Temporal trends in new exposure to antiepileptic drug monotherapy and suicide-related behavior

Abstract

Objective: Because some recent studies suggest increased risk for suicide-related behavior (SRB; ideation, attempts) among those receiving antiepileptic drugs (AEDs), we examined the temporal relationship between new AED exposure and SRB in a cohort of older veterans.

Methods: We used national Veterans Health Administration databases to identify veterans aged ≥65 years who received a new AED prescription in 2004-2006. All instances of SRB were identified using ICD-9-CM codes 1 year before and after the AED exposure (index) date. We also identified comorbid conditions and medication associated with SRB in prior research. We used generalized estimating equations with a logit link to examine the association between new AED exposure and SRB during 30-day intervals during the year before and after the index date, controlling for potential confounders.

Results: In this cohort of 90,263 older veterans, the likelihood of SRB the month prior to AED exposure was significantly higher than in other time periods even after adjusting for potential confounders. Although there were 87 SRB events (74 individuals) the year before and 106 SRB events (92 individuals) after, approximately 22% (n = 16) of those also had SRB before the index date. Moreover, the rate of SRB after AED start was gradually reduced over time.

Conclusions: The temporal pattern of AED exposure and SRB suggests that, in clinical practice, the peak in SRB is prior to exposure. While speculative, the rate of gradual reduction in SRB thereafter suggests that symptoms may prompt AED prescription.

Figure 1. Temporal relationship of seizure medication index date and suicide-related behavior

Suicide-related behavior (SRB) before and after receipt of antiepileptic drugs (AEDs) among older veterans. The index date (hashed line) indicates the patient's receipt of AEDs. Values to the left of the index date show the incidence of SRB up to 12 months before receipt of AEDs. Values to the right of the index date show incidence of SRB up to 12 months after receipt of AEDs.

Figure 2. Suicide-related behavior in relation to the month before seizure medication prescription

Graphed adjusted odds ratios show the likelihood of suicide-related behavior before and after the index period (30 days prior to and including the date of first antiepileptic drug prescription); odds ratios adjusted for variables described in table 1.