Lamotrigine-Induced Neutropenia Following Two Attempts to Increase Dosage Above 50 mg/day with Recovery Between Episodes Olivier Lambert, Gwenaëlle Veyrac, Christophe Armand, Sandra Bourlon, Michel Bourin and Pascale Jolliet Centre Régional de Pharmacovigilance, Institut de Biologie, Nantes, France CASE REPORT Adv Drug React Toxicol Rev 2002; 21 (3): 157-159 0964-198X/02/0003-0157/$25.00/0 © Adis International Limited. All rights reserved. Lamotrigine is a triazinic compound, chemi- cally different from the other anticonvulsants. It exerts its anticonvulsant effects by blocking volt- age-dependent sodium channels and stabilising the neuronal membranes and inhibiting the release of excitory neurotransmitters, mainly the glutamate. Lamotrigine could be associated with haemato- logical effects such as leucopenia, neutropenia, thrombocytopenia, anaemia, pancytopenia and very rarely aplastic anaemia or agranulocytosis. We re- port the case of a 76-year-old woman, who pre- sented with neutropenia induced by lamotrigine. Case Report Mrs V is 76 years old. Her past medical history consisted of an essential epilepsy since the age of 10 years, iodine and insect bite allergies, gastro- oesophageal reflux due to hiatal hernia and, her surgical history involved insertion of left hip pros- thesis, carpal tunnel surgery, appendectomy, hys- terectomy and sigmoidectomy for diverticular dis- ease. She has been receiving lamotrigine for her epilepsy since July 7, 2001, in place of a previous treatment of valproic acid (sodium valproate) which was interrupted because of bodyweight decrease (8kg loss). In August 2001, after a seizure episode, lamotrigine was gradually increased to 150 mg/day by September 20. On October 6, 2001, she was hospitalised for asthenia. Her treatment was then: phenobarbital (phenobarbitone) 150mg in the evening, clobazam 10mg three times daily, omeprazole 20mg and lam- otrigine 150mg in the evening. During this hosp- italisation, a neutropenia of 660/mm 3 and 2380 leucocytes/mm 3 was discovered, while erythro- cytes and platelets were normal. Because of the discovery of neutropenia, the dosage of lamotrig- ine was reduced to 50 mg/day, followed by a fast recovery of white cell count. On October 10, her blood count showed a leucocyte count of 2960/mm 3 with a neutrophil polynucleosis of 1570/mm 3 . The increase of white blood cells allowed Mrs V to re- turn home. The following day, Mrs V was again admitted to hospital because of thoracic pains associated with dyspnoea. During this hospitalisation, the lamotrigine dosage was again increased to 62.5 mg/day. The blood count on October 15 showed 3670 neutrophils/mm 3 and 5040 leucocytes/mm 3 . On October 17, the dosage of lamotrigine was raised to 75 mg/day, but the next day, the blood count showed a decline of white blood cells to 3120/mm 3 and 900 neutrophils/mm 3 . Lamotrigine was then definitively stopped on October 19. On October 22, a leucocyte count recovery was observed with 3350 leucocytes/mm 3 and 1000 neutrophils/mm 3 . Lamotrigine was replaced by gabapentin 600mg,