Neuropsychiatric Symptoms of Epilepsy

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A.M. Kanner and R. Ribot
symptoms include feelings of anhedonia, guilt, and suicidal ideation. Such mood
changes are typically brief, stereotypical, occur out of context, and are associated
with other ictal phenomena. More typically, however, ictal symptoms of depression
are followed by an alteration of consciousness, as the ictus evolves from a focal
seizure without loss of consciousness to a seizure with loss of consciousness.
Postictal symptoms of depression and depressive episodes have been recognized
for decades, but have been investigated in a systematic manner in only one study
[ 40 ]. Postictal symptoms of depression were identified in 43 of 100 consecutive
patients with refractory partial seizure disorders. These symptoms occurred after in
more than 50 % of seizures, and their duration ranged from 0.5 to 108 h, with a
median duration of 24 h. However, postictal symptoms of depression can outlast the
ictus for up to 2 weeks.
Of note, PWE may experience interictal depressive episodes with postictal exacerbation
in severity of these symptoms [ 40 ]. Furthermore, in patients with interictal
depressive episodes in remission, postictal symptoms of depression can occur
despite the presence of adequate doses of antidepressant medication (Kanner AM,
unpublished data). This observation suggests a different pathogenic mechanism
operant in postictal and interictal depressive symptoms.
Depressive Episodes as an Expression of a Para-Ictal Disorder
The sudden remission of epileptic seizures in patients with treatment-resistant epilepsy
can be followed by the occurrence of psychopathology presenting as a MDE or a psychotic
episode. This phenomenon has been known as “forced normalization” [ 41 ],
because the EEG recordings of these patients failed to reveal any epileptiform activity
concurrent with the psychopathology. In later years, this phenomenon was referred as
“alternating psychopathology” [ 42 ]. While this phenomenon is more often identified
in the setting of a psychotic episode, depressive episodes are more frequent but often
go unrecognized. Remission and/or improvement of psychiatric symptoms follow the
recurrence of seizures, though symptomatic treatment can at times be effective.
Depressive Episodes as an Iatrogenic Effect
Caused by Antiepileptic Drugs
All antiepileptic drugs (AEDs) can potentially cause psychiatric symptoms, particularly
when used at high doses [ 43 ]. However, AEDs with GABAergic properties,
primarily phenobarbital, primidone, the benzodiazepines, tiagabine, and vigabatrin,
are more likely to cause depression [ 44 – 47 ]. Other AEDs that have been associated
with the development of depression include felbamate, topiramate, levetiracetam,
zonisamide and more recently perampanel [ 7 , 48 , 49 ]. Psychiatric adverse events