Antiepileptic Drugs (AED’S) Used In Those With Intellectual And Developmental Disabilities: For Better Or Worse? Part 3


How does one differentiate between all of these medications and choose which is best? How does the availability of generic AED’s impact upon these choices? How is an individual with IDD affected by AED’s?

Adults and children with Intellectual and Developmental Disabilities (IDD) commonly have a number of chronic health conditions which can affect their quality of life and activities of daily living. Cognitive impairment, language dysfunction, and challenging behaviors can either individually or, together, greatly impact an individual’s ability to function and live happy lives. Common health complications include spasticity, challenging behaviors, heart and pulmonary disease, as well as seizure disorders.

Often, adults with IDD have a number of different healthcare providers who manage these various health issues. Usually these include the primary care doctor, the neurologist, perhaps a physiatrist and epileptologist, along with several therapists to assist with behavior  disorders. The central issue in such cases is who is acting as the quarterback and who is assembling and analyzing all of the data and touch points associated with the myriad of therapies and interventions used in controlling seizures in those with intellectual disabilities. Because, unlike other populations, people with IDD often cannot tell you what is wrong or how they are feeling. It has been noted that many  individuals with IDD take a variety of different medications for a number of health difficulties and, on occasion, multiple medications for the same problem. A survey done a number of years ago noted that the average number of prescription medications taken by adults with IDD was nine. Another survey confirmed that once a second drug is prescribed, the probability of success in managing the seizure drops to 25 percent, and if a third medication is used, it drops to 3 percent—not very good odds.

Uncontrolled health complications can lead to an increase in morbidity and mortality. The healthcare practitioner’s goal and plan of care is to assess for the presence of a particular health problem, judge the severity of the problem, and then make a clinical judgment on the need and selection of appropriate therapies. The benefit of healthcare is dependent on the degree of the risk of various care and treatments versus the overall benefit that the care and treatment provides to the individual. Seizure disorders are a prime example of a common medical condition seen in those with IDD in which the concept of risk versus benefit is truly put to the test.

Potential risks and benefits of care are complicated in those with IDD due to the high rate of uncontrolled/refractory seizures and polypharmacy.

Seizures are very common because the brain in those with IDD had not developed normally, resulting in neuronal dysfunction. The location, severity, and type of neuronal dysfunction determines what type of seizure disorder the individual will have, as well as whether the individual is going to be refractory to medical, surgical, or biomechanical intervention. Individuals with IDD have a high rate of being refractory to these various therapies. One of the main reasons for this is due to the common associated diffuse neuronal injury.

Nonetheless, seizures need to be treated because of the risk to an individual’s health. A seizure which involves convulsions can lead to physical trauma with a fall, muscle breakdown, choking, loss of oxygen to the brain and other vital organs, as well as tongue laceration. A Drop Attack or Atonic seizure can also be associated with injury after the body instantaneously becomes limp, leading to physical trauma when the individual falls suddenly to the ground. Staring spells and confusional states are manifestations of either an Absence or Complex Partial seizure. These seizure types can also lead to potential injury if the person is involved in an activity that, if a moment of loss of focus occurs, will lead to trauma or harm. Seizures can also lead to long term difficulties with attention, memory and retrieval. The frequency, severity, duration, and circumstance in which the seizure occurs will help to determine the degree of risk to the individual. AED’s are used to reduce these risks but not to add their own complications and risks i.e., ADR’s (Adverse Drug Reactions), to exacerbate poor health or injury. ADR’s will be reviewed later in this article. Sudden Unexpected Death in Epilepsy (SUDEP) occurs more commonly in those whose seizures are not well controlled.

A seizure can affect an individual’s ability to interact with the environment. The seizure may keep them from participating in work, social gatherings, and may also create a negative perception about their abilities to be a part of society. An individual with seizures may have low self-esteem, which can further contribute to his or her problems and may create additional complications such as depression, anxiety and continued difficulty adapting to social norms. Moreover, seizures may lead to excess emergency room visits and hospitalizations. Various tests and monitoring often are required.

Mainstay medications for seizures have been around since the 1920’s, with the advent of Phenobarbital and then later with Dilantin (phenytoin) in the 1930’s. Tegretol (Carbamazepine and Depakote (Valproic acid) became available in the 1960’s. Benzodiazepines, including Klonopin, began to be used for seizures in the 1980’s. There were no further additional new seizure medications until the 1990’s until Felbatol (Felbamate) was released and then there was an explosion of research and development of newer seizure medications in the late 1990’s, and a number of newer seizure medications have come to market ever since. The newer antiepileptic drugs (AED) include Lamictal (Lamotrigine), Gabitril (Tiagabine) (Topamax (Topiramate), Keppra (Levetiracetam), Vimpat (Lacosamide),Sabril (Vigabratrin), Neurontin (Gabapentin), Lyrica (Pregabalin), and Trileptal (Oxcarbazepine). Onfi (Clobazam) and Banzel (Rufinamide) are also two additional new AED’s that have been approved for seizures associated with those with Lennox-Gastaut syndrome (LGS), a devastating form of epilepsy often manifested by an uncommon number of seizures a day. LGS is commonly associated with IDD and occurs in both children and adults.

Several other AED’s have also come onto the market. Some of these newer medications are once a day or long acting preparations of currently available AED’s. There are over 15 different AED’s available for usage by practitioners to help treat seizure disorders. More AED’s are in development and will be commercially available soon

How does one differentiate between all of these medications and choose which is best? How does the availability of generic AED’s impact upon these choices? How is an individual with IDD affected by AED’s, good or bad? These questions are all very important in being able to provide the best level of care but also helping prevent additional problems inadvertently, which can have significant negative consequences to the individual.

Neurologists are the most common health specialist that treats seizure disorders. The main goal of seizure management is to make an individual seizure-free. Unfortunately, a significant percentage of individuals with IDD are medically refractory and despite multiple trials of at least three different AED’s, many still have breakthrough seizures. Seizure surgery, the ketogenic diet, and the usage of the Vagus Nerve stimulator (VNS) can and do help, but individually only add a very small chance of stopping all seizures from occurring. In people with IDDF who are refractory to AED intervention, the VNS may be justified inasmuch as the overall risk is minimal. The VNS also does not have the complications associated with the use of several AED’s. Seizure surgery may end up being the best chance for some individuals in being able to stop their seizures from occurring. Many individuals will continue to take a number of AED’s in combination in an effort to “control” their seizures. Some of these AED’s used may be those that have a higher chance of affecting cognition or behavior, including Dilantin, Phenobarbital, Topamax, Keppra, and various benzodiazepines including Klonopin , Valium, and Ativan. Many of these medications may not cause difficulties and the benefits to the individual may be positive.

Neurologists pick and choose amongst the large number of available AED’s based on a number of factors including efficacy for a particular seizure type, side effect profile, need for monitoring blood, frequency of dosing, available formulations, availability of generics, mode of action, and whether the AED’s interact with other concomitant medications.

Certain AED’s have proven to be effective in partial seizures, general seizures, or both. Others have been proven to be as effective on their own; (monotherapy), or only effective and tested as add-on therapy. AED’s that appear to be effective for most types of seizures are considered to be “broad spectrum” AED’s. It is not uncommon for some with IDD and refractory seizures to be on several AEDs and still have seizures. This also presents a set of risks and challenges inasmuch as it has been documented that use of more than three AED’s adds very little benefit to the overall seizure control. To be most effective, AED’s not only have to be affective for the type of seizure, but the  dosage and level of medication must be high enough and appropriate enough for that individual. There are a number of factors which may affect this. Noncompliance in not reliably taking AED’s is a very common reason why seizures may still occur in an individual. Someone with IDD may at times be noncompliant due to concomitant challenging behaviors, or inconsistent care supports.

A frequent issue that comes up often in seizure management is the issue of whether brand or generics AED’s should be used. A brand AED is the medication that a pharmaceutical company promotes and has ownership over for many years after it is released; i.e. medication patent. A pharmaceutical company spends many years doing research and development of medications prior to their approval by the FDA and their release to the marketplace. Once the medication patent runs out, the medication is then available for generic pharmaceuticals to then begin manufacturing it and making available to the marketplace. The main difference between a brand and a generic mediation are its name, cost, and potential bioequivalence. The medications are always the exact same chemical—but what mainly affects the difference is the way in which the medication is made into a pill or capsule, coated, or bound together to enable it to stay together and not fall apart. These issues may in some way affect how the medication gets absorbed and eliminated once it is ingested. There may be an inherent variability in this process, which may affect, ultimately, how much medication gets into the body and reaches its much needed part of the body.

The FDA mandates that all generics must have 10 to 20 percent equivalence to the brand medication in this fashion; this is called bioequivalence. Can this difference be relevant to those with seizures? If an individual’s seizure control is effected by a 10 to 20 percent lowered level in the blood with inconsistency, then it is possible that to an individual, it may make a difference. If the blood level at times is higher, then possible toxicity may occur. These decisions are often difficult between patient and healthcare provider. Having seizure  control consistency, reliability, avoidance of possible toxicity versus costs and the challenges that most insurance companies will make to push both parties to choose the often less expensive generic . The vast majority of patients can have adequate control with usage of generics.

The list of side effects of AED’s can be quite long including sedation, confusion, agitation, skin reactions, and affects to kidney, blood, bone, and liver. Every AED is different in its risks for developing side effects or adverse drug reactions. The risks may be person-dependent, related to possible concomitant behavioral or cognitive difficulties. Concomitant usage of other AED’s and usage of other medications for the person’s other health conditions also can affect the chance of developing ADR’s. Aging may increase the chance of ADR’s because  metabolism is slowed. The kidney and liver function maybe less able to fully eliminate AED’s from the body and, often, AED’s may have prolonged duration of action which can lead to higher than prior AED levels and increase the chance of medication toxicities.

Individuals with IDD may have a reduced level of cognitive function, including level of alertness. All AED’s can cause side effects that may impair cognition and attention. If someone with IDD is made to be “slower” by medications, it may have dramatic affects on their ability to interact with their family, friends, support staff and, therefore, make it much more difficult for them to be involved and participate fully in many life activities. A complex and difficult situation would be to determine if some with IDD are experiencing these ADR’s. Often if  someone with IDD is having ADR’s, they would simply be able to communicate and describe how and what they were feeling.  Unfortunately, as mentioned earlier in this article, someone with IDD may not have the abilities to communicate and describe these often significant difficulties. The overt manifestation of some of these ADR’s may be changes in sleep habits, gait function, abilities to perform their ADL’s, as well as possible alterations in behavior. The support staff and families who really know the individual are in the best position to appreciate when abnormal personality or behavior changes are happening and therefore they must report these changes as soon as possible to the appropriate professional healthcare or mental health experts. Communication and respect for everyone’s opinion is paramount.

Challenging behaviors are very common in those with IDD. Impulsivity, agitation, self injurious behavior, psychotic behaviors can all be manifest in some with IDD. AED’s may worsen some of these behaviors. A change of behavior may be attributed to the persons with IDD rather than to the underlying illness or ADR. This bias is called diagnostic overshadowing. This situation can be made even worse when, instead of determining what other underlying problem is driving the change in behavior and correcting it, the health practitioner may instead choose to primary treat the behavior by adding or increasing psychiatric medication. This inappropriate usage of pharmacologics may further impair cognition and alertness. Individuals with autism may also have the same difficulties with AED’s and how their behavior is affected.

Seizures can be devastating to the individual. Trauma, long term affects of memory, reduction in life activities, as well as possible reduced life expectancy, can occur. The treatment of seizures is necessary, but it carries various potential risks. The ability to appreciate the risks versus the benefits of seizure care can be a fine balance that has to be carefully and thoughtfully reviewed over time. The value of using various medications, either by themselves or in combination with other AED’s or medications used for other health purposes, must be  continually monitored—not only by the healthcare providers, but also by the care support team and families involved. A discussion should occur that spells out the goals of seizure care, including the realistic expectations of seizure control in relation to the potential pitfalls that treatment can create. •

Seth M. Keller, MD is Immediate Past President of the American Academy of Developmental Medicine and Dentistry (AADMD ) and is also associated with Advocare Neurology of South Jersey, and Consultant to New Jersey State DD Centers , and Board member of The Arc of Burlington County, New Jersey.

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