Phenytoin chemical structure
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Phenytoin sodium (marketed as Dilantin® in the USA and as Epanutin® in the UK, by Parke-Davis, now part of Pfizer) is a commonly used antiepileptic. It was approved by the Food and Drug Administration in 1953 for use in seizures. Phenytoin acts to damp the unwanted, runaway brain activity seen in seizure by reducing electrical conductance among brain cells. more...

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Phenytoin (diphenylhydantoin) was first synthesized by a German physician named Heinrich Biltz in 1908. Biltz sold his discovery to Parke-Davis, which did not find an immediate use for it. In 1938, outside scientists including H. Houston Merritt and Tracy Putnam discovered phenytoin's usefulness for controlling seizures, without the sedation effects associated with phenobarbital. There are some indications that phenytoin has other effects, including anxiety control and mood stabilization, although it has never been approved for those purposes by the FDA.

Jack Dreyfus, founder of the Dreyfus Fund, became a major proponent of phenytoin as a means to control nervousness and depression when he received a prescription for Dilantin in 1966. Dreyfus' book about his experience with phenytoin, A Remarkable Medicine Has Been Overlooked, sits on the shelves of many physicians courtesy of the work of his foundation. Despite more than $70 million in personal financing, his push to see phenytoin evaluated for alternative uses has had little lasting effect on the medical community. This was partially due to Parke-Davis's reluctance to invest in a drug nearing the end of its patent life, and partially due to mixed results from various studies.

Dilantin made an appearance in the 1962 novel One Flew Over the Cuckoo's Nest by Ken Kesey, both as an anticonvulsant and as a mechanism to control inmate behavior.


At therapeutic doses, phenytoin produces horizontal gaze nystagmus, which is harmless but occasionally tested for by law enforcement as a marker for drunkenness (which can also produce nystagmus). At toxic doses, patients experience sedation, cerebellar ataxia, and ophthalmoparesis, as well as paradoxical seizures. Idiosyncratic side effects of phenytoin, as with other anticonvulsants, include rash and severe allergic reactions.

There is some evidence that phenytoin is teratogenic, causing what Smith and Jones in their Recognizable Patterns of Human Malformation called the fetal hydantoin syndrome. There is some evidence against this. One blinded trial asked physicians to separate photographs of children into two piles based on whether they showed the so-called characteristic features of this syndrome; it found that physicians were no better at diagnosing the syndrome than would be expected by random chance, calling the very existence of the syndrome into question. Data now being collected by the Epilepsy and Antiepileptic Drug Pregnancy Registry may one day answer this question definitively.

Phenytoin may accumulate in the cerebral cortex over long periods of time, as well as causing atrophy of the cerebellum when administered at chronically high levels. Despite this, the drug has a long history of safe use, making it one of the more popular anti-convulsants prescribed by doctors, and a common "first line of defense" in seizure cases. Phenytoin may also cause gingival hyperplasia.


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Nonepileptic Seizures: Reframing the Diagnosis
From Perspectives in Psychiatric Care, 4/1/05 by Thompson, Noreen C

PROBLEM: Protocols for disclosing the diagnosis of psychological pseudoseizures have been developed. However, outcomes have not been carefully studied.

METHOD: Using a retrospective design, the investigators evaluated the outcomes by interviewing patients 2 years after diagnosis who received the diagnosis using a specific protocol.

FINDINGS: There was a reduction in symptoms demonstrated by reports of lessened intensity of events or actual reduction in the number of events in 86% of those interviewed.

CONCLUSION: This protocol proved helpful in the acceptance of the diagnosis and improved adherence to the treatment recommendations after disclosure of the diagnosis.

Search terms: Nonepileptic seizures, psychogenic, stigma, video-monitored EEG, psychotherapy, sexual abuse


It is estimated that 17-30% of patients referred to comprehensive epilepsy centers have nonepileptic seizures (Gummit, 1993; Wilner, 2000). An epileptic seizure is defined as a sudden, involuntary, time-limited alteration in behavior, motor activity, autonomie function, consciousness, or sensation, accompanied by an abnormal electrographic pattern (EEG). A psychogenic or nonepileptic seizure is a paroxysmal "nonepileptic event" that derives its name from its clinical similarity to epileptic seizures, in the absence of concurrent electrographic ictal pattern. Because the management of psychogenic seizures is completely different from that of epileptic seizures, establishing the correct diagnosis is of extreme importance (King, Gallagher, & Murvin, 1982; LaFrance & Devinsky, 2004).

Nonepileptic seizures (NES) may include altered movement, emotion, and sensation, or disturbances in consciousness but in the absence of any changes on the electroencephalogram (EEG) that would explain the symptoms. Patients who take anti-epileptic (AE) medications but still have poor control of their seizures are often referred to epilepsy centers for prolonged inpatient EEG video monitoring. In order for the neurologist to view the seizure along with concurrent brain wave activity, AE medications are withdrawn and the patient is video-taped when the seizure occurs at our Midwest Medical Center.

With the advent of video-monitored EEG sessions, the diagnosis of psychogenic or NES can be made at the time of seizure in a very concrete way, as the EEG coincides with the seizure event (King, Gallagher, & Murvin, 1982).

Management of these patients is challenging for several reasons. Most importantly, the patient generally reacts negatively upon hearing that the seizures are psychogenic or nonepileptic. The most usual reaction is either "You think I am crazy" or "You think I am faking." The patient who suffers with nonepileptic or psychogenic seizures is generally told to seek help from a psychiatrist or other psychotherapist and to stop seeing the neurologist because their EEG is normal. Due to the perceived stigma of having a psychiatric diagnosis, the patient often seeks a second opinion hoping to hear that they do in fact have a neurological problem, which the patient perceives as more legitimate. The patient may continue to insist that AE medications are needed and frequently visit the emergency room, sometimes being admitted to an ICU in what is misdiagnosed as status epilepticus. This can be life threatening, as the patient may receive enough phenobarbital to cause respiratory distress.

This article focuses on the management of the actual disclosure of the diagnosis to the patient. We share the positive patient outcomes we have noted clinically with the incorporation of a protocol introduced by Shen, Bowman, and Markand in their classic 1990 article entitled, "Presenting the Diagnosis of Pseudoseizures," based on an approach to disclosure of this diagnosis (Shen, Bowman, & Markand, 1990; Wilner, 2000). We will describe our modified protocol. The positive outcomes include an increase in the number of NES patients willing to seek psychotherapy treatment postdisclosure of the diagnosis. We will report the frequency of at least an initial appointment with a therapist postdiagnosis in one Midwest patient population. We also describe, in detail, patterns found in the type of actual body reactions or movements in 50 patients who were video-monitored.

Literature Review

It is well known that this patient population overutilizes costly emergency department and inpatient medical services, including ICU admissions for "status epilepticus." Elizabeth Bowman provides a comprehensive review of the studies, which look at the parameters associated with NES outcomes. Dr. Bowman notes that the high prevalence of depression in the pseudo-seizure population is far more than a chance association and suggests that clinicians should always evaluate these patients for depression (Bowman, 2001). The majority of patients with NES are affected by seizures that are psychogenic in origin. These individuals are unaware of any underlying motivation and do not consciously cause the seizure (Lancman, Lambrakis, & Steinhardt, 2001). As a group, patients with NES have been identified to have a variety of comorbid psychiatric conditions that include, but are not limited to, conversion disorder, somatization disorder, dissociative disorder, personality disorder, anxiety disorder, and mood disorder (Bowman, 2001). There is also an increased prevalence of sexual, physical, and emotional abuse reported (Lesser, 1996). Typically, when patients are presented with this diagnosis there may be a defensive response as a result of the patient and/or family's perception that the patient is either "crazy" or making these events happen. Typically, the patient does not make or keep appointments with mental health professionals.

The term nonepileptic is preferable because it includes both organic and psychological events and carries no pejorative connotation. A small minority of these paroxysmal events represent physiologic problems, such as hypoglycemia, syncope, tics, transient global amnesia, or transient ischemic attacks. Each patient must be evaluated to determine if there is a physiologic cause. Approximately 75% of patients with NES are women (Krumholz & Niedermeyer, 1983; Lempert & Schmidt, 1990). Epileptic seizures rarely last longer than 2 min, whereas NESs as a rule last much longer than 2 min (Lancman, Lambrakis, & Steinhardt, 2001).

It is essential to favorable outcomes that the patient believe the diagnosis is truly nonepileptic or psychogenic. Our emphasis in speaking with the patient and family is to help them reframe or think about the diagnosis in a more positive way, so they will be willing to receive the psychological support they truly need. Otherwise, the pursuit of more and more neurology opinions "to prove there is nothing psychologically wrong" could lead to unnecessary use of AE medications. If the seizure continues on for a long time, then the patient is treated aggressively with phenobarbital and dilantin. The patient's breathing may be compromised as more and more drugs are ordered to stop the seizure activity. The psychogenic seizures can last up to an hour or more in some cases and may be wrongly diagnosed as status epilepticus when a patient presents to an emergency room.

Patients go from doctor to doctor looking for a physiologic basis for their spells. Physicians become frustrated and sometimes do not see the difference between a malingering patient and a patient with psychogenic seizures; this further complicates the patient's sense that everyone thinks badly of him or her. Malingering is consciously presenting symptoms of an illness usually for secondary gain purposes. Malingering is rarely seen in clinical practice.

In one study, a family history of epilepsy was found in 37.6% of patients with psychogenic seizures (Lancman, Brotherton, & Asconape, 1993).

There is an increased prevalence of a history of sexual and physical abuse in this population. It is clear that this is an extremely vulnerable group of patients who suffer from low self-esteem (Binder, Salinsky, & Smith, 1994; Bowman, 1999; Bowman & Markand, 1996; Drake, Pakaines, & Phillips, 1992).

The Protocol

Shen, Bowman, and Markand outlined a protocol for the presentation of the diagnosis of NES, by conveying the nonepileptic nature of the spells without alienating the patient. To achieve this, one must reframe the way the patient thinks about his or her diagnosis at every interaction. We modified the Shen approach in several ways. For example, we do not watch the videotape with the patients, unless they request it. We also do not specifically ask about past sexual abuse. Instead, we ask about any past traumas. In interviewing the patient, we find it helpful to ask about a history of traumatic or stressful life events. Most of the patients with this diagnosis volunteered information about sexual abuse or incest when asked about generic traumatic events. Review of the literature indicates that sexual abuse and incest are frequently reported by patients with this diagnosis (Goodwill, Simms, & Bergman, 1979; Gross, 1979; Gummit & Gates, 1986; LaFrance & Devinsky, 2004; Lesser, 1996).

Steps of the Protocol

1. Good News: The epileptologist explains that the spells recorded on the video-monitor were nonepileptic. The terms "psychogenic" and or "pseudoseizure" are never used unless the patient asks about those terms. We emphasize that the good news is that the spells are not the result of brain damage or excessive firing of brain waves. We emphasize that although we don't know the exact cause of the seizure or spells, they are more likely the result of excess psychological energy. We state that it is good that the patient will be able to stop taking the medications that may have produced undesirable side effects. We believe that the compassionate explanation of the diagnosis by a trusted neurologist is the first step in the treatment of these seizures.

2. Bad News: Then it is explained that we cannot tell the patient exactly what is causing the symptoms. However, knowing they are not epileptic is a start in that we know they won't improve by taking AE medications. We emphasize that we want to continue to work with the patient. The patient usually continues to see the epileptologist while being weaned off the AE medications, most importantly, to maintain the patient-physician relationship to avoid any feelings of abandonment before the patient begins to form a relationship with a psychotherapist.

3. Suggest psychotherapy: Our script begins, "In most patients with this type of seizure, we eventually discover that the cause is related to either excessive emotional energy or upsetting emotions. Often the patient isn't aware of the cause of these feelings. Our patients report they often find help by seeing a psychotherapist, and we would like to help you identify who to visit for this type of support."

4. "We do not think you are crazy or faking these spells." This is a very essential part of the discussion. We always address this issue whether the patient mentions this or not. We give the patient two copies of our educational handbook, Nonepileptic Seizures: A Guide for Patients and Families-Your Passport to Wellness. The handbook explains the diagnosis. We encourage the patient to share the book with their therapist (Table 1). Written material about the diagnosis reinforces that the team sees their seizures as a legitimate illness. It helps the patient have hope in seeking the recommended psychiatric treatment.

5. Power of suggestion: "These spells may resolve over time. Many of our patients report that after accepting the diagnosis they notice less frequent or intense spells. You may also find that you have more control over the spells, by saying to yourself, 'I am not going to have any spells today' or by concentrating on breathing easily in and out, if you feel one coming on."

6. Emphasize the importance of having hope that these spells can abate, if they seek psychotherapy support and work on a plan for stress management. It is important to understand the patient's journey through the healthcare system to truly understand their anger, frustration, and defensiveness upon hearing the diagnosis of psychogenic seizures. Active listening to their individual medical journey is also a step in establishing trust, which is so crucial in the actual acceptance of the NES diagnosis. Continue to emphasize it is good news that the seizures are not caused by any brain abnormalities.


A psychoeducational intervention is employed by the Comprehensive Epilepsy Center team when it is suspected that the seizure type is considered nonepileptic (psychogenic).

We examined whether this specific approach to orienting patients to the diagnosis and need for mental health assessment and counseling will improve compliance with a discharge plan, which includes psychotherapy. Desired outcome was defined as psychotherapy sessions after disclosure of the NES diagnosis. Desired outcome also included decreased or less intense seizures at a year or more postdischarge. It is not our purpose to evaluate types of therapy. We only sought to record how many patients actually followed the treatment advice.

We determined whether this educational approach would increase compliance with recommendations for future psychotherapy sessions. Diagnosis was established by the attending epileptologist based on review of the video-taped behaviors and lack of EEG changes during the seizures. Exclusionary criteria were as follows: coexisting neurological disorder, suspected factitious disorder, and/or epileptic seizures. Inclusionary criteria were as follows: NES diagnosis and ability to participate in mental health counseling.

We compiled our data through our normal followup telephone or in person contact with our patient population. The data were collected through conversations with the patient. A problem in our method is that perhaps a patient's self-report was not always completely accurate. However, we thought that the data support the continued use of the Shen protocol approach and the added value of having an advance practice nurse who is able to spend time truly working on reframing the diagnosis.

Fifty patients were followed who met the criteria. The patient was informed of the diagnosis by the epileptologist. This approach consists of telling the patient that there are two broad categories of seizures: one being epileptic and the other nonepileptic. The physician then explains that when the seizure occurs without abnormal EEG changes, those seizures are considered nonepileptic.

The Psychiatric Nurse's Role

During the patient's hospitalization, a psychiatric consultation liaison nurse (PCLN; a nurse with a graduate degree in psychiatric mental health nursing) met with the patient and their family members to establish rapport, and talked with the patient and any family member about the difficulties they have encountered while living with seizures. The PCLN also determined through interview if the patient was suffering with clinical depression or anxiety, based on DSM IV-R criteria. If that was the case, a psychiatric consultation was offered to assist the patient with suggestions for appropriate psychotropic medications. The PCLN met again with the patient at the time or shortly after the patient received the news of the NES diagnosis. The PCLN imparts the optimistic message that this type of seizure may lessen or stop with appropriate treatment and, most importantly, emphasizes the unconscious, nondeliberate intent of these seizures with the patient and the family.

In our clinical experience, it usually takes multiple attempts to convince the patient or family that we do not think that they are faking or "crazy." The patient and close family members are given educational information about NES in the form of a booklet entitled: Nonepileptic Seizures: A Guide for Patients and Families (Benbadis & Stagno, 1994). The PCLN reinforces the positive nature of the diagnosis by stating that with proper treatment, 70% of patients report that the seizures eventually disappear. Emphasis is placed on the "good news" of this diagnosis, including the potential of being able to drive again, come off the medications they are currently taking, as well as learning additional ways of coping with normal life stressors with the help of a therapist. A discussion of the patient's and family members' reactions to the diagnosis and the proposed need for psychiatric services are included.

Often, it takes much effort to remove the patient's sense of being stigmatized if he or she seeks psychiatric care. Frequent responses include: "I never wanted to believe this was only mental," "I feel so ashamed," or "This is such a stigma." In doing this work, it became clear to us that the patients and families were able to accept the diagnosis when time was spent in establishing rapport and their specific preconceived ideas about psychiatry or psychotherapy were addressed. This is often a time-consuming process; therefore, utilizing a nurse has proven a therapeutic and cost effective strategy. Another benefit is that the PCLN provides the direction of a mental health professional grounded in psychotherapeutic skills.

Patients tended to worry about this being "all in my head" or would ask, "Does this mean I am crazy?" After spending years seeing doctors, especially neurologists, the patient tends to reject the idea of seeing a psychiatrist. Some patients' families had implied for years that the patients were substandard in many ways, and this work is very fulfilling in that with enough time and compassion, we could improve the patient's sense of strength. The script in these cases would be: "Do you see how strong you really have been? As a child when an adult hurts you it isn't possible for you to understand or protect yourself, and this was nature's way to keep you sane and not make you crazy." Patients would sometimes cry and say that no one ever told them they were strong or had courage. Once they trusted that we saw them in such a positive light, patients were definitely more willing to see a therapist.

Other patients responded with, "I don't have any mental problems." The challenge was to individualize the efforts and try to find out the truth of the patient's and or family members' biases against psychiatry. It is very important to take time and not to become defensive while exploring this with them. Our efforts have enlisted acceptance of a mental health referral in 9 out of 10 patients diagnosed or 90%. If the patient consents, every effort is made to establish an initial appointment with a psychotherapist prior to discharge.

Review of Videotapes

In reviewing the videotapes of the 50 patients in this study, the following patterns emerged: In six patients, there was coughing before and/or during the event. In six patients, there was arching of the back. In six patients, there was head jerking often like an indication of "no." In six patients, there was nausea, gagging, or swallowing motions. In five patients, there was crying noted. In five patients, there was flexing or jerking motion of the hips. In four patients, there were signs of pain, e.g. moaning. Two patients took on a fetal like position (Table 2). These patients appear to be experiencing something very upsetting. These patterns may display the symbolic reliving of the original trauma with the body memory.

It is easy to see similarities between their actions and reactions to specific types of trauma. For instance, moaning and groaning could be a reaction to pain. When the patient is gagging, swallowing, and complaining of nausea this could be a reaction to something being forced into one's mouth. The arching and flexing of the hips often looks like unpleasant or unwanted sexual intercourse. A study comparing the actual body reactions with the lived history of abuse would be of interest to determine the relevance of this clinical observation.

Patient Outcomes

Contact was made with 48 of the 50 patients in the study. Of those 48 patients, 100% attended anywhere from one to eight psychotherapy sessions. Twentyfour patients (50%) reported that their seizures were gone 2 years postdiagnosis and of the remaining 24 patients only five reported no change. One patient was diagnosed with a movement disorder and the other four were no longer attending any psychotherapy sessions. The remaining 19 patients noted improvement described as less-intense events and/or a decrease in occurrence (see Table 3).


These results are encouraging. Patients diagnosed with NES can be compliant with a discharge plan that includes psychotherapy administered by caring and empathie therapists who are hopeful that the client can get well. Many patients experienced improvement in the number and/or intensity of the NES events. The time spent in helping our patients accept the diagnosis without shame or stigma has surely paid acceptable dividends. Using an advanced practice psychiatric nurse to establish rapport with the patient and/or family during the hospitalization is a cost-effective way to accomplish the goal of decreasing the felt experience of shame and stigma so often experienced by the patient. The nurse can screen the patient for other psychiatric diagnoses as well. Patients and families appreciate the written educational handbook, since the very offering of the book takes some of the perceived stigma away from the diagnosis.

Acknowledgments. We would like to express our gratitude to Dr. Carol Smith, Professor of Nursing at the University of Kansas School of Nursing, and Dr. Arlene D. Houldin, Associate Professor at the University of Pennsylvania School of Nursing, for their encouragement and editorial advice during the writing of this publication. We also acknowledge the support of our colleagues Mary Ann Kavalir, RN, MN, ARNP, and Mary Komosa, RN, BSN, at the University of Kansas Medical Center's Comprehensive Epilepsy Center. Finally, special thanks to Lauren E. Thompson and Lisa Voorhies for their editorial advice.


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Noreen C. Thompson, RN, MSN, CS, ARNP, Ivan Osorio, MD, and Edward E. Hunter, PhD

Noreen C. Thompson, RN, MSN, CS, ARNP, is Psychiatric Liaison Clinical Nurse Specialist, University of Kansas Medical Center, Department of Nursing, 3901 Rainbow Blvd., Kansas City, Kansas 66160-7220. Ivan Osorio, MD, is Professor, University of Kansas Medical Center, Department of Neurology, 3901 Rainbow Blvd., Kansas City, Kansas 66160. Edward E. Hunter, PhD, is Clinical Associate Professor, University of Kansas Medical Center, Department of Psychiatry and Behavioral Sciences, 3901 Rainbow Blvd., Kansas City, Kansas 66160.

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