily 1
• NNT of 4.04 for 600 mg/day and 5.99 for 300 mg/day 1
• Established as effective with Class I evidence 1
• Most common side effects: dizziness, somnolence, peripheral edema, weight gain 1

Gabapentin (Level B Recommendation)

• Start 300 mg daily, titrate to 900-3600 mg/day in divided doses 1
• Probably effective based on Class I evidence 1
• Better tolerated than lacosamide for neuropathic pain 1

Duloxetine (Level B Recommendation)

• Start 30 mg daily, increase to 60 mg daily after 1 week 1
• NNT of 4.9-5.2 for achieving ≥50% pain reduction 1
• Advantage: no weight gain, additional antidepressant effects 1
• Most common side effects: nausea (transient), somnolence, dizziness, constipation 1

Critical Pitfall to Avoid

Never use lacosamide for neuropathic pain when evidence-based alternatives exist. The American Academy of Neurology's Level B recommendation explicitly states it "should probably not be considered" for this indication. 1 Despite some open-label observational studies suggesting benefit 6, 7, these are contradicted by higher-quality placebo-controlled trials showing minimal to no effect. 1