ABSTRACT
BACKGROUND AND OBJECTIVES: A recent Food and Drug Administration warning concerning an arrhythmogenic potential of lamotrigine created concern in the neurologic community. This warning was based on in vitro studies, but no clinically relevant risk was considered. This rapid systematic review aims to elucidate the risk of lamotrigine on sudden death or ECG abnormalities. METHODS: We conducted a systematic search of Ovid Medline and Ovid Embase, including randomized controlled trials and observational studies and studies of people with or without epilepsy, with the outcome measures sudden unexpected death in epilepsy (SUDEP) or sudden cardiac death as well as the development or worsening of ECG abnormalities. We evaluated the sudden death definitions used in all included studies, as some could have used unclear or overlapping definitions. We used the American Academy of Neurology risk of bias tool to evaluate the class of evidence and the GRADE approach to evaluate our confidence in the evidence. RESULTS: We included 26 studies with 24,962 participants, of whom 2,326 used lamotrigine. Twelve studies showed no significant risk of SUDEP for lamotrigine users. One study reporting on sudden cardiac death and 3 studies with unclear sudden death definitions did not report an elevated risk of death in lamotrigine users compared to controls. In 10 studies reporting on ECG measures, there was no statistically significant increased risk among lamotrigine users except in 2 studies. These 2 studies reported either "slight increases" in PR interval or an increased PQ interval that the primary study authors believed to be related to structural cardiac differences rather than an effect of lamotrigine. One study was rated Class II; all others were Class III or IV. We had very low confidence in the evidence following the GRADE assessment. None of the studies examined the risk of lamotrigine in people with preexisting cardiac conditions. DISCUSSION: There is insufficient evidence to support or refute that lamotrigine is associated with sudden death or ECG changes in people with or without epilepsy as compared to antiseizure medication or placebo, due to the high risk of bias in most studies and low precision and inconsistency in the reported results.
Subject(s)
Anticonvulsants , Arrhythmias, Cardiac , Death, Sudden, Cardiac , Lamotrigine , Anticonvulsants/adverse effects , Arrhythmias, Cardiac/chemically induced , Death, Sudden, Cardiac/etiology , Epilepsy/drug therapy , Humans , Lamotrigine/adverse effects , Risk FactorsABSTRACT
PURPOSE: To determine the burden of non-epilepsy drugs on people with epilepsy, using administrative health care data. METHODS: The Achmea Health Insurance Database (AHID) contains health claims data from 25 % of the Dutch population. From the AHID, we selected all policyholders with coverage for at least one full calendar year between 2006-2009. We included adults with diagnostic codes for epilepsy and randomly selected two frequency-matched controls per case. We labeled drugs dispensed at least twice per calendar year as chronic and excluded antiseizure medications. We estimated and compared the prevalence of chronic medication use, number of chronic medications used, number of prescriptions dispensed, Rx Risk comorbidity index, and drug burden index (DBI) between people with epilepsy and controls. RESULTS: Non-epilepsy chronic medication use was more frequent in people with epilepsy than controls (67 % versus 59 %, p < 0.001). People with epilepsy had an increased DBI (average 0.19 versus 0.10, p < 0.001), used more chronic medications (median 2 versus 1, p < 0.001) and had more prescriptions dispensed (median 7 versus 3, p < 0.001). The DBI and number of unique chronic medications were higher among older (>60 years) than younger (<60 years) subjects in cases and controls. Non-epilepsy chronic medication use was more prevalent in people with epilepsy across all therapeutic drug classes and most comorbidities measured using the Rx Risk score. CONCLUSION: Chronic non-epilepsy medication use is more prevalent among people with epilepsy. The medication burden is higher among elderly with epilepsy and could partially explain the lower quality of life of people with epilepsy with comorbidities.
