Antiepileptic drugs and risk of suicide: a nationwide study

TY - JOUR

T1 - Antiepileptic drugs and risk of suicide: a nationwide study

AU - Olesen, J.B.

AU - Hansen, Peter Riis

AU - Erdal, Jesper

AU - Abildstrøm, Steen Zabell

AU - Weeke, Peter

AU - Fosbol, E.L.

AU - Poulsen, Henrik Enghusen

AU - Gislason, Gunnar H

AU - Olesen, Jonas Bjerring

AU - Fosbøl, Emil Loldrup

N1 - (c) 2010 John Wiley & Sons, Ltd.

PY - 2010/5

Y1 - 2010/5

N2 - Purpose: Patients with epilepsy or psychiatric diseases have increased risk of suicide, but whether the risk is influenced by antiepileptic drug (AED) treatment is unclear. Studies have suggested that AEDs in general increase the risk of suicidal behaviour shortly after initiation. This study investigated possible differences in suicide risk associated with different AEDs. Methods: The use of AEDs in the Danish population from 1997 to 2006 was determined by prescription claims. The risk of suicide associated with use of AEDs was estimated by case-crossover analyses, where each case serves at its own control during different periods. For sensitivity, the risk of suicide was estimated by a time-dependent Cox proportional-hazard analysis in AED treatment-naïve patients. Results: Therewere 6780 casescommitting suicide in the 10-year study period, ofwhich 422 receivedAEDtreatment at the time of suicide. The case-crossover analysis estimated AED treatment initiation to increase the risk of suicide (odds ratio (OR): 1.84, 95% confidence interval (CI): 1.36-2.49). Clonazepam(OR: 2.01, CI: 1.25-3.25), valproate(OR: 2.08, CI: 1.04-4.16), lamotrigine (OR: 3.15,CI: 1.35-7.34) and phenobarbital (OR: 1.96,CI: 1.02-3.75)were associatedwith a significant increased risk, while the remaining examinedAEDs did not significantly influence the risk. In the cohort comprising of 169 725 AED treatment-naïve patients, the Cox proportional-hazard analysis yielded similar results. Conclusions: This study suggests that clonazepam, valproate, lamotrigine and phenobarbital relatively shortly after treatment initiation may increase the risk of suicide. The increased risk of suicide associated with these AEDs appears to be a consistent finding.

AB - Purpose: Patients with epilepsy or psychiatric diseases have increased risk of suicide, but whether the risk is influenced by antiepileptic drug (AED) treatment is unclear. Studies have suggested that AEDs in general increase the risk of suicidal behaviour shortly after initiation. This study investigated possible differences in suicide risk associated with different AEDs. Methods: The use of AEDs in the Danish population from 1997 to 2006 was determined by prescription claims. The risk of suicide associated with use of AEDs was estimated by case-crossover analyses, where each case serves at its own control during different periods. For sensitivity, the risk of suicide was estimated by a time-dependent Cox proportional-hazard analysis in AED treatment-naïve patients. Results: Therewere 6780 casescommitting suicide in the 10-year study period, ofwhich 422 receivedAEDtreatment at the time of suicide. The case-crossover analysis estimated AED treatment initiation to increase the risk of suicide (odds ratio (OR): 1.84, 95% confidence interval (CI): 1.36-2.49). Clonazepam(OR: 2.01, CI: 1.25-3.25), valproate(OR: 2.08, CI: 1.04-4.16), lamotrigine (OR: 3.15,CI: 1.35-7.34) and phenobarbital (OR: 1.96,CI: 1.02-3.75)were associatedwith a significant increased risk, while the remaining examinedAEDs did not significantly influence the risk. In the cohort comprising of 169 725 AED treatment-naïve patients, the Cox proportional-hazard analysis yielded similar results. Conclusions: This study suggests that clonazepam, valproate, lamotrigine and phenobarbital relatively shortly after treatment initiation may increase the risk of suicide. The increased risk of suicide associated with these AEDs appears to be a consistent finding.

U2 - 10.1002/pds.1932

DO - 10.1002/pds.1932

M3 - Journal article

SN - 1053-8569

VL - 19

SP - 518

EP - 524

JO - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

IS - 5

ER -