Antiepileptic drugs and suicidality

Abstract

The risk of suicide in patients with epilepsy is significantly higher than the general population. There are many hypotheses as to the reasons for this, but the potential role of anti-epileptic drugs (AEDs) in increasing suicidality has recently been brought into question. In 2008, the U.S. Food and Drug Administration (FDA) published a warning after a meta-analysis of data from all clinical trials involving AEDs found a suicidality risk of 0.43 per 1000 patients in active drug arms of these clinical trials compared to a rate in the placebo arm of 0.22. While an increased risk for individual AEDs was found in two, the FDA decided to issue a warning for the entire AED class. While this decision and the meta-analysis findings have been considered controversial, and have created concern that this stated risk may dissuade use of AEDs by patients who would benefit from them, it has led to increased awareness of the risk of suicidality and psychiatric co-morbidity in this patient group. In this article, the association of epilepsy and AEDs with psychiatric disease and suicidality are reviewed, perspective as to the significance and limitations of the FDA’s findings are discussed, and some options for suicidality screening and their potential utility in clinical care are evaluated.

A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures

“…Patients with epilepsy are also known to be at increased risk of psychiatric-related disorders [33][34][35]. Several AEDs have known psychiatric and behavioral side effects in patients with epilepsy, possibly representing a drug class effect [44,[46][47][48][49][50][51][52][53].…”

“…Psychiatric conditions exist at a higher prevalence among patients with epilepsy than in the general population, including depression, anxiety, and aggression disorders [33,34]. Some AEDs have shown potential associations with psychiatric AEs and behavioral changes [35][36][37]. Psychiatric-related AEs (such as depression) are commonly listed in AED labeling, including that for lacosamide [1,2].…”

“…AEDs in general may increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. A class warning is in place and acknowledged in all AED product labeling [35,[38][39][40]; however, the mechanism for this increased risk is unknown. The overall efficacy and safety of adjunctive lacosamide use for the treatment of uncontrolled POS was established in well-controlled clinical studies.…”

Risk factors for postoperative depression: A retrospective analysis of 248 subjects operated on for drug‐resistant epilepsy

“…With respect to suicidal risk in epileptic patients on therapy with AEDs, Britton and Shih suggested that LEV and topiramate are related to a higher suicidal risk compared to other AEDs, whereas VPA and CBZ could have a protective effect.…”

Antiepileptic Drugs and Suicide: A Systematic Review of Adverse Effects

“…Since the publication of the FDA alert on the risk of suicide associated with 11 AEDs, several observational studies [27,28], as well as reviews and expert opinions [29,30,31,32], have attempted to disentangle this controversial relationship. We ultimately reviewed 11 studies that reported findings on the effects of AEDs on suicide compared to a placebo or no treatment; 3 studies [2,17,21] reported a 2- to 4-fold overall increased risk of suicide with AEDs as a group.…”