Community Based Anti-Epileptic Treatment in theDevelopmentally Disabled

Ross FineSmith, MDClinical Instructor of NeurologyNYU School of Medicine Medical

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Introduction

This chapter reviews the unique factors associated with the

management of epilepsy and antiepileptics drugs (AED) in the

community based population of individuals with developmental

disabilities (DD).

Many of the same principles that are established for AED therapy

in the non-handicapped population can be applied to the individual

with a DD. These principles can be used as guidelines when making

decisions about initiating drug therapy or determining the most

appropriate AED 1. These guidelines are listed in Table 1-1. There are

additional specific challenges to the physician in the community

treating patients with epilepsy and a moderate to profound DD. These

factors include; a higher incidence of difficult to control seizure

disorders, individual cognitive disability may limit feasibility of

neurodiagnostic testing, adverse effects are difficult to assess in those

with limited communicative ability and patients with a DD are more

likely to experience adverse effects from

AED’s 2.

The Relocation of Persons with Disabilities

In the past, most patients with severe disabilities and epilepsy were

treated by pediatricians or pediatric neurologists and were often

admitted to long term care

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facilities in late childhood or as young adults where staff physicians

provided

their medical and neurological care. The current trend of

deinstitutionalization of individuals with moderate to profound DD’s

has “relocated” this group to a variety of community settings

including; group homes, sponsored living, supported living

arrangements and supervised apartment living. Their medical and

neurological care is now the responsibility of physicians located in

these regions. Unlike the staff physicians in the developmental

centers, most physicians in the community have limited experience or

exposure to persons with significant DD’s. This is not a result of

discrimination, but one simply of demographics. These patients were

institutionalized and typically did not receive treatment from outside

physicians. The relocating process has resulted in a marked increase

in medical consumers with DD’s requiring medical care in our

communities.

In the state of New Jersey there were 5,841 people in

developmental centers in 1986 and as of March 1999, there were

3,623. These 2000 persons have been relocated and are now living in

many communities throughout New Jersey. The number of individuals

residing in group homes has tripled in the last 8 years and, in addition,

there are 2,900 persons on the urgent waiting list and 1,000 on a non-

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urgent waiting list 3,4. This is a national trend and is not specific to one

state5.

The relocation has been especially challenging to those

physicians treating patients with epilepsy. There is a 30-50%

incidence of epilepsy in individuals with DD’s 6 and as many as 45% of

those have medically refractory epilepsy (MRE)7-9. Patients with MRE

require significantly more of the physicians practice time, than other

patients in the community with epilepsy. This group of patients needs

more aggressive management and treatment and often requires the

use of recently approved AED’s, novel therapies such as the vagal

nerve stimulator and the ketogenic diet, and when appropriate, a

referral for evaluation for epilepsy surgery.

The remainder of this paper is designed to familiarize and aid in

the development of a community-based program to more effectively

treat patients with epilepsy and moderate to profound DD’s.

Legal Guardians and Family Members

Approximately 50% of individuals that are approved and eligible for

services from the Division of Developmental Disabilities (DDD) are

residing with parents or family members3. Many of these persons are

on the waiting lists for group home placement. These individuals will

frequently be seen by the same family physician that has cared for

them most of their lives. Referral to a neurologist may occur if there is

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an initial seizure or a change in seizure status in those with pre-

existing epilepsy.

Family members have a personal interest in the care of a relative

and this may reflect in the accuracy of the interval history,

management of medication and vigilance in reporting undesirable side

effects. However, aging parents may have difficulty remembering to

give medications, accurately count seizures and recognize side effects.

Parents may have difficulty physically transporting their child to the

office or hospital. This especially problematic if the child has a physical

handicapping condition, such as cerebral palsy.

Most individuals with a moderate to profound DD with cognitive

impairment are evaluated and assessed not to be competent to make

discussions for their own well-being. A legal gaurdian must therefore

be appointed. Parents and other family members may live nearby and

be involved with the DD person’s care and elect not to be the legal

guardian. In addition, many individuals have no close family members

involved and legal guardianship is assigned to a legal representative

within the DDD. It is good practice to routinely obtain the name and

address of the legal guardian and contact them by phone to establish a

relationship. It is necessary to call if there are any questions regarding

the need for written consent for a given procedure. Changing

medications, laboratory blood work, non-invasive radiological and

electrophysiological studies usually do not require consent. However,

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conscious sedation and general anesthesia are occasionally required to

perform a test or procedure, and since this involves additional medical

risk, written consent should be obtained in advance. The risks and

benefits of any invasive procedure should be discussed with the legal

guardian. There are few individuals with moderate DD’s who are their

own guardian. Whether the person has a legal guardian or not, all

medical discussions should be attempted to be explained to the

patient personally. There are also laws governing the enrollment of

persons with DD’s into research protocols. The research protocol must

be approved by a regional Institutional Review Board and the states

DDD research committee. This was established to ensure that these

patients are not unnecessarily enrolled in higher risk protocols.

The primary caregivers for individuals with DD’s are often group

home staff and this can frequently result in the family being

overlooked in the medical treatment process. Family members are

occasionally present, but due to parental age, health and living

arrangements, parents are unable to be present for many visits.

Health care providers are strongly encouraged to contact the next of

kin to introduce themselves and obtain additional medical information.

Relatives are usually happy to hear from a medical provider and will

supply additional medical information. If family members express

interest in the treatment plan, they should be encouraged to be

present at office visits. This can be invaluable information, as the

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following account will describe. An individual with Autism and a history

of epilepsy was evaluated by a neurologist and was requested to

provide on-going neurological care. The patient was accompanied by a

staff member that has known the him for the 2 months he has resided

at the group home. A discharge summary from the developmental

center reported that were no seizures observed in the 4 years he

resided there. An EEG and MRI were unremarkable and the patient

was considered a relatively low risk for seizure relapse if the AED was

discontinued, based on this history. His legal guardian was a DDD

representative and the next of kin was a sister that resided in the next

state. The sister was contacted by phone at the time of the office visit

and she reported that over the past nine years, three separate

neurologists attempted to wean her nephew off Tegretol because he

had been seizure free for up to 4 years at a time. All three occasions

resulted in status epilepticus and during one hospitalization he

developed a severe pneumonia and required a prolong hospitalization.

The neurologist elected not pursue this option, the patient has been

followed for three years and continues to be seizure free on Tegretol.

Group Home Structure and Staff

Group home staff, sponsors and personal aids are of great importance

in the execution of the medical treatment plan for persons with DD’s.

A staff member will accompany the patient to the office and are often

times the only source of information at that time. Most persons

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relocating from developmental centers should have a brief medical

discharge summary. The level of experience, motivation and

competence of the staff varies significantly. Staff names should always

be noted in the margins of the chart adjacent to the medical note. This

will allow for tracking and resolving many problems. It will benefit the

health care provider to educate the accompanying staff and discuss

what is needed each visit. Community or agency presentations and “in-

services” can helpful in educating care providers.

Group home managers oversee the care and treatment of each

of the residents and are typically very reliable and dedicated. It may

be helpful to deal directly with manager on the more difficult to

manage individuals with epilepsy.

Physicians can develop a seizure record form that the staff must

complete after each seizure. The form can be tailored by the physician

to obtain pertinent information describing the event which will allow for

more accurate documentation of the number of seizures and

characterization of the seizure type. This type of form is especially

helpful since the staff member that witnessed a seizure may not be the

same staff that accompanies the patient to the office visit. This seizure

record form can be quickly reviewed at each visit. This will also allow

for a more accurate assessment of the current treatment and more

effective medication adjustments can be made. These seizure logs

should be kept in the person’s medical folder were the medication

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schedule and medical information is keep. The folder should

accompany the patient to the each visit.

Most group homes keep accurate medication records and log

books. In addition, many now have prescriptions filled at pharmacies

that offer “bubble packs”. Each dose is individually encased in a small

air bubble on a sheet with multiple rows of individual doses. After the

dose is given, a mark is made at the corresponding time in the

person’s medication log. This leaves much less chance of missed

doses. Not all group home staff is allowed to administer and dispense

medications. Each staff allowed to preform this duty must be “med

trained”.

Working within the regulations the group homes are mandated to

adhere to can be tedious and frustrating to those that are unfamiliar

with the requirements. The regulations are not established by the

group homes, but are state mandated, in an attempt to insure safety.

For example, on prescriptions the physician must write the specific

times medications are to be administered (i.e. q8am and 8pm) instead

of BID. Staff can not administer any medication without these specifics

and the prescription must be re-written. If doses are adjusted over the

phone, it must be followed by a written prescription that is mailed or

faxed so there is appropriate documentation at the group home. This is

problematic when these changes are made during on-call hours.

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Neurodiagnostic Testing

Persons with significant disabilities and cognitive impairment often do

not fully understand why they having a test performed. It is similar to a

child of the same mental age being unable to participate in a testing

situation. In addition, there is a higher incidence of psychological and

psychiatric conditions that compound the difficulty in obtaining these

studies. MRI of the brain requires the patient to lie very still for

approximately 40 minutes and several different forms of sedation

made are administered. This may simply include oral benzodiazepines

or require conscious sedation provided by the anesthesiologists. An

EEG can be significantly altered or suppressed with many of the

sedating medications, so the utility of this study is limited in some

cases. The determination of the seizure type would then have to be

based on the clinical description of the event, patient history and the

MRI.

Neurodiagnostic studies on our patients can be very time

consuming and often frustrating for busy MRI facilities and EEG labs.

Antiepileptic Medication

After the diagnosis of epilepsy and seizure type has been established,

the AED that is felt to be most effective with the least chance of side

effects is determined. This is based on whether the seizures are

primary generalized, partial, atonic or myoclonic. A careful review of

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the history is necessary to insure an AED that was used previously with

adverse effects is not reinstituted.

Co-morbid conditions and mode of drug delivery are prominent

issues in the DD. There is a higher incidence of behavioral and

psychiatric conditions in the DD population and AED’s are commonly

used as mood stabilizers to treat these conditions. Psychiatric co-

morbidities have been reported to occur in 25% and severe

maladaptive behavior in up to 55% of those meeting criteria for mental

retardation10. Depakote and Tegretol are the most commonly used

AED’s in the treatment of bipolar disorder, mania, intermittent

explosive disorder and in the management of aggressive behavior.

Therefore, when choosing a medication to treat seizures, the

psychiatric history must also be obtained. If a patient was previously

treated with Depakote or Tegretol as a mood stabilizer and it was

tolerated and effective, the same medication should be considered for

an initial anticonvulsant. This lowers the risk of adverse events since it

was previously tolerated and may also benefit behaviors. Conversely, a

previously documented adverse effect, such as agitation, would

dismiss a medication.

Tegretol (carbamazepine) is a first-line AED for partial onset and

some forms of generalized seizures. Tegretol is an excellent choice in

the treatment of individuals with DD’s because it has minimal adverse

effects on cognition and behavior. Tegretol is also indicated in the

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treatment of bipolar disorder and trigeminal neuralgia. It can be used

as a single agent to treat the relatively common co-morbidity of mood

disorder and epilepsy11. Adverse behavioral reactions occur

infrequently and may be due to the tricyclic ring structure in Tegretol.

This may result in mild mood elevating properties that would be

problematic in a patient with hypomania that has not been detected or

diagnosed. These patients may become agitated, irritable and

hyperactive. Hyponatremia is a known side effect and can be

exacerbated by patients who drink free water habitually or due to

dryness as a side effect of antidepressants or antipsychotics.

An additional advantage of Tegretol is the multiple formulations

available. The chewable tablets are used in patients unable to swallow

tablets and the extended release tablets allow for less frequent dosing.

Carbatrol is newer form of extended release carbamazepine that is

produced in a capsule that can be opened and sprinkled on food. This

has allowed the use of an extended release form in young children.

Depakote (valproate) is a major AED that has a broad spectrum

and is effective against primary generalized, partial, myoclonic

seizures and infantile spasms. Depakote is also indicated in the

treatment of mania and migraine headaches. Both of these conditions

commonly occur in patients with epilepsy. Additional uses in the DD

population include; behavioral cycling12, aggressive behaviors 13,14 and

hyperactivity/agitation in Autism15. This medication should be used in a

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very limited fashion or not at all in children under 2 years of age

because this group of patients has a significant risk of hepatotoxicity.

These patients are at even greater risk if they have a severe

developmental delay, are on additional AED’s or have a

neurometabolic disorder16. Thrombocytopenia is also a known side

effect and is rarely serious, however, if an individual’s DD includes

ataxia with frequent falls caution should be used. Depakote also is

available as a liquid, IV formulation that may be administered through

a gastric tube and sprinkle capsules.

Dilantin (phenytoin) has a very safe profile and is effective in the

treatment of partial and generalized seizures. There does not appear

to be any significant mood or behavioral effects. The advantage of

Dilantin is that it has a long half-life and may be given once a day. This

is helpful in those with compliance problems. It is available in liquid,

chewable and IV formulation. Dilantin is not a first choice AED in

person’s with DD because the side effect profile is especially

problematic in this population. Oral hygiene is commonly a significant

problem in individuals with DD and this is complicated by the known

side effect of gingival hyperplasia in Dilantin use. In addition,

individuals with DD are often susceptible to balance disturbances

which Dilantin can exacerbate17.

Phenobarbital is the oldest and one of the safest AED’s in current

use. It is the drug of choice on children under 2 years and is effective

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against a wide range of seizure types. It is not commonly used in older

patients because it has been shown to slow cognition and learning and

has adverse effects on mood, including irritability in children and

depression in adults18. However, it is a very good anticonvulsant and

there is patients that respond exceptionally well and is unable to be

changed to other AED’s.

Felbamate (Felabatol) was the first new generation AED and was

widely used and accepted until the post-marketing experience

revealed a high incidence of hepatic failure and aplastic anemia. It had

a favorable side effect profile for many patients with DD’s. It appeared

to have a mild stimulant quality and therefore was beneficial for

psychomotor slowing and reducing appetite. This same effect was

greater in a subgroup and resulted in insomnia and anorexia. Felbatol

has a wide spectrum of anticonvulsant activity and is especially

effective in Lennox-Gastaut syndrome. This medication should be used

only when the risk-benefit ratio has been carefully evaluated by all of

those involved in the person’s care.

Neurontin (Gabapentin) is effective as an adjunctive therapy in

partial seizures. It is widely used for neuropathic pain syndromes and

refractory bipolar disorder, but is only indicated for partial seizures.

Neurontin is available as a capsule only and has no serious medical

side effects. It has minimal protein binding and hepatic metabolism so

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it has minimal interactions with other medications and can be used

safely in other medical conditions.

Lamictal (Lamotrigine) also has a wide spectrum of

anticonvulsant activity, is effective against Lennox-Gastaut and

effective in monotherapy. Lamictal also appears to have a mild mood

elevating quality and is rarely sedating. It also has mood stabilizing

qualities and is being used in bipolar disorder. This combination gives

Lamictal a very favorable profile for the use in individuals with DD’s

19,20. However, there have been reports of adverse behavioral effects

including marked elevation of mood and agitation in this population of

patients 21,22.

Initially Lamictal was found to be causing a concerning number

of allergic reactions with subsequent development of Stevens-Johnson

syndrome. However, it has since been established that the incidence of

this reaction is directly related to the rate of titration. The slower the

rate of titration, the less likely a reaction will occur. There is little

chance of complications if increased by 2.5-5mg per week for children

and 12.5mg per week for adults. Lamictal is also available in chewable

tablets.

Topamax (Topiramate) is indicated for partial seizures and

Lennox-Gastaut syndrome. It has been very effective in difficult to

manage seizure disorders, is typically well tolerated and is effective in

monotherapy. Many studies have shown cognitive side effects and

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word finding difficulties. This has not been a significant problem in the

DD population. Topamax is also available in sprinkle formulation.

Gabitril (Tiagabine) is approved for adjunctive treatment of

partial seizures and has been associated with any behavioral effects.

Available in tablet forms only.

Sabril (vigabatrin) is not approved in this country and it may not

obtain approval. Changes in the white matter in animal studies and

concerns about visual field deficits may prevent its approval. It is

obtained from other countries and is effective and well tolerated in

persons with DD’s 23. Sabril has been most useful in the treatment of

infantile spasms.

Oxcabazepine (Trileptal) will be available soon. It is a variant of

carbamazepine, but metabolically bypasses the problematic epoxide

intermediate that is responsible for many of the side effects of

carbamazepine, including sedation. Patients are therefore able to

tolerate higher doses and this will result in a greater chance of

successful monotherapy. This should be very beneficial for use its use

in individuals with DD’s 24.

I feel reason there are so many conflicting reports concerning the

adverse behavioral effects of AED’s on DD person’s, is due to the fact

that we are unable to consistently recognize pre-existing psychiatric

disorders in handicapped individuals. This results in AED choice that

may not have been used if the condition was recognized and may

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aggravate a condition. In addition, DD persons often are unable

communicate side effects and may act out only when the side effects

are intolerable.

Individuals recently discharged from developmental centers are

may have had appropriate AED management. Epileptologist are

frequently contracted to aid in the management of patients with

epilepsy residing in developmental centers in New Jersey. This is not

true in all settings and some physicians in the community continue

AED’s indefinitely 25 . Re-evaluation of the patients epilepsy and need

for AED’s are frequently necessary. Monotherapy should be attempted

since it has been shown to be effective in up to 90% of institutionalized

persons with epilepsy 26,27. Withdrawing AED’s, especially Phenobarbital

can result in a marked improvement in alertness and mood. An

increase in muscle tone can be seen in some individuals with cerebral

palsy or acquired hemiplegia after Phenobarbital is withdrawn.

Baclofen is a good treatment for the spastically. Occasionally, an

unpleasant underlying personality or mood will be unmasked when the

AED is withdrawn. Mania can appear as Depakote or Tegretol are

withdrawn28. If there were no signs of side effects of the medication

that was withdrawn, it can simply be restarted to treat the unmasked

psychiatric disorder.

The field of developmental neurology is an evolving field of

study. It includes understanding both the unique medical needs of

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those with DD’s and the constraints involved in their medical care. Our

ability to successfully incorporate these unique provisions into current

clinical practice depends on the initiative, motivation and cooperation

we have as a medical community. Further collaborative studies are

required to determine the efficacy of alternative therapies, such as

vagal nerve stimulation 29,30 and epilepsy surgery 27 in individuals with

DD’s. Cooperation with diagnostic testing centers and educating our

communities is essential to the successful ongoing implementation of

appropriate neurological care to those with moderate to profound

DD’s.

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11. Waisburg H, Alvarez N. Carbamazepine in the treatment of epilepsy in people with intellectual disability. Journal of Intellectual Disability Research 1998;42(1):36-40.

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22. Beran RG, Gibson RJ. Aggressive behavior in intellectually challenged patients with epilepsy treated with lamotrigine. Epilepsia 1998;39(9):1018-1019.

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Table 1-1. Principles of AED therapyAssessment of risk/benefit ratio of starting medication Choosing appropriate medication based on seizure typeIf seizures persist, consider adding or substituting 2nd AED Diligently monitor for medication side effects and QOL

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