Suicidal behavior and antiepileptic drugs in epilepsy: analysis of the emerging evidence

Abstract

Two years after the warning issued by the Food and Drug Administration on an increased risk of suicide for people taking antiepileptic drugs (AEDs), a number of pharmacoepidemiologic studies have been published but the scientific community is far from definitive answers. The present paper is aimed at reviewing available evidence on the association between AEDs and suicidal behavior, discussing major variables involved such as the relationship between epilepsy, depression, and suicide and the psychotropic potential of AEDs. All studies published so far show a lack of concordance and are constrained by various methodological limitations. What seems to be established is that mood disorders represent a frequent comorbidity in epilepsy and suicide is a serious complication more frequently encountered in epilepsy rather than in the general population. Moreover, a subgroup of patients appears to be at risk of developing treatment-emergent psychiatric adverse effects of AEDs independently of the specific mechanism of action of the drug. The prior history of suicide attempt, especially preceding the onset of the epilepsy, may represent a key element explaining why what is observed is independent of the specific mechanism of the drug. In general terms, risks associated with stopping, or not even starting, AEDs in epilepsy might well be in excess of the risk of suicide in epilepsy, as deaths due to accident and epilepsy itself may predominate. Clinicians need to pay attention not only to seizure patterns when choosing the appropriate AED but also to a number of different parameters (eg, age, gender, working needs, medical comorbidities, history of psychiatric disorders, and suicidality before epilepsy onset) and not the least the mental state of the patient. Missing severe complications such as suicidal behavior or delaying its treatment may worsen the prognosis of epilepsy.

Lamotrigine positively affects the development of psychiatric comorbidity in epileptic animals, while psychiatric comorbidity aggravates seizures

“…The choice of LTG was based on the evidence that it has a good profile in patients with epilepsy with comorbid psychiatric symptoms [70][71][72]. Lamotrigine is effective in the CMS model of depression, restoring normal behavior acting through BDNF and VEGF [73,74]; however, it was tested at a dose of 30 mg/kg for 14 days and started a week after the beginning of CMS.…”

Suicide and epilepsy: do antiepileptic drugs increase the risk?

“…It is evident that well-designed prospective studies are needed in order to clarify this point. The positive aspect of the FDA warning is that it highlighted the importance of screening for suicide in people with Cohort and case-crossover Increased risk for CLB, VPA, LTG, PB, LEV when compared to CBZ Demographic and medical factors, previous history of depression [12] Nested matched case--control Increased risk for LEV, LTG when compared to GBP Demographic and medical factors, previous history of depression* [13] Cohort Increased risk for GBP when compared to TPM/CBZ Demographics and large list of medical factors, previous history of depression z [14] Nested case--control Increased risk for LEV, VGB, TGB, TPM Type of epilepsy, use of benzodiazepines and psychiatric disorders [15] Cohort and case--control No increased risk Age, duration of illness, AED use, drugs for psychiatric disorders, psychiatric disorders, alcohol abuse and chronic disease score § [10] Cohort No increased risk Demographic and medical factors { [16] Modified from [7]. *Suicide was also considered but time frame not specified.…”

“…Limitations of the FDA meta-analysis and evidence from the literature A number of major methodological flaws of the FDA metaanalysis have been identified [7,8] and a consensus statement by an ad-hoc Task Force of the International League Against Epilepsy has been published [9]. The major limitation of the FDA meta-analysis is the lack of a systematic data collection.…”

Comments on Jones JE et al. Rates and risk factors for suicide, suicidal ideation, and suicide attempts in chronic epilepsy. Epilepsy & Behavior 2003;4(Suppl. 3):S31-38

“…The FDA data were received with great skepticism by clinicians and professional societies. Some investigators questioned the validity of FDA findings, identifying serious methodological flaws [14,15]. An expert consensus statement developed by an ad hoc Task Force of the Commission on Neuropsychobiology of the International League Against Epilepsy (ILAE) highlighted the need for screening instruments and clinical monitoring [16].…”