Authors :
Presenting Author: Majed Alomar, MBBS – Massachusetts General Hospital - Harvard Medical School
Yekaterina Salnikova, MD – Massachusetts General Hospital
Sydney Cash, MD, PhD – Massachusetts General Hospital
Sahar Zafar, MD, MBBS – Massachusetts General Hospital
Rationale:
The use of glucagon-like peptide-1 (GLP-1) receptor agonists has markedly increased due to their effectiveness in diabetes and weight management. Interactions between GLP-1 agonists and antiseizure medications (ASMs), specifically lamotrigine, have not been previously reported in the literature. We present two cases illustrating significant lamotrigine toxicity following the initiation of GLP-1 agonist therapy, emphasizing the importance of monitoring for potential medication interactions.
Methods:
We retrospectively reviewed clinical presentations, serum lamotrigine levels, and outcomes for two patients who developed lamotrigine toxicity after starting GLP-1 agonist treatment.
Results:
Patient 1, who has a past medical history of epilepsy, tuberous sclerosis complex, stage 3a chronic kidney disease, and psychogenic nonepileptic seizures, was stable on lamotrigine extended-release (ER) 900 mg daily. Three days after initiating weekly tirzepatide 2.5 mg injections, she developed nausea, vomiting, dizziness, ataxia, confusion, choreiform movements, and slurred speech. Her lamotrigine level was markedly elevated at 22.2 mcg/ml (baseline 4.5–11.7 mcg/ml), decreasing to 16.6 mcg/ml the following day. Tirzepatide was held, leading to significant symptom improvement within 3 days and gradual improvement over 2 weeks.
Patient 2, who has a past medical history of epilepsy, was stable on lamotrigine ER 600 mg daily and initiated weekly semaglutide 0.25 mg injections. Soon after, she developed episodic symptoms of nausea, dizziness, imbalance, and diplopia that were initially mild but progressed over time. Symptoms typically occurred four days after each injection and improved over the following two days. Beginning in week 4 of semaglutide treatment, her lamotrigine levels were checked weekly during the peak of symptom severity and rose from a baseline of 10.9–14.3 mcg/ml to 16.5 mcg/ml at week 4 and 19.9 mcg/ml at week 5. Switching to lamotrigine ER 300 mg twice daily was ineffective, and her level rose to 32.4 mcg/ml at week 6. She was admitted, semaglutide was held, and lamotrigine was changed to 250 mg immediate-release twice daily, resulting in clinical improvement. She was discharged on lamotrigine ER 500 mg daily, and her level normalized to 10 mcg/ml. Semaglutide was later resumed at the reduced lamotrigine dose without recurrence of symptoms.
Neither patient had recent changes in lamotrigine dosing or significant weight changes between the initiation of GLP-1 agonist therapy and symptom onset. Both remained seizure-free during and after the toxicity episodes.
Conclusions:
These cases suggest lamotrigine toxicity secondary to an interaction with GLP-1 agonists. Although no published reports currently describe such interactions, GLP-1–induced delayed gastric emptying may result in erratic or prolonged absorption of lamotrigine, particularly in extended-release formulations that rely on consistent gastrointestinal transit. This interaction underscores the need for close monitoring of lamotrigine levels and clinical status when initiating GLP-1 agonists in patients with epilepsy, and warrants further investigation.
Funding: None