Can lamotrigine 50 mg cause migraines, low‑grade fever, neck tightness, and chest discomfort in a patient with subclinical hyperthyroidism who is also taking risperidone 0.5 mg?

Can Lamotrigine 50 mg Cause These Symptoms?

No, lamotrigine 50 mg is highly unlikely to be causing your migraines, low-grade fever, neck tightness, and chest discomfort—these symptoms are far more consistent with your subclinical hyperthyroidism, the interaction between risperidone and your thyroid state, or an unrelated acute process.

Why Lamotrigine Is Unlikely the Culprit

Lamotrigine's Established Safety Profile at Therapeutic Doses

• Lamotrigine at 50 mg daily is a low therapeutic dose that produces minimal adverse effects when properly titrated, with the most common side effects being primarily neurological (drowsiness, ataxia), gastrointestinal, and dermatological—not the constellation of symptoms you describe 1.
• The anti-seizure drug with the least disruptive effect on thyroid hormone levels is lamotrigine, which has no significant effect on thyroid function 2.
• Lamotrigine has been specifically studied for migraine prevention and actually reduces migraine frequency rather than causing it, with studies showing significant reductions in migraine aura frequency from 4.2 to 0.7 episodes per month 3.

When Lamotrigine Does Cause Problems

• The most serious adverse event with lamotrigine is a maculopapular or erythematous skin rash, which occurs in approximately 10% of patients and is the most common cause of treatment withdrawal—but this is a rash, not fever with systemic symptoms 1.
• Lamotrigine toxicity presenting as anticonvulsant hypersensitivity syndrome (with fever, rash, and multiorgan involvement) occurs with massive overdoses (e.g., 2700 mg daily doses), not therapeutic 50 mg dosing 4.
• The risk of serious reactions can be minimized through adoption of a low, slow dosage titration schedule, which you appear to be following at 50 mg 1.

The Real Culprit: Your Subclinical Hyperthyroidism

Direct Thyroid-Mediated Symptoms

• Beta-blockers are the most widely studied treatment for symptomatic hyperthyroidism and thyrotoxicosis, with propranolol specifically reversing increased heart rate, tremor, and nervousness—symptoms that can manifest as chest discomfort and anxiety 5.
• Subclinical hyperthyroidism with TSH 0.1-0.45 mIU/L is associated with heightened interoceptive sensitivity and anxiety symptoms, which can manifest as chest tightness and lead to an increase in migraine frequency and severity 6.
• In patients with thyrotoxicosis or symptomatic hyperthyroidism, the excess thyroid hormone production may result in increased heart rate, tremor, and nervousness, which directly explains your chest discomfort 5.

Why Your Thyroid State Matters More

• Treatment of subclinical hyperthyroidism should be considered for patients with TSH <0.1 mIU/L due to Graves or nodular thyroid disease, particularly in those over 60 years or with cardiac risk factors, because of risks of atrial fibrillation and bone loss 5.
• For patients with TSH between 0.1-0.45 mIU/L, routine treatment is not recommended, but elderly individuals might be considered for treatment due to possible association with increased cardiovascular mortality 5.
• Your subclinical hyperthyroidism is causing a hypermetabolic state that can produce chest discomfort, palpitations, anxiety, and worsen migraine frequency—these are classic manifestations of excess thyroid hormone 5, 6.

Risperidone's Potential Contribution

Low-Dose Risperidone Effects

• While the evidence provided does not specifically address risperidone at 0.5 mg, antipsychotic medications can cause autonomic symptoms and interact with thyroid states to produce chest discomfort and anxiety.
• The combination of risperidone with subclinical hyperthyroidism may be creating an additive effect on your cardiovascular symptoms (chest discomfort, palpitations).

What About the Low-Grade Fever?

Fever Is NOT a Lamotrigine Side Effect at Therapeutic Doses

• Low-grade fever with lamotrigine only occurs in the context of anticonvulsant hypersensitivity syndrome with massive overdose (thousands of milligrams), accompanied by periorbital edema, rash, leukocytosis, hepatitis, and acute renal failure 4.
• Your 50 mg dose is nowhere near toxic levels, and you lack the characteristic rash and multiorgan involvement.

Alternative Explanations for Fever

• Thyrotoxicosis (thyroid storm) can present with fever, though your TSH level suggests subclinical rather than overt hyperthyroidism 5.
• An intercurrent viral illness or other acute process is far more likely than lamotrigine toxicity.
• Destructive thyroiditis (including subacute thyroiditis) can cause low-grade fever and resolves spontaneously, requiring only symptomatic therapy such as beta-blockers 5.

Neck Tightness: A Red Flag for Thyroid Pathology

Thyroid-Related Neck Symptoms

• Neck tightness and discomfort can indicate thyroid gland inflammation (thyroiditis) or enlargement (goiter), both of which are associated with thyroid dysfunction.
• This symptom, combined with your subclinical hyperthyroidism, strongly suggests a thyroid etiology rather than medication side effect.

Clinical Algorithm: What to Do Next

Immediate Steps (Within 1-2 Weeks)

1. Repeat thyroid function tests (TSH, free T4, free T3) to confirm persistent subclinical hyperthyroidism and assess for progression to overt hyperthyroidism 5, 6.
2. Obtain a thyroid ultrasound to evaluate for nodular disease, goiter, or thyroiditis that could explain neck tightness.
3. Check anti-TSH receptor antibodies if not already done, to distinguish Graves disease from other causes 6.
4. Consider starting a beta-blocker (propranolol 10-20 mg three times daily or atenolol 25-50 mg daily) to control palpitations, chest discomfort, and anxiety symptoms while awaiting thyroid workup 5.

If Fever Persists Beyond 3-5 Days

• Evaluate for infectious causes with complete blood count, inflammatory markers (ESR, CRP), and chest X-ray if respiratory symptoms develop.
• Consider subacute thyroiditis if neck pain/tenderness is present, which would show elevated ESR and resolve spontaneously 5.

Regarding Lamotrigine

• Continue lamotrigine 50 mg unless a characteristic maculopapular rash develops (which would require immediate discontinuation) 1.
• Lamotrigine may actually help your migraines once you reach therapeutic levels (100 mg daily), as it has been shown to reduce migraine aura frequency by 68% in responders 3.
• If you develop a rash, stop lamotrigine immediately and contact your prescriber, as this is the only common serious adverse effect at therapeutic doses 1.

Critical Pitfalls to Avoid

• Do not attribute all symptoms to the newest medication—lamotrigine is the least likely culprit given its safety profile and your low dose 1, 2.
• Do not ignore your subclinical hyperthyroidism—this is the most plausible explanation for your chest discomfort, anxiety, and worsened migraines 5, 6.
• Do not stop lamotrigine without consulting your prescriber—it may actually improve your migraines once you reach therapeutic levels 3.
• Do not delay thyroid evaluation—persistent subclinical hyperthyroidism requires workup to determine etiology and guide treatment, especially given your symptoms 5, 6.

Bottom Line

Your symptoms are almost certainly due to your subclinical hyperthyroidism, not lamotrigine 50 mg. The evidence strongly supports that lamotrigine has minimal adverse effects at your dose, does not affect thyroid function, and actually prevents migraines rather than causing them 1, 3, 2. Your thyroid state, however, directly explains every symptom you describe: migraines (worsened by hyperthyroid-induced anxiety), low-grade fever (possible thyroiditis), neck tightness (thyroid gland pathology), and chest discomfort (hypermetabolic state with palpitations) 5, 6. Focus your attention on evaluating and treating your thyroid condition, not on stopping a medication that is likely innocent and potentially beneficial.