Lamotrigine Side Effects: What to Expect and When to Call Your Doctor

Lamotrigine (Lamictal) is generally well-tolerated by most patients, but it carries some important safety warnings that every patient starting the medication should understand. Most side effects are mild and improve as your body adjusts. A few, however, require immediate medical attention. This guide walks through all of them so you know what to watch for.

The Boxed Warning: Serious Skin Rash

The FDA requires lamotrigine's package insert to carry a "boxed warning" — the most serious type of drug safety warning. The warning is specifically about life-threatening skin rashes, including:

Stevens-Johnson Syndrome (SJS): A severe disorder causing painful blistering of the skin, mucous membranes (mouth, eyes, genitals), and internal organs. Can be fatal if not treated immediately.

Toxic Epidermal Necrolysis (TEN): An even more severe form of SJS, with widespread skin loss affecting over 30% of body surface area. Life-threatening and requires ICU-level burn care.

Risk factors for serious rash include: starting at too high a dose, increasing the dose too rapidly, taking lamotrigine with valproate (which doubles lamotrigine blood levels), and being a pediatric patient (children have higher serious rash rates than adults). Almost all serious rashes appear within the first 2-8 weeks of starting therapy, though they can occur later.

What to do: If you develop any rash — even a mild one — contact your prescriber immediately. Do not wait to see if it goes away on its own. If you develop blistering skin, mouth sores, eye redness or pain, or skin peeling, call 911 or go to the emergency room immediately.

Common Side Effects (Usually Mild and Temporary)

These side effects are reported most often and typically improve within the first few weeks as your body adjusts to the medication:

Dizziness: Most common during initiation and dose increases. Take lamotrigine with food if dizziness is bothersome. Avoid driving until you know how the medication affects you.

Headache: Common in the first weeks. Usually resolves without dose adjustment.

Nausea: Usually mild; often resolved by taking the medication with food.

Drowsiness / sleepiness: Some patients feel sedated, especially at higher doses. Taking the dose at bedtime may help.

Ataxia (unsteady gait / coordination problems): Usually dose-related and improves with dose reduction if needed.

Diplopia (double vision) or blurred vision: Reported more commonly when lamotrigine is combined with carbamazepine. Often dose-related.

Tremor or shakiness: Mild tremor may occur, particularly at higher doses.

Serious Side Effects That Require Prompt Medical Attention

Beyond the boxed rash warning, the following serious side effects require you to contact your doctor right away:

DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms): A severe multiorgan allergic reaction affecting the liver, kidneys, heart, and lungs. Symptoms include fever, swollen lymph nodes, widespread skin rash, and organ dysfunction. Can occur weeks after starting the medication.

Aseptic meningitis: Rare but documented. Symptoms include severe headache, neck stiffness, fever, sensitivity to light, nausea, and confusion. Higher risk in patients with connective tissue disorders like lupus.

Blood disorders: Lamotrigine can rarely cause neutropenia, anemia, thrombocytopenia, or aplastic anemia. Symptoms include unusual bruising, bleeding, persistent fatigue, or frequent infections.

Suicidal thoughts or behavior: The FDA requires all antiepileptic drugs to carry a warning about increased risk of suicidal ideation and behavior. This is a class effect — if you experience new or worsening depression, unusual mood changes, or thoughts of self-harm, contact your doctor or call/text 988 (Suicide & Crisis Lifeline) immediately.

Cardiac arrhythmias: In March 2021, the FDA issued a warning about the potential for cardiac arrhythmias in patients with pre-existing structural or conduction heart defects. If you have known heart disease and develop palpitations, fast or slow heartbeat, or fainting, contact your doctor.

Hemophagocytic lymphohistiocytosis (HLH): A rare but severe immune system condition causing widespread inflammation. Symptoms include prolonged fever, enlarged spleen/liver, and cytopenias.

Side Effects Specific to Certain Patient Groups

Women on hormonal contraceptives: Estrogen-containing contraceptives reduce lamotrigine blood levels by up to 50%, which may reduce seizure protection. Conversely, lamotrigine may reduce the effectiveness of hormonal contraceptives. Use a backup contraception method and discuss with your doctor.

Children: Higher rate of serious rash in pediatric patients compared to adults. The slow titration schedule is especially critical in children.

Pregnant patients: Lamotrigine levels fluctuate significantly during pregnancy (levels decrease as pregnancy progresses). Careful dose monitoring and frequent follow-up are required. Enroll in the North American Antiepileptic Drug Pregnancy Registry at 888-233-2334.

When to Seek Emergency Care

Call 911 or go to the emergency room immediately if you experience:

Blistering skin or mucous membrane sores (mouth, eyes, or genitals)

Rapidly spreading painful skin rash with peeling

A seizure that lasts more than 5 minutes or does not stop

Severe neck stiffness, high fever, and confusion (possible meningitis)

Suicidal thoughts or intent to harm yourself — call/text 988 immediately

For information on drug interactions that can worsen lamotrigine side effects, see: Lamotrigine Drug Interactions: What to Avoid and What to Tell Your Doctor.

If your side effects have led to a medication change and you need to locate a different prescription, medfinder can help you find it at a pharmacy near you.