Depression is the psychiatric condition most frequently identified in people with epilepsy. Nevertheless, it is very often unrecognized and untreated. It should be considered a serious problem because of its significant negative impact on the patient's quality of life and increased potential for self-injury or suicide. An important tool in understanding the variety of depressive syndromes in epilepsy is the timing of the mood symptoms in relation to the ictus:

Preictal symptoms of depression can appear hours to days before a seizure. This phenomenon has been well documented in studies utilizing rating scales for depression and associated symptoms before and after seizures. Patients typically report feelings of irritability, inability to experience any pleasure in activities, problems with concentration, and feelings of hopelessness. The intensity of these symptoms worsens over time. Symptoms usually remit after seizures, though in some patients symptoms may persist into the postictal period.

During the ictal phase, the mood may suddenly change to sadness, suicidal ideation or feeling of helplessness or hopelessness with no environmental precipitant. Symptoms of depression and fear are the two most common ictal expressions of psychiatric symptoms. Often they may be the only symptoms of the ictus, hence presenting as simple partial seizures. More often than not, however, these symptoms last less than 30 seconds and are followed by alteration of consciousness leading to a complex partial or secondarily generalized tonic-clonic seizure. Some investigators have suggested that the presence of psychiatric "auras" may be associated with a higher occurrence of interictal depressive disorders in patients with epilepsy.

Ictal crying (dacrystic seizures) is rare, despite the prevalence of unpleasant or dysphoric mood auras. Ictal laughing (gelastic seizures) is more common, yet the experience of euphoria during an ictus (a "Dostoyevskian seizure") is extremely rare. The divergence may represent an uncoupling of emotional experience from the expression of affect during the ictal phase.

During the postictal phase, symptoms of depression are common but often overlooked. In a recent study, 43% of 100 consecutive patients with intractable partial epilepsy experienced symptoms of depression after more than half of their seizures. The average duration of these symptoms was 24 hours, with a range from several minutes to up to a week. Of these 43 patients, 18 reported clusters of at least five symptoms of depression that lasted at least 24 hours and mimicked the symptoms of a major depressive episode, and 13 experienced suicidal thoughts. Most of the patients who reported symptoms of depression also reported symptoms of anxiety and disturbances in their sleep and appetite. Clearly, these symptoms have a greater impact in the life of patients than the actual seizure.

During the interictal phase, depression is the most frequent comorbid psychiatric disorder. Interictal depressive disorders result from a variety of factors including:

• chemical and electrophysiological changes in the brain resulting from the epileptic disorder itself
• a genetic predisposition to experience depression
  
• a reaction to the multiple obstacles faced by people with epilepsy
• an adverse effect of medications used to treat the seizures

The depressive disorders in people with epilepsy may be identical to those of people in the general population, but in up to 50% of people with epilepsy, interictal depressive episodes present features considered "atypical." Symptoms of irritability, poor frustration tolerance, and mood lability may be more prevalent and obvious than other symptoms typical of "classic" depression, such as inability to find pleasure in activities, problems with sleep and appetite, or feelings of helplessness and hopelessness. Their symptoms tend to last between a few hours and several days and may remit spontaneously for several days before recurring without any apparent reason. This on-off course of symptoms can persist for a very long time, to the point that patients and their families often consider these "mood changes" to be normal and "a part of the epilepsy." Thus, they fail to report them to the physician and the depressive episodes go untreated while having a significant taxing effect on the quality of life of the patients and their families.

Treatment of pre-ictal, ictal, and postictal symptoms of depression depends largely on seizure control. The efficacy of antidepressant drugs in treating postictal depressive episodes has not yet been evaluated.

A relationship between seizure control and psychotic symptoms in some patients with intractable epilepsies was described in the middle of the 20th century by a Swiss neuropsychiatrist and multiple reports have appeared in the literature since then. The observation that the EEG recordings of these patients normalized during the psychotic episode led some investigators to coin the term "forced normalization" to describe this phenomenon. Some believe that this antagonism between psychosis and epilepsy may explain the therapeutic effect of electroconvulsive therapy (ECT) for psychotic disorders.

This phenomenon, also known as "alternative psychosis," is by no means common. In one study, its prevalence was estimated to be 1% among 697 patients followed at a university epilepsy center.

Forced normalization has been reported in patients with both TLE and generalized epilepsies. A paranoid psychosis (a richness of affective symptoms without clouding of consciousness) has been its most frequent manifestation. It has been observed following the use of various AEDs, including phenytoin (Dilantin, Phenytek), carbamazepine (Tegretol, Carbatrol), ethosuximide (Zarontin), and levetiracetam (Keppra).

Recent observations have suggested that the phenomenon of forced normalization is not restricted to psychotic episodes, but may also present as episodes of major depression.

Overt aggressive behaviors occur in a minority of people with epilepsy. Certain typical features are common to most episodes of aggression in patients with TLE. These features may differ depending on when they occur:

Ictal phase

• rare, usually unintended and nondirected, related to stereotyped movements
• other signs or symptoms of seizures may be present, including EEG abnormalities

Postictal phase

• usually part of postictal confusion, irritability, depression, or pain
• tends to be brief, nondirected
• may intensify if the patient is approached or restrained Interictal phase
• tends to occur as a component of other interictal behavioral changes
• follows rather than precedes the onset of epilepsy
• patient tends to take responsibility for his or her actions, may express remorse about consequences and espouse moral or religious convictions

The last feature above is helpful in distinguishing patients with interictal aggression from those with antisocial personality disorders. Aggressive behavior among people with epilepsy may be more common in those whose early life included disruption or physical abuse, or those with histories of fire setting, animal torture, conduct disorder, or substance abuse.

Anxiety

Anxiety disorders and individual symptoms of anxiety are commonly identified in people with epilepsy. During the ictal phase, panic and fear are the most frequent psychiatric symptoms presenting as an expression of seizure activity. Often ictal fear or panic can be misdiagnosed as a panic disorder, as both types of episodes can produce similar symptoms, such as palpitations, shortness of breath, clammy hands, or pallor or flushing of the face.

To avoid an erroneous diagnosis and treatment, it is essential to distinguish between ictal panic and panic attacks. The following are the principal differences between these two types of events:

Patients are also likely to experience symptoms of anxiety during the postictal period. These symptoms include panicky feelings, constant worry, and fear of leaving the house or being left alone. In the study of postictal psychiatric symptoms mentioned above, 45 of 100 consecutive patients with poorly controlled partial epilepsies experienced symptoms of anxiety after more than half of their seizures. The average duration was 24 hours, with a range of several minutes to several days. Postictal symptoms of anxiety occurred together with symptoms of depression and disturbances of sleep and appetite.

Interictal anxiety disorders are relatively frequent and are more prevalent in people with epilepsy than in other people. They can be identical to those identified in people without epilepsy, and include panic disorders, generalized anxiety disorders, and phobias, including agoraphobia and social phobia.

Interictal anxiety disorders result from a variety of factors often acting together. These factors include:

• the neurochemical and electrophysiologic changes associated with the seizure disorder (usually affecting the temporal and frontal lobes)
• a reactive process to adverse situations
• antiepileptic drugs

The management of interictal anxiety disorders is similar to the management of idiopathic anxiety. Besides AEDs, the clinician may prescribe anxiolytic and antidepressant medications or behavioral therapy.

Dissociative experiences

Dissociative experiences, in which the patient's sense of identity and memory are disturbed, are another important class of symptoms that may develop during a partial seizure. Dissociative symptoms include depersonalization, derealization, autoscopy (looking at one's body from outside), and multiple personalities. These symptoms tend to be limited to peri-ictal periods.