Severe and Potentially Life-Threatening Side Effects
Serious Skin Rashes (Stevens-Johnson Syndrome and TEN)
Lamotrigine carries an FDA black box warning due to the risk of severe, life-threatening skin rashes such as Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). These conditions involve widespread blistering and peeling of the skin and mucous membranes. The risk is highest in the first 2 to 8 weeks of treatment and in children, increasing with rapid dose escalation or concurrent valproate use. Any rash should be medically evaluated immediately, as it's difficult to distinguish a benign rash from one that could become severe.
Hemophagocytic Lymphohistiocytosis (HLH)
HLH is a rare, severe immune reaction linked to lamotrigine, causing uncontrolled immune activation and inflammation. Symptoms like persistent fever, rash, enlarged organs, and blood abnormalities can be nonspecific. Lamotrigine should be stopped if HLH is suspected.
Aseptic Meningitis
Inflammation of the protective layers of the brain and spinal cord, known as aseptic meningitis, has been associated with lamotrigine. Symptoms like stiff neck, fever, and headache typically resolve upon discontinuation, but may return with re-exposure.
Multiorgan Hypersensitivity (DRESS)
Drug reaction with eosinophilia and systemic symptoms (DRESS) is another rare and serious reaction affecting multiple organs. Symptoms include fever, rash, swollen lymph nodes, and potential organ involvement, requiring prompt medical attention.
Suicidal Thoughts and Behavior
An FDA warning highlights the increased risk of suicidal thoughts and behaviors with anticonvulsants like lamotrigine. Patients and caregivers should watch for mood or behavioral changes and contact a doctor if they occur.
Cardiac Effects
Recent FDA warnings indicate a potential for increased heart rhythm problems, particularly in patients with pre-existing heart conditions, due to lamotrigine's sodium channel blocking effect. An EKG may be needed for some patients.
Common Side Effects
Many patients experience milder, common side effects that often improve with time.
- Central Nervous System (CNS) Effects: Dizziness, headache, drowsiness, insomnia, tremor, and coordination problems are common.
- Gastrointestinal (GI) Issues: Nausea, vomiting, diarrhea, and stomach pain can occur; taking with food may help.
- Ocular Effects: Blurred and double vision are common and often resolve with continued treatment.
- Other common effects: Fatigue, sore throat, and a non-serious mild rash are also possible.
Comparison of Side Effects by Indication
Clinical trials have noted some differences in commonly reported side effects between epilepsy and bipolar disorder patients.
| Feature | Common Side Effects (Epilepsy) | Common Side Effects (Bipolar Disorder) |
|---|---|---|
| Neurological | Dizziness, headache, blurred vision, double vision, coordination problems | Insomnia, excessive sleepiness, back pain, fatigue |
| Gastrointestinal | Nausea, vomiting, indigestion | Nausea, vomiting, constipation |
| Other | Flu-like symptoms, runny nose, sore throat | Dry mouth, abdominal pain, fatigue |
What to Do If You Experience Side Effects
Seek Immediate Medical Help If:
- You develop any rash, blistering, or peeling.
- You notice painful sores in your mouth or around your eyes.
- You experience swelling of your face, lips, tongue, or throat.
- You have a fever, swollen glands, or severe muscle pain.
- You develop signs of meningitis, such as a stiff neck, severe headache, and light sensitivity.
- You experience an irregular heart rate, chest pain, or shortness of breath.
- You have new or worsening mood changes or suicidal thoughts.
For Mild or Persistent Side Effects
- For dizziness or drowsiness: Avoid driving or operating heavy machinery. These often improve over time.
- For GI upset: Try taking the medication with food.
- For headaches: Stay hydrated and rest; consult your doctor before using pain relievers.
- For sleep issues: Practice good sleep hygiene and discuss timing with your doctor.
Conclusion
Lamotrigine is effective for epilepsy and bipolar disorder, but carries risks from common side effects like dizziness and nausea to rare but severe reactions including life-threatening rashes and cardiac issues. A slow dose titration, particularly with concurrent valproate, minimizes the rash risk. Prompt medical attention for any rash or unusual symptoms is vital. Patient education and cautious dosing are key to safe treatment. For more information, refer to the FDA website.
