There are special considerations in pharmacologic intervention for patients with developmental disorders, mental illness, and epilepsy. Before administering a psychotropic drug to a patient with epilepsy, one must consider whether the psychiatric manifestations can be ascribed to the seizures themselves.

By separating the seizure into intervals, psychiatric manifestations attributable to seizure activity can be recognized. These intervals are:

  • 2–3 days before the event (prodrome)
  • the peri-ictal period (aura, ictus, and postictal interval)
  • the time between events (interictal interval)

Treatment of psychiatric manifestations attributable to the prodromal and peri-ictal periods should be directed toward maximizing intervention with antiepileptic drugs (AEDs). The following sections give examples for specific psychiatric symptoms.

Affective symptoms

Both manic and, more commonly, depressive symptoms can be seen related to an epileptic event itself. This phenomenon was noted first in the 1800s by Burrows and later by Falret.8 Blanchet and Frommer9 observed depressive mood changes before a seizure that took up to 3 days postictally to resolve. Williams10 found fear and, rarely, depression during the ictus, and also noted peri-ictal elation. Peri-ictal manic symptoms have been reported as well, but they are rare.11–14

Psychotic symptoms

Ictal psychosis can result from simple partial status epilepticus (with consciousness maintained) or complex partial status, with impaired consciousness. In nonconvulsive status, the symptoms of psychosis appear in the context of a delirium.15

Postictal psychosis can develop 12 to 72 hours after seizure activity, often in conjunction with a flurry of complex partial seizures. Predisposing factors are unclear but may include features such as bitemporal epileptic activity and structural lesions.15

Treatment of emergent symptoms includes neuroleptics, often given parenterally. One possible choice is intravenous haloperidol (Haldol), which is easy to administer and seems to have fewer extrapyramidal side effects than the oral preparation, although the evidence is sparse.16 The dosage is then gradually reduced, usually over the next several weeks, as tolerated by the patient. In about 15% of patients, interictal psychotic symptoms may occur after an episode of postictal psychosis. A subsequent shift to a more atypical neuroleptic can then be made.15(See Antipsychotics.)

Aggressive symptoms

Aggression also may be a manifestation of seizure activity. Aggression associated with epilepsy can be discriminated from a nonictally related event by its directionality.17 Planned and focused aggression is not of ictal origin. Aggression might ensue if postictal delirium is forcibly contained.

In epilepsy, interictal aggression may be associated with a low intelligence quotient, early onset of seizures, and a dominant-hemisphere electroencephalographic (EEG) focus.17

After determining that psychiatric manifestations are not directly related to a seizure, other possible risk factors should be evaluated before a psychotropic drug is administered. These factors include:

  • the phenomenon of "forced normalization"18
  • folic acid deficiency associated with the use of AEDs, possibly catalyzing depressive features19–22
  • side effects of AEDs themselves (such as hypomania,23 depression,24–27 and behavioral disturbances with the use of gabapentin and lamotrigine in DD)
  • AED polypharmacy, which also has been associated with psychiatric symptoms28

After a thorough assessment of these factors, if a salient psychiatric symptom persists or the instigating AED cannot be changed, a psychotropic drug should be started. The major reason that psychotropic drugs are underused in patients with epilepsy is a fear of seizure exacerbation resulting from a decrease the seizure threshold.

Adapted from: Barry JJ and Huynh N. Psychotropic drug use in patients with epilepsy and developmental disabilities. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;205–217. With permission from Elsevier (

Authored By: 
John J. Barry MD
Nga Huynh PharmD
Reviewed By: 
Steven C. Schachter MD
Tuesday, June 1, 2004