Management of Psychogenic Nonepileptic Seizures

In their review of the epidemiology of psychogenic nonepileptic seizures, Asadi-Pooya and Sperling (4) reported that psychogenic seizures are relatively common, since they are reported to be experienced by 5%–10% of outpatients in epilepsy clinics and 20%–40% of inpatients in epilepsy monitoring units. In three studies reviewed by Asadi-Pooya and Sperling, the incidence of psychogenic nonepileptic seizures was estimated to be 1.4–4.9 per 100,000 per year, and in one study the prevalence was calculated to be between 2 and 33 per 100,000.

Epilepsy has a bimodal age curve. Most cases develop among the young (due to mitochondrial or genetic disorders) and the elderly (due to strokes, tumors, or neurodegenerative conditions). Contrastingly, psychogenic nonepileptic seizures have an inverse unimodal curve, with 70% of cases developing among individuals between the second and fourth decades of life (5). There is a female-to-male ratio of 2.94, and the proportion of people with psychogenic nonepileptic seizures who also have epileptic seizures ranges from 5% to 50% (4). Individuals with a family history of epilepsy have a higher risk of developing psychogenic nonepileptic seizures. This is thought to be due to imitation via "modeling" (5). Associated factors include childhood physical or sexual abuse, traumatic brain injury (with comorbid depression, behavioral impulsivity, or posttraumatic stress disorder), medical comorbidities, and brain dysfunction (4). Additionally, anxiety disorders, dissociative disorders, and borderline personality disorder are common comorbid conditions among individuals with psychogenic nonepileptic seizures (1). Precipitants of psychogenic nonepileptic seizures include injury, death of or separation from family members or friends, job loss, rape, childbirth, surgical procedures, natural disasters, relationship difficulties, and legal problems (6).

Currently, there are substantial limitations in our study and understanding of the etiology of psychogenic nonepileptic seizures. Obstacles identified in conducting clinical trials include both intrinsic and logistical factors. Intrinsic factors are emotional lability, approach-avoidance behavior patterns, crisis presentation, rejection of support, and lack of motivation. Logistical limitations are motor vehicle operation restrictions, cognitive and physical impairments, severity of psychopathology, and unclear utility of various outcome measures (1).

A neurobiological conceptual framework has been proposed explaining psychogenic nonepileptic seizures as a dysfunction of the brain areas involved in the emotion processing responsible for sensorimotor and cognitive processes. In other words, there is a lack of appropriate integration thought to be related to vulnerability traits, such as dissociative tendencies, hyperarousal, alexithymia, avoidance, and cognitive rigidity (7). Challenges to this framework are that it is largely theoretical and that a high level of psychiatric comorbidity makes it impossible to infer that brain abnormalities observed on neuroimaging are specifically associated with psychogenic nonepileptic seizures rather than coexisting pathology (7). Despite this, multiple studies have examined changes in connectivity between the anterior cingulate cortex, insula, precentral sulcus, inferior frontal gyrus, and parietal cortex (8).

Presenting symptoms vary widely and include changes in behavior, motor activity, sensation, cognition, and automatic functions. Psychogenic nonepileptic seizures can be initially mistaken as epileptic seizures, and diagnosis is often delayed by approximately 7 years (1). Diagnosis is confirmed by using the gold standard: video EEG monitoring before, during, and after ictus (1). However, a normal EEG recording does not rule out epileptic seizures, since simple partial seizures or frontal lobe epilepsy can result in scalp-negative EEG findings (1). Neuropsychiatric histories can help in confirming the diagnosis of psychogenic nonepileptic seizures (1). Early correct diagnosis is critical, since it enables patients to receive needed treatment promptly and prevents common iatrogenic complications from inappropriate treatment with antiepileptic drugs. An estimated 75% of patients with psychogenic nonepileptic seizures receive antiepileptic drug treatment prior to accurate diagnosis (3).

Several clinical features distinguish psychogenic nonepileptic seizures from epileptic seizures. Nevertheless, many features are nonspecific and can occur in both seizure types. There is no single feature that is pathognomonic for psychogenic nonepileptic seizures, and of significance, some unusual clinical features associated with psychogenic nonepileptic seizures are also associated with frontal lobe epilepsy (5). Psychogenic nonepileptic seizures tend to occur during awake hours only, whereas epileptic seizures can occur at night. Moreover, psychogenic nonepileptic seizures lack the stereotypical nature that epileptic seizures possess (5). Specific clinical features that differentiate psychogenic nonepileptic seizures from epileptic seizures are presented in Table 1.

Serum prolactin can have diagnostic utility. The American Academy of Neurology concluded that serum prolactin measured 10–20 minutes postictal can help in differentiating generalized tonic-clonic or complex partial seizures from psychogenic nonepileptic seizures among adults and older children (9).

A 2014 Cochrane Review on psychological and behavioral treatments concluded that there is little reliable evidence to support the use of any treatment, including cognitive-behavioral therapy (CBT), for psychogenic nonepileptic seizures (10). A search conducted by using CENTRAL [Cochrane Central Register of Controlled Trials], MEDLINE, PsycINFO, and Scopus revealed three different types of treatments used in 12 different studies: CBT, psychotherapy, and hypnosis. Of the 12 studies reviewed, four were randomized and eight were nonrandomized. The majority of the studies did not use satisfactory methods, and there was a high risk of bias. Although participants in one randomized trial showed significant reduction in the number of seizures following CBT, there was little reliable evidence supporting use of any specific treatment for psychogenic nonepileptic seizures (10).

Although data are limited, it is noteworthy that CBT is the only psychotherapeutic intervention studied as a treatment for psychogenic nonepileptic seizures in randomized controlled trials and, as a result, has the highest level of efficacy evidence (1).

Goldstein et al. (11) conducted a randomized controlled trial in which both the active-treatment group and the control group received standard medical care, which consisted of seven outpatient appointments in a neuropsychiatric setting with psychoeducation, support measures, and antiepileptic drug tapering. Additionally, individuals in the active-treatment group received 12 sessions of CBT, which focused on engagement in treatment; reinforcement of independence; distraction, relaxation, and refocusing techniques at the earliest signs of an event; graded exposure to avoided situations; cognitive restructuring; and relapse prevention. Results showed that there was a significantly lower number of seizure events in the CBT group (standard medical care median, 6.75 events per month; CBT plus standard medical care median, 2 events per month [p<0.002]) (11).

LaFrance et al. (12) organized a pilot clinical trial at three academic centers where participants were randomly assigned to CBT-informed psychotherapy, medication (flexible-dose sertraline), CBT-informed psychotherapy plus medication, or treatment as usual. CBT-informed psychotherapy consisted of 12 weekly, 1-hour individual sessions targeting behaviors and cognitions in psychogenic nonepileptic seizures. Treatment as usual consisted of regular neurological follow-up appointments. The psychotherapy (CBT-informed psychotherapy) arm showed a 51.4% reduction in the number of seizures experienced (p=0.01) and significant improvement from baseline in depression, anxiety, quality of life, and global functioning (p<0.001). The combined arm (CBT-informed psychotherapy plus sertraline) showed a 59.3% reduction in the number of seizures experienced (p=0.008) and significant improvement in some measures, including global functioning (p=0.007). No improvements were observed in the other study arms.

Other psychotherapy interventions examined in randomized controlled trials include group psychoeducation, inpatient paradoxical intention (whereby a patient is encouraged to have an event), and hypnosis (13–15). These interventions have demonstrated varying degrees of improvement in terms of seizure events and psychopathology. Psychodynamic psychotherapy, in which trauma is considered the central feature of psychogenic nonepileptic seizures, has been studied by Howlett and Reuber (16), as well as others. Psychodynamic psychotherapy has demonstrated efficacy in reducing seizure frequency and severity, decreasing psychological distress, improving quality of life, and decreasing health care utilization (16–18).

There are few studies that have evaluated the utility of psychotropic medications for the treatment of psychogenic nonepileptic seizures. This can be explained by the current lack of consistent neurobiological models. To date, no single biomarker has successfully differentiated psychogenic nonepileptic seizures from epileptic seizures (19). Consequently, pharmacological treatment is targeted toward symptoms (1). An open-label noncontrolled study of flexible-dose venlafaxine showed significant decrease in seizure events, anxiety, and depression (20). Outcomes were measured over a 5-month period (20).

Despite a long-standing history, psychogenic nonepileptic seizures remain a poorly understood condition. Video EEG continues to be the gold standard for diagnosis, in addition to clinical presentation and neuropsychiatric history. Treatment includes psychotherapy with or without antidepressant use.

The burden of care for patients with psychogenic nonepileptic seizures is high. In the United States, up to $900 million is spent on emergency department utilization, diagnostic evaluations, laboratory tests, and antiepileptic drugs (6). Further research addressing barriers and utilizing larger samples and more satisfactory methodology is needed.