TY - JOUR
T1 - Do antiepileptic drugs or generalized tonic-clonic seizure frequency increase SUDEP risk? A combined analysis
AU - Hesdorffer, Dale C.
AU - Tomson, Torbjorn
AU - Benn, Emma
AU - Sander, Josemir W.
AU - Nilsson, Lena
AU - Langan, Yvonne
AU - Walczak, Thaddeus S.
AU - Beghi, Ettore
AU - Brodie, Martin J.
AU - Hauser, W. Allen
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - Antiepileptic drugs
KW - Case-control study
KW - Epilepsy
KW - Generalized tonic-clonic seizures frequency
KW - SUDEP
UR - http://www.scopus.com/inward/record.url?scp=84856337692&partnerID=8YFLogxK
U2 - 10.1111/j.1528-1167.2011.03354.x
DO - 10.1111/j.1528-1167.2011.03354.x
M3 - Article
C2 - 22191685
AN - SCOPUS:84856337692
SN - 0013-9580
VL - 53
SP - 249
EP - 252
JO - Epilepsia
JF - Epilepsia
IS - 2
ER -