Misdiagnosis of lamotrigine toxicity as posterior circulation transient ischemic attack or stroke.

PURPOSE: Lamotrigine (LTG) is one of the most used antiseizure medications (ASMs). Titration is indicated for incomplete seizure control, but toxicity with vertigo, ataxia, and diplopia may ensue. Lamotrigine concentration would be the optimal diagnostic test. However, patients often receive a stroke evaluation when presenting to the emergency department (ED), leading to unnecessary cost and delayed management. We investigated the frequency of stroke evaluation for symptoms associated with LTG toxicity and attempted to identify factors leading to this expensive evaluation. METHODS: We identified adult patients treated with LTG who presented to an emergency room with dizziness, ataxia, or diplopia and received a negative stroke evaluation, between 2003 and 2018. They were among 972 patients treated with LTG for epilepsy. We collected age at time of occurrence, symptoms presented, imaging studies performed, LTG dose and serum concentration, and the time the result was available. As a denominator, we also identified patients who developed clinical LTG toxicity during the same time period. RESULTS: Thirteen patients with LTG toxicity had 16 negative stroke evaluations in the emergency room. Their mean age was 62 years (range: 43-79) as compared with 47 years for all patients treated with LTG (p < 0.0005). The mean daily LTG dose was 621 mg (range: 300-900 mg). A LTG serum concentration was requested on the day of evaluation in 7 instances, though the result was never available until at least the next day. In 4 instances, the LTG level was drawn 1-3 days after presentation. Five of the patients in this group were among 71 patients with clinical LTG toxicity and LTG concentration >20. CONCLUSION: Emergency departments will frequently call a stroke alert for patients taking LTG and presenting with symptoms consistent with LTG toxicity, particularly in seniors at greater risk of stroke. This adds not only expense but also radiation and contrast exposure from computed tomography (CT) studies. We recommend that a rapid LTG assay be made available and always ordered in patients receiving LTG, avoiding the considerable expense of an unnecessary stroke evaluation.

Conversion from immediate-release to extended-release lamotrigine improves seizure control.

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. CONCLUSION: 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.