Antiepileptic drugs

Positive psychotropic properties

Certain antiepileptic drugs (AEDs) have positive psychotropic properties, as listed on the table below. On the other hand, AEDs also can have negative psychotropic properties that produce a variety of psychiatric symptoms. Psychiatric adverse events thus can result from:

  • the discontinuation of an AED with positive psychotropic properties (in patients with a prior mood disorder that had been kept in remission with the AED)
  • the addition of an AED with negative psychotropic properties

AEDs with positive psychotropic properties*


Bipolar Disorder Social phobia Panic Psychosis(allows lower dose of antipsychotic)
Antimanic Antidepressant Prophylactic
CBZ LTG CBZ gabapentin VPA VPA
VPA VPA clonazepam

*Proven in double-blind, placebo-controlled studies.
CBZ = carbamazepine; LTG = lamotrigine; VPA = valproic acid


Psychiatric adverse events

The following table summarizes the types of psychiatric adverse events reported with the use of AEDs. It should be noted that an AED with positive psychotropic properties can still cause psychiatric adverse events.


Psychiatric adverse events related to AEDs
AED ADHD Behavior disorders Mood disorders Anxiety disorders Psychosis Forced normalization
+ + + - + -
- + + - - +
Ethosuximide - + + - + +
Felbamate - + + - - +
Gabapentin - + + - - -
Lamotrigine - + - + + -
Levetiracetam + + + - + +
Oxcarbazepine - - - - - -
+ + + + + +
Phenytoin - + - - - +
Tiagabine - + + - - -
Topiramate + + + - + +
Valproic acid - + - - + +
Zonisamide - + + - - -

AED = antiepileptic drug; ADHD = attention deficit hyperactivity disorder.

It is important to investigate the psychiatric history of the patient and his or her family, as some AEDs can cause psychiatric adverse events specifically in patients with such risks. For example, phenobarbital has been found to cause symptoms of depression more often in patients with family history of this mood disorder.

Epilepsy surgery

Patients may be considered for temporal lobectomy if their seizures are medication-refractory, if their symptoms significantly interfere with the ability to lead a productive life, and if a resectable seizure focus is identified. Most patients who undergo the procedure have a substantial decrease in their seizures and many become seizure-free. Positive outcomes include increased productivity and an improvement in social functioning and cognition.

Psychiatric complications after temporal lobectomy have been identified, however. These can be divided into several categories:

  • symptoms of mood lability, dysphoria, and anxiety noted during the first 6 to 12 weeks after surgery - these symptoms tend to remit by the sixth month
  • de novo depressive disorders
  • de novo psychotic disorders
  • exacerbation or recurrence of depressive disorders that existed prior to surgery

Postsurgical depressive disorders can be seen in about 30% to 40% of patients who undergo a temporal lobectomy. Most are transient and remit spontaneously or with antidepressant medication.

De novo depressive disorders usually occur during the first 12 months after surgery and respond to antidepressant medication. It is important to recognize them, as some can be severe enough to cause suicide attempts. A timely and effective intervention may prevent such complications. These depressive episodes can occur both in patients who become seizure-free and in those with persistent seizures after surgery.

De novo psychotic episodes are relatively rare. They are more likely in patients who undergo temporal lobe resections that included certain types of benign tumors. Antipsychotic medications must be used.

Exacerbation or recurrence of prior depressive disorders requires the reintroduction of antidepressant medication or adjustment of the dose if the patient is already taking one.

Whether epilepsy surgery should be recommended to patients with a psychotic disorder has been controversial. I believe that surgery can be offered to these patients if they clearly understand the risks and potential benefits of the surgery and the nature of the presurgical evaluation, and can cooperate with all the tests. Recent reports, in fact, have shown that the management of the psychotic disorder can be greatly facilitated when seizures are under control after epilepsy surgery.

Interictal behavioral symptoms often do not change with surgery.

Vagus nerve stimulator (VNS)

The vagus nerve stimulator, approved for use in the United States in 1997, is a pacemaker-like device that sends electrical stimuli to the brain through the vagus nerve in the neck. Besides seizure control for some people with epilepsy, this device also has been found to have positive psychotropic properties:

  • antidepressant effect
  • antianxiety effect
  • shortening of the postictal period, facilitating the recovery from a seizure and preventing or limiting the duration of postictal psychiatric symptoms.

Adapted from: Holzer JC and Bear DM. Psychiatric considerations in patients with epilepsy. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 131-148. With permission from Elsevier (

Authored By: 
Jacob C. Holzer MD
David M. Bear MD
Reviewed By: 
Andres M. Kanner MD
Thursday, April 1, 2004