Aggression in Epilepsy
A recent review provides a useful and comprehensive overview of aggressive behaviors in epilepsy. Aggression, which occurs in a minority of patients with epilepsy, is most often postictal; it does occur interictal but is rare during seizure and has not been reported preictal.
Importantly, it can be treatment-related: an increased risk of aggressive behaviors has been associated with perampanel, topiramate, and levetiracetam, with problematic aggression reported by ~50% of epilepsy patients treated with levetiracetam vs. 9% of controls in one survey (Wieshmann and Baker, 2013).
Why is it that some patients treated for epilepsy are at increased risk for aggressive behaviors? There is overlap both in the brain regions affected (temporal lobe, hippocampus, amygdala, frontal lobe, hypothalamus) and the pharmacologic targets (most commonly GABA and glutamate) for epilepsy and aggression; however, the same pharmacological targets can lead to opposing effects for each condition, perhaps due to underlying alterations in these systems within epilepsy. For example, the morphology and distribution of GABA-A receptors are altered in temporal lobe epilepsy. GABA-ergic agents, which can decrease aggression in patients without epilepsy, may have the opposite effect in patients with temporal lobe epilepsy due to these alterations in GABA-A receptors. Glutamatergic agents may have a dose-response curve in terms of their antiaggressive and antiepileptic effects, such that at low doses they may be antiepileptic but pro-aggressive, while at high doses they may be antiaggressive but pro-epileptic; this has been shown with the N-methyl-d-aspartate (NMDA) receptor antagonist phencyclidine (PCP). Consistent with this, improvement in seizures is often associated with worsening of psychotic aggression.
Unfortunately, there is very little evidence to help guide risk assessment; however, a psychiatric history, including propensity for aggressive behavior, should be obtained. Although not contraindicated, the agents with the strongest evidence for risk of aggressive behaviors (levetiracetam, perampanel, topiramate), should be used with caution in patients with psychiatric comorbidities and/or a history of aggressive behavior.
>> Brodie MJ et al. Pharmacological Rev 2016;68:563-602.
Psychosis
Researchers have identified risk factors that may help recognize patients who develop psychosis linked to their antiepileptic drug treatment. Misdiagnosing psychosis that results from an adverse reaction to antiepileptic drugs can lead to inappropriate prescribing of antipsychotic drugs. The study included 2,630 patients with epilepsy, of whom 98 (3.7%) were found to have psychotic disorders. Antiepileptic drug-induced psychotic disorder (AIPD) was identified in 14 of the 98 (14.3%) of patients with psychosis. Results show that females appear to be at a higher risk than males for AIPD, with 76.9% of AIPD patients being female compared to only 41.7% patients in the non-AIPD group. Patients with AIPD were also more likely to have temporal lobe seizures compared to the non-AIPD patients (69.2% vs 38.1%; P < .05). The antiepileptic drug levetiracetam was most commonly associated with AIPD, while carbamazepine was found to be negatively associated with AIPD.
>> Chen Z et al. Brain. 2016;DOI: https://dx.doi.org/10.1093/brain/aww196.