AUTHOR AND EDITOR INFORMATION

Section 1 of 7  

• Authors and Editors
• Introduction
• Psychosis
• Mood Disorders
• Anxiety Disorders
• Personality Disorders
• References

INTRODUCTION

Section 2 of 7  

• Authors and Editors
• Introduction
• Psychosis
• Mood Disorders
• Anxiety Disorders
• Personality Disorders
• References

Both neurology and psychiatry deal with diseases of the same organ—the brain. Predicting interaction between neurologic and psychiatric diseases is not, therefore, unreasonable. In an editorial in the journal Neurology in 2000, Price, Adams, and Coyle explored these interactions. The clinical relationship between epilepsy and behavioral disorders remains controversial.

Some authors find a greater incidence of behavioral disorders in patients with epilepsy than in the general population. Other authors argue that this apparent overrepresentation is due to sampling errors or inadequate control groups. Mechanisms for such a relationship include the following:

• Common neuropathology
• Genetic predisposition
• Developmental disturbance
• Ictal or subictal neurophysiological effects
• Inhibition or hypometabolism surrounding the epileptic focus
• Secondary epileptogenesis
• Alteration of receptor sensitivity
• Secondary endocrinologic alterations
• Primary, independent psychiatric illness
• Consequence of medical or surgical treatment
• Consequence of psychosocial burden of epilepsy

Because of the phenomenology of epilepsy, the close association between epilepsy and psychiatry has a long history. The traditional approach to epilepsy care has been to focus on the seizures and their treatment. Concentrating only on the treatment of the seizures, which occupy only a small proportion of the patient's life, does not seem to address many of the issues that have an adverse impact on the quality of life of the patient with epilepsy. Sackellares and Berent stated that comprehensive care of the epileptic patient requires "...attention to the psychological and social consequences of epilepsy as well as to the control of seizures."

Although undoubtedly important in the care of the patient with epilepsy, advances in neurologic diagnosis and treatment tended to obscure the behavioral manifestations of epilepsy until Gibbs drew attention to the high incidence of behavioral disorders in patients with temporal lobe epilepsy. Agreement now is general that the incidence of neurobehavioral disorders is higher in patients with epilepsy than in the general population. Many, but not all, authors also accept the proposition that the link between neurobehavioral disorders and temporal lobe or complex partial epilepsy is particularly strong. Edeh and Toone asserted that the difference is between focal epilepsies, both temporal lobe and nontemporal lobe, and primary generalized epilepsy.

Vuilleumier and Jallon estimated that 20-30% of patients with epilepsy have psychiatric disturbances. Tucker reported that one study found that 70% of patients with intractable complex partial seizures had one or more diagnoses consistent with Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R)—58% had a history of depressive episodes, 32% had agoraphobia without panic or other anxiety disorder, and 13% had psychoses. Torta and Keller reported that the risk of psychosis in populations of patients with epilepsy may be 6-12 times that in the general population, with a prevalence of about 7-8% (in patients with treatment-refractory temporal lobe epilepsy, the prevalence has been reported to range from 0-16%). Differences in the rates may result from differences in populations studied, time periods investigated, and diagnostic criteria.

The psychiatric symptoms characteristic of the neurobehavioral syndrome of epilepsy (ie, Morel syndrome) tend to be distinguished in the following ways:

• Atypical for the psychiatric disorder
• Episodic
• Pleomorphic

In studying the relationship between epilepsy and psychiatric disorders, care must be taken to differentiate between the following:

• Psychiatric disorders caused by the seizures of the epilepsy - Ictal disorders, postictal disorders, and interictal disorders
• Epileptic and psychiatric disorders caused by common brain pathology
• Epileptic and psychiatric disorders that happen to coexist in the same patient but are not causally related

Schmitz et al found that multiple interacting biological and psychosocial factors determine the risk for development of either schizophreniform psychoses or major depression in patients with epilepsy and concluded that behavioral disorders in epilepsy had multiple risk factors and multifactorial etiology.

For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Epilepsy.

PSYCHOSIS

Section 3 of 7  

• Authors and Editors
• Introduction
• Psychosis
• Mood Disorders
• Anxiety Disorders
• Personality Disorders
• References

Vuilleumier and Jallon found that 2-9% of patients with epilepsy have psychotic disorders. Perez and Trimble reported that about half of epileptic patients with psychosis could be diagnosed with schizophrenia. Kanner stated that various classifications have been proposed for the psychoses associated with epilepsy. He asserted that, for the neurologist, the most useful might be that which distinguishes among psychoses closely linked to seizures (ictal or postictal psychosis), those linked to seizure remission (alternative psychosis), psychoses with a more stable and chronic course (such as interictal psychosis), and iatrogenic psychotic processes related to anti-epileptic drugs.

Ictal events: Status epilepticus (ie, complex partial status epilepticus and absence status epilepticus) can mimic psychiatric disorders, including psychosis.

Postictal events: So and colleagues distinguished between postictal psychosis, which is characterized by well-systematized delusions and hallucinations in a setting of preserved orientation and alertness, and postictal confusion, and also between self-limited postictal psychosis and the unremitting chronic interictal psychosis seen in long-standing epilepsy. Criteria proposed by Stagno for postictal psychosis include the following:

• Psychotic or other psychiatric symptoms occur after a seizure or, more frequently, a series of seizures, after a lucid interval or within 7 days of the seizure(s).
• The event may be psychosis, depression or elation, or an anxiety-related symptom.
• The event is time limited, lasting days and rarely weeks. No significant clouding of consciousness occurs. Logsdail and Toone believe that clouding of consciousness, disorientation, or delirium may be noted and, if consciousness is unimpaired, delusions and hallucinations are present; a mixture of both also may be noted. Clouding should not be attributable to other medical or psychiatric cause (eg, drug intoxication, complex partial status epilepticus, metabolic disturbance).

Interictal psychosis: Tandon and DeQuardo reviewed the series of patients with epilepsy who developed psychosis published by Slater and Beard and found that the psychosis was usually a form of schizophrenia, most commonly paranoid schizophrenia. Stagno reported that persistent interictal psychoses of epilepsy and the "schizophrenia-like psychoses of epilepsy" are distinguishable from schizophrenia in the traditional psychiatric sense by the following:

• Lack of negative symptoms of schizophrenia, particularly flattening of affect and personality deterioration
• Better premorbid personality
• Paranoid delusions
• Delusions of reference
• More benign and variable course

Risk factors for developing psychosis in epilepsy that have been found in some studies (for more details see the bibliographic entries by Trimble and Schmitz) include the following:

• Partial complex seizures, especially with temporal lobe foci: Some authors have noted a predominance of left-sided foci. Frontal lobe epilepsy is also common.
• The presence of "alien tissue" (eg, small tumors, hamartomas)
• Mesial temporal lobe gangliogliomas
• Left-handedness, especially in women

Schmitz et al studied risk factors and classified them by the following system:

• Biological factors
  • Earlier onset of epilepsy
  • More severe epilepsy
  • More frequent temporal lobe and unclassifiable epilepsies and less frequent generalized epilepsies: No significant differences in types of epilepsies between patients with epilepsy and psychosis and patients with epilepsy without psychiatric disease have been found.
• Psychosocial factors
  • Disturbed family background
  • Lack of interpersonal relationships
  • Social dependency
  • Professional failure

Trimble and Schmitz (1998) believe that the conclusions presented in the literature on risk factors are highly controversial.

Treatment

Status epilepticus and ictal abnormalities are treated in the same way as nonpsychiatric epileptic events. Postictal events are treated by improving seizure control. So et al believe that postictal psychosis remits spontaneously even without treatment but the use of effective neuroleptics may shorten the duration.

Interictal psychosis is treated with antipsychotic drugs. Medications that lower seizure threshold should be avoided. Some studies indicate that risperidone, molindone, and fluphenazine may have better profiles than older antipsychotic medications; clozapine has been reported to confer a particularly high risk of seizures.

Tarulli et al (2001) have documented cases of patients who had multiple episodes of postictal psychosis before developing interictal psychosis. They concluded that a progression from postictal to interictal psychosis may be at play and that increased awareness and prompt treatment of postictal psychosis may inhibit or prevent development of some instances of interictal psychosis.

Treatment of any of the psychoses of epilepsy should take into consideration the phenomenon termed as forced normalization, which is a concept described by Landolt in the 1950s. When the EEG in psychotic patients is normalized, often with anticonvulsant medicines, the psychiatric problem worsens. Alternative psychosis, or antagonism between seizures and behavioral abnormalities (ie, worsening of behavior with improvement in seizure control) is a similar phenomenon that has been known for a longer time. Forced normalization frequently is described in patients treated with ethosuximide; anecdotally, however, forced normalization effects have been produced by treatment with most antiepileptic agents, including the newer agents. The mechanism underlying these interesting phenomena is not yet understood. Many authors consider the idea of forced normalization to be somewhat controversial.

MOOD DISORDERS

Section 4 of 7  

• Authors and Editors
• Introduction
• Psychosis
• Mood Disorders
• Anxiety Disorders
• Personality Disorders
• References

Depression

Depression is a not an uncommon problem in patients with epilepsy. In epileptics, the reported rates of depression range from 8-48% (mean 29%, median 32%); the prevalence of depression in the general population ranges, in different epidemiologic studies, from 6-17% (Hermann and Jones, 2005). Hippocrates noted the association—"Melancholics ordinarily become epileptics and epileptics melancholics." In a study of epileptic patients admitted to a psychiatric hospital, Betts found that depression was the most common psychiatric diagnosis. The frequency of anxiety also has been addressed.

Two possibilities exist—the depression is a reaction to the chronic illness or the depression is a part of the epilepsy. Mendez et al compared patients with epilepsy to matched controls without epilepsy but with a similar degree of disability from other chronic medical diseases and found that, while 55% of the patients with epilepsy reported depression, only 30% of the matched controls reported depression. They concluded that depression is related to a specific epileptic psychosyndrome. On the other hand, Robertson concluded that, with few exceptions, the phenomenology of the depression is not to a large degree attributable to neuroepilepsy variables; however, not all studies have found this difference.

The etiology of depression in people with epilepsy is complex and includes the following:

• Genetic vulnerability
• Reaction to life events, including the epilepsy
• Effect of antiepileptic drugs
• The epilepsy, particularly temporal lobe and complex partial epilepsy

Jobe et al have presented evidence that some types of depression and some types of epilepsy may be associated with decreased noradrenergic and serotonergic transmission in the brain.

Characteristics of patients with epilepsy who also have depression include the following:

• Fewer neurotic traits
• More psychotic traits
• Higher trait and state anxiety scores
• More abnormal affect and chronic dysthymic disorder
• High hostility scores, especially for self-criticism and guilt
• Sudden onset and brief duration of symptoms

Risk factors for the development of depression in patients with epilepsy include the following:

• Temporal lobe and not frontal lobe partial complex seizures
• Vegetative auras
• Family history of psychiatric illness, particularly depression
• Laterality effects, which are controversial
  • Flor-Henry speculated that depression might be related to right (nondominant) foci, a finding confirmed by a few other investigators. Some authors have suggested that elation is associated with right-sided lesions and depression or sadness with left-sided lesions. Most studies that find a relationship between laterality and depression have found depression to be more common with left-sided foci.
  • Lopez-Rodriguez et al found that major depressive episodes were statistically more frequent in patients with left temporal lobe seizures than in patients with right temporal lobe seizures.
  • Other authors report no laterality differences in depression rates.

Categorizing depression in patients with epilepsy as depression occurring peri-ictally (preictally, ictally, or postictally) and that occurring interictally may be useful. Robertson argued that Julius Caesar may have had depression as part of his seizures. Williams studied 2000 patients with epilepsy and found that depressed mood was part of the attack in 21, the second most common emotion constituting part of the attack. Fear was the most common; others have found similar results.

Perhaps 10-20% of persons with epilepsy have a peri-ictal prodrome consisting of depressed-irritable mood, sometimes with anxiety or tension and headaches. Although Williams noted in his patients that the mood disturbance would persist for 1 hour to 3 days after the ictus, postictal affective syndromes have received little attention in the literature. Blumer has defined an interictal dysphoric disorder (IDD) in patients with epilepsy in which symptoms tend to be intermittent. On average, the patients tend to have 5 of the following symptoms (range 3-8):

• Depressed mood
• Anergia
• Pain
• Insomnia
• Fear
• Anxiety
• Paroxysmal irritability
• Euphoric moods

Kanner has noted that the symptoms of depression in patients with epilepsy are different from those in patients without epilepsy. He believes that patients with epilepsy who are felt to warrant antidepressant therapy often do not meet formal DSM criteria for a mood disorder and concludes that the problem of depression in epilepsy may be underestimated by using screening instruments designed for use in psychiatric patients. Kanner also believes that the depression in epilepsy most resembles a dysthymic disorder, and he has named this condition the dysthymiclike disorder of epilepsy.

Caplan et al believe that depression in children and adolescents tends to have a different presentation from that seen in adults, although some adolescents with depression may present with a syndrome similar to that seen in adults. They report that children with depression often do not appear sad and that the depression may be manifested by the following:

• Irritability
• Oppositionality
• Aggression
• Anger

For this reason, special instruments are used to assess depression in children. Thome-Souza and coworkers report that depression in children may be underdiagnosed and untreated for longer periods than in adults. They found that 70.5% of children and adolescents had psychiatric disorders and that the most frequent psychiatric disorder in children was attention-deficit/hyperactivity disorder and the most frequent psychiatric disorder in adolescents was depression. They found that family history was also an important determinant in mood disorders in children and adolescents.

Treatment

The treatment of mood disorders in patients with epilepsy includes re-evaluation of the anticonvulsant regimen, cautious but aggressive use of antidepressants, and psychotherapy, which also may be of use.

Improvement in seizure control should help in the treatment of ictal depression. A phenomenon analogous to alternative psychosis, worsening of behavior with better seizure control, has been reported in epilepsy-associated mood disorders. Phenobarbital is known to produce depression. According to Schmitz, vigabatrin has been linked to both psychoses and major depression, and phenytoin has been associated with toxic encephalopathies. McConnell and Duncan (1998b) cite some patients in whom phenytoin had been linked to both depression and mania. A case has been made that the GABAergic drugs may be associated with an increased incidence of psychiatric problems.

Virtually all non-monoamine oxidase-inhibiting antidepressants have been reported to lower seizure threshold. In the treatment of epilepsy-related depression, priority should be given to optimizing seizure control, since improved psychosocial functioning tends to accompany seizure remission. Antidepressants may manifest convulsant and anticonvulsant effects. Maprotiline and amoxapine have the greatest seizure risk; doxepin, trazodone, and fluvoxamine appear to have the lowest risk.

Several studies have documented that the quality of life improves significantly in epileptics who are made seizure free. If those patients are excluded, Boylan et al have found that the quality of life is related to depression but not to degree of seizure control. Both Elger et al and Harden et al have shown, in small studies, that treatment with vagal nerve stimulation improves depression in epileptics independent of effect on seizure frequency. Vagal nerve stimulation is a useful therapeutic tool in treatment-resistant depression.

Suicide

The risk of suicide in the general population averages about 1.4%. Depression is one of the psychiatric disorders that increase the risk of suicide. The risk of suicide in depressed patients is believed to be around 15%. A recent study of over 9000 manic-depressive patients identified a suicide rate of 18.9%. Pokorny has estimated that the risk of suicide in depressed patients is as high as 50 times that of the general population.

On average, the risk of suicide in patients with epilepsy is about 13% (prevalence rate ranges from 5-10 times that of the general population). Although some authors question its methodological and patient selection techniques, most authors cite Barraclough's meta-analysis, which revealed that the risk of suicide in patients with temporal lobe epilepsy is increased to as much as 25-fold that of the general population.

Mania

The best-known examples of preictal elated mood are Dostoevsky's descriptions of ictal experiences in his works The Idiot and The Possessed. In a carefully selected series of epileptic patients, Williams found that only 165 of 2000 patients had complex, including emotional, ictal experiences. Of those 165, only 3 described elation. Mania and hypomania are rare in association with epilepsy.

Manic-depressive illness is also rare; of 66 patients with epilepsy and major depression, only 2 had bipolar disease. This rarity is probably, to some degree, secondary to the antimanic effect of drugs such as carbamazepine and valproate. Mania was uncommonly associated with epilepsy even before the use of modern antiepileptic drugs.

ANXIETY DISORDERS

Section 5 of 7  

• Authors and Editors
• Introduction
• Psychosis
• Mood Disorders
• Anxiety Disorders
• Personality Disorders
• References

Anxiety in epileptic patients may occur as an ictal phenomenon; as normal interictal emotion or part of an accompanying anxiety disorder; as part of an accompanying depressive disorder; or in association with nonepileptic seizurelike events as part of an underlying primary anxiety disorder.

Anxiety is common in patients with epilepsy; of 49 epileptic patients attending a tertiary epilepsy care center, 57% had high-level anxiety. In patients with temporal lobe epilepsy, Trimble et al reported that 19% were diagnosed with anxiety and 11% with depression. Edeh and Toone found that patients with temporal lobe epilepsy scored higher for anxiety than those with focal, nontemporal lobe epilepsy. Because of the difficulty in separating the anxiety that accompanies a chronic disease from pathological anxiety, relatively few studies of anxiety in epilepsy have been done. Interestingly, Goldstein et al found that patients with epilepsy with high seizure frequency had lower anxiety scores than those with lower seizure frequency.

According to Goldstein and Harden, epileptic events can produce symptoms indistinguishable from those of primary anxiety disorder. Fear and anxiety often are associated with simple partial seizures. Torta and Keller estimated that fear occurs as an aura in as many as 15% of patients, and Goldstein and Harden concluded from several studies that fear is one of the most common ictal emotions.

Differentiating between spontaneous fear and reactive fear (ie, reaction to the knowledge that a seizure may occur) can be difficult. Panic disorder can produce paroxysmal symptoms, which can be confused with epileptic events and may go unrecognized in patients with epilepsy. Anxiety also may be related to nonepileptic attack disorder.

Torta and Keller have estimated that as many as 66% of patients with epilepsy report interictal anxiety. Goldstein and Harden proposed two major psychological mechanisms for this, as follows:

• Fear of seizure recurrence ("seizure phobia")
• Issues surrounding locus of control

They concluded that documented cases of actual "seizure phobia" are rare but that a sense of dispersed locus of control can cause profound problems in patients with epilepsy.

PERSONALITY DISORDERS

Section 6 of 7  

• Authors and Editors
• Introduction
• Psychosis
• Mood Disorders
• Anxiety Disorders
• Personality Disorders
• References

The question of personality disorders associated with epilepsy has a long history and remains controversial. Trimble has summarized the data and concluded that the personality profiles of patients with epilepsy can be explained by a complex combination of the effects of (1) dealing with a chronic illness ("being epileptic"), (2) antiepileptic drugs, and (3) temporal lobe pathology.

Waxman and Geschwind have defined a collection of behavioral abnormalities (now called the Geschwind syndrome), which they associated with temporal lobe epilepsy. Characteristics of the syndrome include viscosity, circumstantiality, hypergraphia, and less frequently, hyperreligiosity.

Benson and Hermann reported that data are insufficient to state with certainty that a consistent pattern of behavioral changes occurs in patients with temporal lobe epilepsy. Complex partial epilepsy should not be diagnosed on the basis of the presence of Geschwind syndrome alone, without any paroxysmal episode that can be proved to be epileptic.

REFERENCES

Section 7 of 7

• Authors and Editors
• Introduction
• Psychosis
• Mood Disorders
• Anxiety Disorders
• Personality Disorders
• References

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Article Last Updated: Aug 29, 2006