Adding lamotrigine to valproate: Incidence of rash and other adverse effects

Purpose: Valproate (VPA) triples the half-life of lamotrigine (LTG), and co mbined use may be difficult. The adverse effect (AE) profile of this combin ation needs clarification. Methods: We prospectively recorded our experience in adding LTG to VPA-cont aining regimens in 108 patients. Data collected included medications, seizu re types and syndromes, and AEs. Patients were followed up to 27 months, un til a stable dose was reached, or until LTG was discontinued. Patient manag ement was not altered by this study. There were 60 patients with partial-on set seizures, 30 with generalized onset, and 12 with the Lennox-Gastaut syn drome. In 37, LTG was added to VPA monotherapy, and in 71, to VPA and other drugs. The median starting dose of LTG in our adult patients was 20.8 mg/d ay. Results: LTG was added successfully in 86 (80%) patients. It was discontinu ed in 22 (20%): seven because of rash, seven for other AEs, and nine for ot her reasons. Rash occurred in 14 (13%) but caused discontinuation of LTG in only seven. We found a rash rate of 14.2% and a discontinuation rate becau se of rash of 8.7% among 310 patients in whom LTG was added to drug regimen s not including VPA. Other AEs included fatigue (12%), gastrointestinal (GI ) symptoms (9%), dizziness, headache, and insomnia (3% each). Serious AEs w ere hallucinations (two patients), hepatic enzyme elevations (two patients) , irritability (one patient), and low white blood cell count (one patient). Whether LTG was added to VPA monotherapy or polytherapy made no difference in overall AE rate. Conclusions: LTG can be added to VPA with an acceptable incidence of side e ffects. LTG-induced rashes are no more common with VPA than with other drug s when LTG is added at very low initial dosages. Rashes are potentially ser ious and should be evaluated promptly.