Psychiatric symptoms in epilepsy are the expression of at least four important processes: (i) an intrinsic epileptic process resulting from neurochemical and neurophysiological changes in the limbic circuit; (ii) an expression of the iatrogenic potential of many of the AEDs used in these patients; (iii) an expression of a reactive process to a chronic disorder that demands multiple adjustments; and (iv) a bidirectional relationship between epilepsy and some of the psychiatric disorders, such as depression, attention-deficit hyperactivity disorder (ADHD), and conditions associated with suicidality (4,5,6,7). Psychiatric symptoms can also result from the interaction between two, three or all the four processes. Accordingly, the occurrence of any psychiatric or psychosocial phenomena must be placed in the context of these possible scenarios.

We cite some examples of depressive disorders in epilepsy to illustrate these points. The expression of depressive disorder as an intrinsic process of the seizure disorder is exemplified by the higher incidence of interictal depression among patients with partial seizure disorders that involve the limbic circuitry (i.e., partial seizures of temporal lobe origin) (8,9,10,11,80,82,84). Although several studies have suggested that this incidence is higher in partial epilepsies than in generalized epilepsies (15,16,17,18,80,82,84), recent studies are questioning such beliefs (see Chapter 13).

Often, the presence of ictal and peri-ictal semiology may be an indicator of associated psychopathology. For example, patients with auras consisting of psychic symptoms have a higher rate of depression than patients with partial seizure without auras or whose auras consist of motor, sensory, or autonomic symptoms (22). By the same token, the presence of postictal symptoms of depression and/or anxiety has been associated with a significantly higher likelihood of a prior history of depression or anxiety, whereas postictal suicidal ideation is predictive of a prior history of psychiatric hospitalization (23).

With respect to the iatrogenic process responsible for psychiatric symptoms among patients with epilepsy, it is well known that all AEDs can cause psychiatric symptoms—some more than others—in these patients (24,25). Phenobarbital is known to cause behavioral disturbances, problems with attention, and depression, and to be associated with the occurrence of suicidal ideation, as well as suicidal and parasuicidal behavior (26,27,28,29,80,82,84). Primidone, tiagabine, topiramate (33), vigabatrin (32), and felbamate (34) are among the other AEDs known to frequently cause symptoms of depression. AEDs with mood-stabilizing properties, such as carbamazepine, oxcarbazepine, lamotrigine, and valproic acid, can cause similar problems (20,35), albeit with a significantly lower frequency.

There are two other iatrogenic processes that can result in psychiatric symptoms. The first process is through the discontinuation of AEDs with mood-stabilizing properties in patients with underlying psychiatric disorders that have been under control with these
AEDs. Therefore, episodes of depression, mania, or panic attacks have been reported after the discontinuation of AEDs such as carbamazepine or valproic acid (36). The second process can result from the pharmacokinetic interaction between an enzyme-inducing AED and a psychotropic drug. Specifically, AEDs such as carbamazepine, phenytoin, primidone, and phenobarbital induce the metabolism of most antidepressants and antipsychotic drugs. Hence, the addition of one of these AEDs in the presence of a psychotropic drug will result in a drop of the serum concentrations of the latter, which, in turn, may cause the recurrence of a psychiatric process that had been well controlled by the psychotropic drug at higher serum concentrations.

The following are among the psychosocial factors known to mediate the occurrence of depression: (i) the patient’s lack of acceptance and poor adjustment of his or her epilepsy (37); (ii) the stigma associated with the diagnosis of epilepsy and the well-known discrimination to which these patients are subjected (38,39,40); (iii) the lack of control in one’s life caused by the random occurrence of epileptic seizures (41,42); and (iv) the patient’s lack of social support and the need to make significant adjustments in lifestyle, such as relinquishing driving privileges or changing jobs, to ensure that seizure precautions are closely observed. These are just a few of the obstacles that the patient with epilepsy must face on a daily basis (43,44,45,46,80). The ability to cope with these obstacles is often hampered by the psychological and psychiatric problems that are not infrequent among the patient with epilepsy. For example, neuropsychological studies have shown that even patients with epilepsy with normal intelligence have a lower degree of flexibility of mental processing than normal controls (48,49,50,51,80).

In the last two decades, four studies have demonstrated a bidirectional relationship between epilepsy and psychiatric disorders such as depression and ADHD, or even between epilepsy-specific symptoms of various psychiatric disorders, such as suicidal attempts ([4,5,6], see also Chapter 1). Such bidirectional relationship implies that not only is epilepsy a risk factor for the development of these psychiatric disorders but also that the latter are risk factors for the development of epilepsy. Clearly, we do not believe that these psychiatric disorders cause epilepsy or vice versa, but rather such bidirectional relationship suggest the existence of common pathogenic mechanisms that are operant in both epilepsy and these psychiatric disorders. These data also require that we reconsider previous assumptions regarding proconvulsant properties of certain types of psychotropic drugs such as central nervous system stimulants and antidepressants, as the occurrence of seizures in patients treated with these drugs may be an expression of the increased risk that these patients have of developing epilepsy because of the underlying psychiatric disorder.

Psychopathology can be classified according to the temporal relationship between the presentation of psychiatric symptoms and the seizure occurrence into (i) ictal symptoms (the psychiatric symptoms are a clinical manifestation of the seizure), (ii) peri-ictal symptoms (symptoms precede and/or follow the seizure occurrence), and (iii) interictal symptoms (symptoms occur independently of the seizure occurrence). For example, ictal depression is the expression of a simple partial seizure (or “aura”) or of the beginning of a complex partial seizure in the form of one or more depressive symptoms. These depressive symptoms are experienced by the patient before the epileptic activity has spread to subcortical and/or contralateral structures, causing loss of consciousness. It has been estimated that 25% of patients with auras have a variety of psychiatric symptoms as their principal clinical manifestation; 15% of these involve affect or mood changes (53,54,55). In some series, ictal anxiety and fear are the most common types of ictal affect, followed by ictal depression (55). At times, mood changes represent the only expression of simple partial seizures, and
consequently they may be difficult to recognize as epileptic phenomena. These mood changes are typically brief, stereotypic, occur out of context, and are associated with other ictal phenomena.

Peri-ictal psychiatric symptoms typically precede and/or follow seizure occurrence ([23,56], see also Chapter 19). At times, prodromal symptoms of depression may extend for hours or even days before the onset of a seizure (56). Postictal psychiatric symptoms are the most frequent presentation of peri-ictal symptoms (23). They may present as isolated symptoms or in clusters mimicking psychiatric disorders, that is, postictal psychosis or depression. The postictal period comprises the time period from the moment of recovery of consciousness following a seizure to up to 5 days. Clinicians must remember that psychiatric symptomatology may often appear following a 12- to 48-hour symptom-free period after regaining consciousness. The incidence of postictal psychiatric symptoms has not been determined; however, in a recently completed study, we found the presence of postictal symptoms of depression in 43 of 100 patients with poorly controlled partial seizure disorders, with a median duration of 24 hours (23). Interestingly, postictal symptoms of depression can outlast the ictus for up to 2 weeks (50,57) and, at times, have led patients to commit suicide (58,59,60,61). Postictal psychotic symptoms were identified in 7% of patients (23).