Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death.

Area of Science:

• Pharmacovigilance
• Clinical Epidemiology
• Neuroscience

Background:

• US FDA mandated warning labels for anticonvulsants in 2008 due to increased suicidal ideation and behavior risk.
• Previous meta-analyses were insufficient to assess risks associated with individual anticonvulsant drugs.

Purpose of the Study:

• To evaluate the risk of suicidal acts and combined suicidal acts or violent death linked to individual anticonvulsant medications.
• To compare these risks against reference anticonvulsant drugs.

Main Methods:

• A cohort study design was employed using the HealthCore Integrated Research Database (HIRD).
• Patients aged 15 and older initiating anticonvulsant therapy between July 2001 and December 2006 were analyzed.
• Cox proportional hazards models and propensity score-matched analyses controlled for comorbidities and risk factors, comparing individual anticonvulsants to topiramate and carbamazepine.

Main Results:

• The study analyzed 297,620 treatment episodes, identifying 26 completed suicides, 801 attempted suicides, and 41 violent deaths.
• Increased risk of suicidal acts was observed for gabapentin (HR, 1.42), lamotrigine (HR, 1.84), oxcarbazepine (HR, 2.07), tiagabine (HR, 2.41), and valproate (HR, 1.65) compared to topiramate.
• Gabapentin showed increased risk in younger/older patients, those with mood disorders, or epilepsy/seizures when compared to carbamazepine.

Conclusions:

• Gabapentin, lamotrigine, oxcarbazepine, and tiagabine may be associated with an increased risk of suicidal acts or violent deaths.
• These findings highlight the importance of individualized risk assessment for anticonvulsant therapy.