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Antiepileptic Medications and the Risk of Suicide

Aidan Neligan, MSc, MRCP; Gail S. Bell, MD; Marco Mula, MD, PhD
JAMA. 2010;304(5):521-523. doi:10.1001/jama.2010.1067
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To the Editor: Dr Patorno and colleagues1 studied antiepileptic drugs (AEDs) and the risk of suicide, reporting an increased risk of suicide attempts, completed suicide, or violent death in people taking gabapentin, lamotrigine, oxcarbazepine, tiagabine, and valproate, compared with topiramate. In extrapolating these findings to people with epilepsy, several points need to be borne in mind.

First, only a small proportion of the cohort was taking AEDs for epilepsy. Second, the cohort had significant comorbidities, with on average more than 40% taking antidepressants or analgesics. Third, rates were compared with people taking topiramate (for the whole cohort) and with people taking carbamazepine (for people with epilepsy) rather than with the general population.

Fourth, the median follow-up was 60 days. No indication is given where (or why) the medication was started. It is possible that for some individuals it was for the treatment of an acute mood episode of a bipolar disorder, and the high suicide rate may reflect this. Almost all the AEDs reported to be associated with increased risk are also used as mood stabilizers.

Fifth, the study is limited by the lack of pretreatment data. Sixth, a high-dimensional propensity score analysis was carried out due to potential confounding factors like depression. In this analysis, only gabapentin, oxcarbazepine, and tiagabine were associated with a significant risk.

Persons with epilepsy have a 3-fold increased risk of suicide compared with the general population,2 with the highest risk in those with comorbid psychiatric conditions.3 Whether or to what extent AEDs contribute to this risk has been a controversial topic since the US Food and Drug Administration issued an alert on the risk of suicide in people taking AEDs.4 Potential issues surrounding this warning have since been debated.5

Although the study by Patorno et al is of interest, further large studies are needed to determine such risk when epilepsy is the primary indication for the medication.

AUTHOR INFORMATION

Financial Disclosures: Dr Neligan reported receiving travel grants and an honorarium from Eisai. Dr Bell reported that her husband is employed by, and owns shares in, GlaxoSmithKline, the manufacturer of Lamictal. Dr Mula reported that he has received travel grants or consultancy fees from pharmaceutical companies involved in the manufacture of AEDs, including Novartis, Pfizer, UCB Pharma, Eisai, Schwarz Pharma, Janssen-Cilag, Sanofi-Aventis, and GlaxoSmithKline.

REFERENCES

Patorno E, Bohn RL, Wahl PM,  et al.  Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death [published correction appears in JAMA. 2010;303(22):2252].  JAMA. 2010;303(14):1401-1409
PubMedCrossRef
Bell GS, Gaitatzis A, Bell CL, Johnson AL, Sander JW. Suicide in people with epilepsy: how great is the risk?  Epilepsia. 2009;50(8):1933-1942
PubMedCrossRef
Christensen J, Vestergaard M, Mortensen PB, Sidenius P, Agerbo E. Epilepsy and risk of suicide: a population-based case-control study.  Lancet Neurol. 2007;6(8):693-698
PubMedCrossRef
 Statistical review and evaluation: antiepileptic drugs and suicidality [May 2008]. US Food and Drug Administration Web site. http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4372b1-01-FDA.pdf. Accessed April 21, 2010
Hesdorffer DC, Kanner AM. The FDA alert on suicidality and antiepileptic drugs: fire or false alarm?  Epilepsia. 2009;50(5):978-986
PubMedCrossRef

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Patorno E, Bohn RL, Wahl PM,  et al.  Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death [published correction appears in JAMA. 2010;303(22):2252].  JAMA. 2010;303(14):1401-1409
PubMedCrossRef
Bell GS, Gaitatzis A, Bell CL, Johnson AL, Sander JW. Suicide in people with epilepsy: how great is the risk?  Epilepsia. 2009;50(8):1933-1942
PubMedCrossRef
Christensen J, Vestergaard M, Mortensen PB, Sidenius P, Agerbo E. Epilepsy and risk of suicide: a population-based case-control study.  Lancet Neurol. 2007;6(8):693-698
PubMedCrossRef
 Statistical review and evaluation: antiepileptic drugs and suicidality [May 2008]. US Food and Drug Administration Web site. http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4372b1-01-FDA.pdf. Accessed April 21, 2010
Hesdorffer DC, Kanner AM. The FDA alert on suicidality and antiepileptic drugs: fire or false alarm?  Epilepsia. 2009;50(5):978-986
PubMedCrossRef
August 4, 2010
Elisabetta Patorno, MD, MPH; Jerry Avorn, MD; Sebastian Schneeweiss, MD, ScD
JAMA. 2010;304(5):521-523.
August 4, 2010
Robert D. Gibbons, PhD; Bruce L. Lambert, PhD; J. John Mann, MD
JAMA. 2010;304(5):521-523.
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