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... Show moreBackground 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. Show less
Epidemiological estimates indicate that individuals with epilepsy are more likely to experience headaches, including migraine, than individuals without epilepsy. Headaches can be temporally... Show moreEpidemiological estimates indicate that individuals with epilepsy are more likely to experience headaches, including migraine, than individuals without epilepsy. Headaches can be temporally unrelated to seizures, or can occur before, during or after an episode; seizures and migraine attacks are mostly not temporally linked. The pathophysiological links between headaches (including migraine) and epilepsy are complex and have not yet been fully elucidated. Correct diagnoses and appropriate treatment of headaches in individuals with epilepsy is essential, as headaches can contribute substantially to disease burden. Here, we review the insights that have been made into the associations between headache and epilepsy over the past 5 years, including information on the pathophysiological mechanisms and genetic variants that link the two disorders. We also discuss the current best practice for the management of headaches co-occurring with epilepsy and highlight future challenges for this area of research. Show less
The comorbidities of epilepsy include those conditions, somatic and psychiatric, that are associated with epilepsy. These associations with epilepsy may be direct and indirect, causal and spurious.... Show moreThe comorbidities of epilepsy include those conditions, somatic and psychiatric, that are associated with epilepsy. These associations with epilepsy may be direct and indirect, causal and spurious. The comorbidities of epilepsy are relevant in that they provide an opportunity to improve our understanding of the pathophysiology of epilepsy, as well as allow us to better understand factors determinant of outcome. This PhD thesis examines the comorbidities of epilepsy, as a general construct, delving into particular examples, and finally demonstrating its impact on premature mortality in epilepsy. Show less
