Neuropsychiatric Symptoms of Epilepsy

2 Depression
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are more likely to be identified in patients susceptible to develop psychiatric disorders,
such as those with a past psychiatric history or with a family psychiatric history
[ 50 ]. Accordingly, obtaining a good personal (current and past) and family
psychiatric history is of the essence to identify patients that may be at risk of developing
iatrogenic depressive episodes.
The addition of AEDs with mood-stabilizing properties, such as carbamazepine,
valproic acid, and lamotrigine, can occasionally cause depressive episodes, albeit
with a significantly lower frequency than other AEDs. More often than not, these
AEDs are associated with the occurrence of depression upon their discontinuation
in patients with a prior history of depression or panic disorder, which had been kept
in remission by these AEDs [ 51 ].
The Food and Drug Administration (FDA) announced in 2008 that it would
require manufacturers of AEDs to add a warning to their labeling indicating that the
use of these drugs increases the risk by a twofold of suicidal thoughts and behaviors
[ 52 ]. The decision was based on an FDA meta-analysis of 199 clinical multicenterrandomized,
double-blind placebo-controlled and parallel trials of 11 AEDs. The
FDA data were carefully reviewed by a task force of the American Epilepsy Society,
which identified several methodological flaws including: (1) grouping of all AEDs
(which have different mechanisms of action) into one class; (2) basing the recommendation
on spontaneously reported adverse events, rather than on systematically
acquired data [ 53 ]. Furthermore, attempts to replicate the data from the FDA metaanalysis
in five large studies yielded contradictory findings. Thus, it is possible that
certain but not every AED can cause psychiatric adverse events that can lead to
suicidal ideation and behavior, but this is likely to occur in patients with a predisposition
for psychiatric illness. Accordingly, before starting an AED, like topiramate,
zonisamide, vigabatrin, barbiturates, or levetiracetam, it is essential to inquire about
a prior personal or psychiatric history.
Depression Following Epilepsy Surgery
It is not unusual to see “mood lability” within the initial 6 weeks to 3 months after
surgery. Often, these symptoms subside, but in up to 30 % of patients, major depressive
episodes may become apparent within the first 6 months [ 54 ]. Characteristically,
symptoms vary from mild to very severe, including suicidal attempts. In most
instances, these depressive disorders respond readily to pharmacologic treatment
with antidepressant drugs (see below).
Patients with a prior history of depression are at greater risk. A German study
found that patients with personality disorders are at higher risk of suffering from
postoperative psychiatric complications, as compared with patients with other preoperative
psychiatric conditions (such as depression) or with patients with no preoperative
psychiatric diagnosis whatsoever [ 55 ]. While some studies have not found
a relation between depression and the postsurgical control of seizures, others have
[ 54 ]. All patients undergoing epilepsy surgery, therefore, should be advised of this
potential complication, prior to surgery .