title: Conversion from immediate-release to extended-release lamotrigine improves seizure control.
abstract: BACKGROUND
  Immediate release lamotrigine (LTG-IR) dosing can be limited by peak toxicity. It is thought that peak levels are responsible for some adverse effects such as dizziness, blurred vision, double vision and unsteadiness. At the same time, trough levels may be associated with reduced seizure threshold. The use of extended release lamotrigine (LTG-XR) to replace LTG-IR will be associated with less fluctuation in drug levels-lower peak levels may reduce adverse effects and higher trough levels may improve seizure control. This hypothesis was tested by analyzing seizure control and adverse effects before and after conversion from LTG-IR to LTG-XR in patients who underwent such conversion in 2009-2011.
  
  
  METHODS
  We searched our patient database to identify patients converted from LTG-IR to LTG-XR for persistent seizures or adverse effects from August 2009 until December 31, 2011. We included only patients who took LTG-IR and LTG-XR for at least 6 months each. We excluded patients with nonepileptic seizures, progressive cause of epilepsy, or not keeping a seizure record. We collected the following parameters: age at conversion, LTG-IR dose and dosing schedule, duration on that dose, LTG-XR dose and dosing schedule, LTG serum level before and after conversion, duration of LTG-XR treatment, seizure frequency before and after conversion, and change in adverse experience profile. We also recorded baseline AEDs and any AED change during the course of the analysis.
  
  
  RESULTS
  Fifty five patients (26 female) satisfied the inclusion/exclusion criteria. Their mean age was 45 years (range 23 to 86). Ten were on LTG-IR monotherapy, 24 took LTG-IR plus one other AED, most commonly levetiracetam, and the remaining 21 took LTG-IR plus at least 2 other AEDs. The mean LTG-IR dose was 544 mg/day (range 150-1100 mg/day). The mean LTG-IR serum level was 11.6 (available in 53 patients-range 4.6-21 mcg/ml). Twenty six patients were converted to the same dose and one patient took a mixture of LTG-XR and LTG-IR at the same total daily dose, while 21 had their dose slightly increased and 7 had their dose slightly decreased due to adverse effects. The mean serum level after conversion was 11.8 (available in 49 patients-range 2.6-21.2 mcg/ml). As a result of the conversion, 26 patients (47%) experienced >50% reduction in seizure frequency. There was a 46% median reduction in seizure frequency overall. Seven patients reported improvement in adverse effects.
  
  
  CONCLUSIONS
  A conversion from LTG-IR to LTG-XR can help improve seizure control in some individuals with drug-resistant epilepsy, in addition to improving tolerability. While it is indicated in individuals experiencing peak adverse effects, it should also be considered in patients who have received incomplete seizure control from LTG-IR.
authors.affiliation: A-0118 MCN, Department of Neurology, Vanderbilt University, A-0118 MCN, Nashville 37232, TN, USA. Electronic address: pat.ramey@vanderbilt.edu.
authors.forename: Patsy
authors.initials: P
authors.lastname: Ramey
authors.affiliation: A-0118 MCN, Department of Neurology, Vanderbilt University, A-0118 MCN, Nashville 37232, TN, USA. Electronic address: Melissa.osborn@vanderbilt.edu.
authors.forename: Melissa
authors.initials: M
authors.lastname: Osborn
authors.affiliation: A-0118 MCN, Department of Neurology, Vanderbilt University, A-0118 MCN, Nashville 37232, TN, USA. Electronic address: bassel.abou-khalil@vanderbilt.edu.
authors.forename: Bassel
authors.initials: B
authors.lastname: Abou-Khalil
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012640:Seizures / Q000097:blood / Q000188:drug therapy*; D018709:Statistics, Nonparametric; D013997:Time Factors; D014227:Triazines / Q000097:blood / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine
keywords: Drug-resistance; Epilepsy; Extended-release lamotrigine; Immediate-release lamotrigine; Seizure frequency; Toxicity