Relationship between antiepileptic drugs and suicide attempts in patients with bipolar disorder

Abstract

Context: On January 31, 2008, the Food and Drug Administration issued an alert regarding increased risk of suicidal thoughts and behavior related to use of antiepileptic drugs (AEDs). On July 10, 2008, a Food and Drug Administration scientific advisory committee voted that, yes, there was a significant positive association between AEDs and suicidality but voted against placing a black box warning on AEDs for suicidality.

Objective: To determine if AEDs increase the risk of suicide attempt in patients with bipolar disorder.

Design: A pharmacoepidemiologic study in which suicide attempt rates were compared before and after treatment and with a medication-free control group. Analyses were restricted to AED and lithium monotherapy.

Setting: We used the PharMetrics medical claims database to study the relationship between the 11 AEDs identified in the FDA alert, and lithium, to suicide attempts.

Main outcome measure: Suicide attempts. Patients A cohort of 47 918 patients with bipolar disorder with a minimum 1-year window of information before and after the index date of their illness.

Results: Overall, there was no significant difference in suicide attempt rates for patients treated with an AED (13 per 1000 person-years [PY]) vs patients not treated with an AED or lithium (13 per 1000 PY). In AED-treated subjects, the rate of suicide attempts was significantly higher before treatment (72 per 1000 PY) than after (13 per 1000 PY). In patients receiving no concomitant treatment with an antidepressant, other AED, or antipsychotic, AEDs were significantly protective relative to no pharmacologic treatment (3 per 1000 vs 15 per 1000 PY).

Conclusions: Despite Food and Drug Administration reports regarding increased risk of suicidality associated with AED treatment, the current study reveals that, as a class, AEDs do not increase risk of suicide attempts in patients with bipolar disorder relative to patients not treated with an AED or lithium. Use of AEDs reduces suicide attempt rates both relative to patients not receiving any psychotropic medication and relative to their pretreatment levels.

Figure 1

Suicide attempt rates before and after treatment by treatment type. AED indicates antiepileptic drug.

Figure 2

Hazard functions for suicide rates over time. Comparisons of patients treated with an antiepileptic drug (AED) vs patients not treated with an AED were adjusted for age, sex, concomitant treatment, previous suicide attempt, and year.