Can lamotrigine cause brain swelling?

October 10, 2025 •

3 min read

In 2010, the FDA issued a safety warning regarding lamotrigine (brand name Lamictal) after identifying 40 reported cases of aseptic meningitis between 1994 and 2009. This rare but serious side effect, characterized by inflammation of the protective membranes covering the brain and spinal cord, can in some instances lead to complications like brain swelling.

Quick Summary

Lamotrigine is linked to a very rare risk of aseptic meningitis, which is inflammation of the brain's protective membranes. Early recognition of symptoms, such as fever, headache, and neck stiffness, is crucial for timely medical intervention.

Key Points

Aseptic Meningitis is a Rare Risk: Lamotrigine can cause a very rare but serious side effect called aseptic meningitis, which is inflammation of the membranes covering the brain and spinal cord.
Potential for Brain Swelling: In extremely rare cases, the inflammation from aseptic meningitis can be severe enough to cause complications such as brain swelling.
Recognize Key Symptoms: Watch for warning signs like persistent headache, fever, stiff neck, nausea, vomiting, confusion, and sensitivity to light.
Act Quickly and Carefully: Seek immediate medical attention if symptoms occur. Do not stop lamotrigine abruptly without medical advice due to the risk of withdrawal seizures.
Recurrence Risk is Possible: Some patients who experienced aseptic meningitis had a more severe reaction when they were inadvertently re-exposed to lamotrigine.
HLH and DRESS are also Rare Risks: Other serious, rare immune system reactions like HLH and DRESS are also possible with lamotrigine use.
Follow Medical Guidance: Early recognition and proper medical management are key to a positive outcome if a severe adverse reaction occurs.

Understanding Lamotrigine's Link to Aseptic Meningitis

Aseptic meningitis is an inflammation of the protective membranes (meninges) covering the brain and spinal cord. Unlike infectious bacterial meningitis, aseptic meningitis is often caused by viruses, toxic agents, or certain medications, including lamotrigine. For individuals taking lamotrigine, this reaction is categorized as Drug-Induced Aseptic Meningitis (DIAM).

According to the FDA's 2010 safety communication, 40 cases of aseptic meningitis were reported in patients taking lamotrigine between 1994 and 2009, during which over 46 million prescriptions were dispensed. This highlights the extreme rarity of the condition. In most reported cases, symptoms resolved after the medication was discontinued. Significantly, 15 of these patients experienced a rapid recurrence of more severe symptoms when lamotrigine was reintroduced, pointing toward a hypersensitivity reaction.

The Mechanism of Hypersensitivity

The exact mechanism by which lamotrigine causes aseptic meningitis is not fully understood, but evidence suggests it's an immune-mediated hypersensitivity reaction. Upon initial exposure, the body may become sensitized to the drug. Subsequent re-exposure can trigger a more rapid and robust immune response, leading to inflammation. Some patients who developed this side effect also had underlying autoimmune conditions like systemic lupus erythematosus, suggesting potential increased susceptibility in those with compromised immune systems. During a reaction, analysis of cerebrospinal fluid (CSF) often shows an increase in white blood cells and protein, consistent with meningitis.

Symptoms of Lamotrigine-Induced Aseptic Meningitis

Recognizing the symptoms of drug-induced aseptic meningitis is critical for patient safety. Patients should contact their healthcare provider immediately if they experience any of the following while on lamotrigine:

Headache
Fever and chills
Stiff neck (nuchal rigidity)
Nausea and vomiting
Rash
Unusual sensitivity to light (photophobia)
Muscle pains (myalgias)
Drowsiness or confusion

In rare cases, severe inflammation from DIAM can lead to serious complications, including brain swelling. The symptoms often develop within days or weeks of starting the medication.

Other Serious Side Effects Associated with Lamotrigine

In addition to aseptic meningitis, lamotrigine is associated with other serious but rare side effects that require immediate medical attention. These include:

Serious skin reactions: This includes life-threatening conditions like Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). Symptoms include painful red or purple skin that peels and blisters, and painful sores on the mouth or eyes. The risk is higher in children, with higher starting doses, or when co-administered with valproate.
Hemophagocytic Lymphohistiocytosis (HLH): An excessively active immune system reaction that can cause severe inflammation throughout the body, potentially leading to organ damage and death. Signs include a persistent fever, rash, and swollen lymph nodes.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Another severe hypersensitivity reaction characterized by rash, fever, and multi-organ involvement (e.g., liver, kidneys, pancreas).
Overdose toxicity: An overdose can lead to severe central nervous system depression, ataxia (loss of coordination), seizures, and potentially fatal cardiac conduction delays.

How to Respond to a Suspected Adverse Reaction

If a patient suspects they are experiencing a serious side effect, including symptoms of aseptic meningitis, they must seek medical help immediately. However, it is crucial not to stop taking lamotrigine suddenly without medical supervision, as abrupt discontinuation can lead to severe withdrawal seizures. A doctor will evaluate the symptoms, perform diagnostic tests (such as a lumbar puncture for suspected meningitis), and decide whether to discontinue the medication and treat the reaction.

Comparison of Lamotrigine-Related Adverse Effects


Adverse Effect	Cause	Timeframe	Potential Consequences	Management
Aseptic Meningitis	Hypersensitivity reaction	1 to 42 days after starting	Brain swelling, hospitalization	Discontinue lamotrigine, supportive care
Serious Skin Rash (SJS/TEN)	Hypersensitivity reaction	2 to 8 weeks after starting	Permanent disability, death	Discontinue lamotrigine, emergency care
HLH / DRESS	Severe immune reaction	Weeks to months after starting	Multi-organ failure, death	Discontinue lamotrigine, intensive medical treatment
Overdose	Excessive dose	Hours after ingestion	Seizures, coma, cardiac arrest	Emergency medical care, supportive measures

Conclusion

While a direct causal link between lamotrigine and brain swelling is indirect and extremely rare, the medication can induce aseptic meningitis, which is an inflammation of the brain's protective membranes. Awareness of the symptoms—including headache, stiff neck, fever, and confusion—is the most crucial step for patient safety. Promptly contacting a healthcare provider and seeking immediate medical attention if these signs appear is essential, as is adhering to medical advice for discontinuation and management. Despite these risks, the overall benefit-risk profile of lamotrigine remains positive for most patients treating epilepsy or bipolar disorder. For additional safety information, consult the official FDA Drug Safety Communication regarding this risk.

Further Resources

FDA Drug Safety Communication: Aseptic meningitis associated with use of Lamictal (lamotrigine)

Frequently Asked Questions

Lamotrigine-induced aseptic meningitis is extremely rare. An FDA review from 1994 to 2009 identified only 40 cases among millions of prescriptions, indicating a very low incidence rate.

No. While both cause inflammation of the meninges, bacterial meningitis is an infection requiring immediate antibiotic treatment and is typically more severe. Aseptic meningitis is not caused by bacteria and is often associated with viruses, autoimmune diseases, or medication reactions like those from lamotrigine.

Common symptoms of lamotrigine-induced aseptic meningitis include a persistent headache, fever, stiff neck, nausea, vomiting, rash, and confusion.

The primary treatment is to stop taking lamotrigine under a doctor's supervision. In most cases, symptoms resolve after the medication is discontinued. Supportive care may also be administered to manage symptoms.

No, brain swelling (cerebral edema) is a potential, but rare, complication of severe aseptic meningitis. It is not an inevitable outcome for all cases of this drug-induced reaction.

You should never stop taking lamotrigine suddenly without consulting your healthcare provider. Abrupt discontinuation can trigger dangerous withdrawal seizures. If you have concerns or experience symptoms, speak to your doctor immediately.

Children and teenagers have a higher risk of developing the serious skin rashes associated with lamotrigine. While aseptic meningitis has been reported across various age groups, individuals with underlying autoimmune conditions may have an increased susceptibility to drug-induced hypersensitivity reactions.

Patients who develop aseptic meningitis should generally not be re-exposed to lamotrigine. Studies have shown that re-starting the medication can cause a rapid and more severe return of symptoms.