Psychiatric comorbidities in epilepsy.

In refractory epilepsies, the rate of mental syndromes is significantly higher than in the general population, occurring in one in three patients [1]. Here, affective and anxiety disorders are in the foreground. Looked at another way, patients with psychiatric disorders have a higher risk of developing epilepsy. These observations suggest that common pathogenetic mechanisms are present.

In everyday life, the occurrence of psychiatric comorbidities in rapidly and successfully treated epilepsies seems to be about as frequent as in the normal population. The situation is different in refractory epilepsies, where the rate of mental syndromes is significantly higher than in the general population, occurring in one in three patients [1]. Here, affective and anxiety disorders are in the foreground. Looked at another way, patients with psychiatric disorders have a higher risk of developing epilepsy. These observations suggest that common pathogenetic mechanisms are present.

Since the presence of a mental disorder can significantly influence the course of treatment of epilepsy, a psychiatric history should be standard in these patients [2]. When assessing the mental disorder, attention should be paid to the time course between the onset of the mental disorder and the epileptic event. Mental disorders as an expression of an epileptic seizure are distinguished from interictal mental disorders. To take this into account, the International League Against Epilepsy (ILAE) designed its own classification of mental disorders. Furthermore, mental disorders that may occur independently of epilepsy should also be considered. Due to the broad field, only some of the aspects relevant in clinical practice will be highlighted in the following.

Psychoses in epilepsy

Psychotic disorders in epilepsy are divided into ictal, postictal, and interictal psychoses with respect to their occurrence to epileptic seizures, and these occur mainly in patients with temporal lobe epilepsy [3].

Postictal psychosis is characterized by a sudden onset after an epileptic seizure and usually lasts between 16 hours and 18 days, with a mean of 3-4 days. Characteristic here is a lucid interval of up to 24 hours between the seizure and the onset of psychosis, during which the patient’s consciousness is not clouded. In severe cases, symptomatic treatment with neuroleptics or benzodiazepines may be indicated, otherwise the symptoms remit spontaneously. It is debated whether postictal psychosis is a time-limited, seizure-dependent autoantibody-mediated encephalopathy. During the course, approximately 14-20% of these patients develop interictal psychosis [4].

Interictal psychosis usually occurs years to decades after the onset of chronic refractory epilepsy. They differ from primary schizophrenias in clinical impression in that there is rarely a positive family history, negative symptoms are rarely severe, and despite chronicity, there is often a benign course. In addition, interictal psychosis is indicated by the fact that the onset of the illness is usually beyond the second or third decade of life and that executive and communicative functions are preserved despite chronic delusional symptoms. In clinical practice, interictal psychoses are treated like primary schizophreniform disorders.

Anticonvulsant-induced psychosis can occur as part of forced normalization with particularly effective anticonvulsants, although the mechanism here is still unclear [5]. Forced normalization is a rapid improvement in EEG abnormalities that begins after starting a new antiepileptic drug but is associated with the onset of psychotic symptoms. In the treatment of psychotic syndromes with atypical neuroleptics such as quetiapine, olanzapine, and risperidone, the risk of seizures is relatively low at 0.3-0.9%, which is why these are preferable to clozapine, which has a seizure risk of approximately 3.5%.

Affective disorders in epilepsy

Prodromal, postictal, and interictal dysphoria are characterized by the same clinical symptoms, such as thin-skinnedness, irritability, and aggressiveness. In the course of the disease, the initially still seizure-related pre- or postictal dysphoria may decouple from the recognizable seizure event and may also occur interictally. Clinically, the focus is then on short phases (hours to days) with the above symptoms, which can be diagnosed by the Interictal Dysphoric Disorder Inventory (IDDI) [6].

Patients with epilepsy are 43% more likely to get unipolar depression. Whereas, according to recent studies, 21.9% of patients in epilepsy clinics have major depression and women have a significantly higher prevalence (26.4% vs. 16.7%) [7]. Instruments such as the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) [8], which is also available in a German version [9], are suitable for specific screening. Treatment is recommended according to the Guidelines for the Treatment of Depression [10]. Modern antidepressants such as SSRIs and SNRIs can be used for drug treatment. Fears that these drugs may increase seizure frequency are unfounded based on clinical experience and available data [8].

Anxiety Syndromes

Clinically, it is often difficult to separate anxiety symptoms from depressive symptoms because in practice they go hand in hand. Patients with epilepsy are more likely to suffer from anxiety disorders than the normal healthy population. However, a specific screening tool for this subgroup does not exist [11]. Recent depression, medication side effects, low education, chronic reduced health status, female gender, and unemployment may be risk factors for developing an anxiety disorder [12].

Clinically, a distinction can be made between ictal as well as periiictal anxiety phenomena, psychoreactive anxiety before seizures, specific phobias, anxiety as a consequence of anticonvulsant medication, and anxiety as a partial aspect of other mental disorders.

Ictal anxiety syndromes are of particular importance because they are very common. Of note are the anxiety auras in mesial temporal lobe epilepsy, in which there is most likely amygdala involvement in the seizure event. In everyday life, it can therefore be difficult to differentiate between panic disorder and ictal anxiety in terms of a simple-focal seizure [13]. Indications of a panic disorder can be specific trigger conditions in stressful situations or the directionality of the fear towards an event or object (e.g. heart attack etc.).

Periiictal anxiety syndromes as pre- and postictal phenomena are integral components of dysphoric disorder in epilepsy and common in refractory focal epilepsies with a prevalence of approximately 45%. The psychoreactive fear of recurrent seizures and their consequences, which occurs in the context of epilepsy, can develop a momentum of its own in the course of the disease, which is very stressful and represents a significant restriction of the quality of life.

Agoraphobias and social phobias are found as specific phobias in the context of epilepsy. Patients develop a great fear of suffering seizures in public, of becoming unconscious, or of being exposed to the gaze of onlookers. Although this is a psychoreactively appropriate fear, cognitive behavioral therapy should be considered if avoidance behaviors resulting from fear are increasingly limiting the individual’s daily life.
However, anxiety symptoms can also be iatrogenically triggered by anticonvulsant drugs, which is why an analysis of the temporal relationship between the onset of anxiety symptoms and a new onset or dose increase of the antiepileptic drug can be groundbreaking in the diagnosis [14].

Dissociative seizures

Dissociative seizures are psychologically induced non-epileptic seizures characterized by sudden changes in behavior and consciousness, but not accompanied by changes in EEG activity as would be expected in an epileptic seizure. These occur in approximately 10% of patients with pre-existing epilepsy [15]. Patients should be trained to distinguish between the two types of seizures to make recording in the seizure calendar for epileptic seizures more reliable [16]. This often proves difficult in everyday life for those affected. The therapy of comorbid epileptic and dissociative seizures requires a very close cooperation between epileptological and psychotherapeutic treatment.

Summary

In general, achieving seizure freedom is the most important factor in the mental health of patients with epilepsy. Since mental illnesses such as depression or anxiety disorders are often underdiagnosed in this patient group and the risk of suicide is also three times higher than in the healthy normal population, the assessment of psychopathological findings and, if necessary, the initiation of appropriate treatment should be part of routine clinical practice.

Take-Home Messages

Patients with epilepsy should be routinely screened for the presence of comorbid psychiatric disorders.
Depression and anxiety disorders can sometimes affect the quality of life of epilepsy patients more than the seizures themselves.
Most modern antidepressants can be used without concern for thymoleptic/anxiolytic therapy in patients with epilepsy in view of any proconvulsive risks.
Cognitive-behavioral and other recognized psychotherapeutic procedures are indicated especially for anxiety disorders, but also for depression and coping difficulties.

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