Do antiepileptic drugs or generalized tonic-clonic seizure frequency increase SUDEP risk? A combined analysis

• Published in: Epilepsia (Copenhagen) Vol. 53; no. 2; pp. 249 - 252
• Main Authors: Hesdorffer, Dale C., Tomson, Torbjorn, Benn, Emma, Sander, Josemir W., Nilsson, Lena, Langan, Yvonne, Walczak, Thaddeus S., Beghi, Ettore, Brodie, Martin J., Hauser, W. Allen
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2012; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: Anticonvulsants - adverse effects; Anticonvulsants. Antiepileptics. Antiparkinson agents; Antiepileptic agents; Antiepileptic drugs; Biological and medical sciences; Carbamazepine; Case-Control Studies; Case-control study; Data processing; Death, Sudden - etiology; Epilepsy; Epilepsy - complications; Epilepsy - drug therapy; Epilepsy - epidemiology; Generalized tonic-clonic seizures frequency; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; lamotrigine; Medical sciences; Medicin och hälsovetenskap; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Pharmacology. Drug treatments; Phenytoin; Regression analysis; Risk Factors; Seizures; Seizures - complications; Seizures - drug therapy; Studies; SUDEP; Valproic acid; Nervous system diseases; Epilepsy; Case-control study; Anticonvulsant; Case control study; Generalized tonic-clonic seizures frequency; Cerebral disorder; Convulsion; SUDEP; Central nervous system disease; Risk factor; Neurological disorder; Antiepileptic drugs
• ISSN: 0013-9580; 1528-1167; 1528-1167
• DOI: 10.1111/j.1528-1167.2011.03354.x

Summary Purpose:  In an analysis of four case–control studies of sudden unexpected death in epilepsy (SUDEP), we found that yearly frequency of generalized tonic–clonic seizures (GTCS) and antiepileptic drug (AED) polytherapy were associated with an increased risk for SUDEP. The prior analysis, however, did not evaluate AEDs and GTCS frequency concurrently. Methods:  We combined data from the three case–control studies with information on the frequency of GTCS and AED therapy, that is, carbamazepine, phenytoin, valproic acid, and other AED therapy. Number of AEDs was also considered. Lamotrigine and GTCS frequency were considered separately in two of the case–control studies. Logistic regression analysis was used to evaluate GTCS frequency, each of the AEDs, and number of AEDs. Adjusted analysis of the different AEDs accounted for study, age at death, gender, and GTCS frequency. Key Findings:  In crude analysis, GTCS frequency, AED polytherapy, and number of AEDs were associated with an increased risk for SUDEP. Analysis of individual AEDs and of number of AEDs, adjusting for GTCS frequency, revealed no increased risk associated with AEDs as monotherapy, polytherapy, or total number. GTCS frequency remained strongly associated with an increased risk for SUDEP. Significance:  Our findings—that none of the AEDs considered were associated with increased SUDEP risk as monotherapy or as polytherapy when GTCS frequency was taken into account—provide a consistent message that number of GTCS increases SUDEP risk and not AEDs. These results suggest that prevention of SUDEP must involve increased efforts to decrease GTCS frequency in order to avert the occurrence of this devastating epilepsy outcome.