The Effectiveness of Vigabatrin on Epilepsy - Term Paper Example

RESEARCH ON THE EFFECTIVENESS OF VIGABATRIN ON EPILEPSY: Prepared for: K. LaGrandeur, New York Institute of Technology Prepared by: Devi Patel, Student New York Institute of Technology November 30, 2010 Table of Contents 2 Executive Summary 3 Introduction 3 Research Methods 6 Results 6 1. Study 1: Infantile Spasms 6 2. Study 2 : Partial Epilepsy 7 3. Study 3: West Syndrome 8 4. Patient, doctor, and FDA approval 8 Conclusions 9 Glossary 10 Bibliography 11 Executive Summary Epilepsy affects about 45 million people worldwide. Just in the United States, the prevalence of epilepsy is approximately 6 to 8 per 1000 population and with a high incidence of approximately 26 to 40 per 100,000 person per year, with higher rates among infants and persons older than 60 years of age (French & Pedley 166). With these figures in mind and the general knowledge that epilepsy is a none curable disease that people will have deal with for the rest of their lives, pharmacologic treatment plays an important role in the treatment of controlling seizure episodes associated with the epilepsy. When a new medicine is prescribed, both doctors and patients look at not only the effective results but also the side effects. A patient is not going to want to be prescribed something that could have more negative side effects than positive results, just as a doctor would more often not risk the patient’s life with a medicine that could hurt them. In the past two decades innovations in the coming of newer epileptic drugs was passed by the Food and Drug Administration authority. These drugs that were studied clinically do not really impose better controlling effects against the classical drugs known in the market today. But these newer drugs that were given as monotherapy or combination therapy were cited to have lesser side effects which are most important to most patients who are actually suffering from undesirable side effects of such epilepsy drugs. And with the coming of newer drugs physicians and most especially patients and their relatives are given a great array of choices when it comes to pharmacologic treatment in controlling epilepsy especially with the seizure control. The only question left is whether which drug would suit every patient’s need and treatment. This report discusses Vigabatrin and its effectiveness for epilepsy. The data presented in the results lead to the conclusion that Vigabatrin, though has a few side effects, is an effective pharmacologic treatment especially in children with epilepsy than in adults. Introduction: This report presents my research on the effectiveness of Vigabatrin for epilepsy. The research was conducted by consulting internet articles, journal entries, and medical reports that prove the effectiveness of Vigabatrin in the control of seizure and other neurologic signs associated with epilepsy as backed up with different studies made. In order to have a successful treatment proper diagnosis is necessary especially in giving medications as part of the treatment plan. Physicians are to make sure that the medications given will be appropriate for the symptoms presented by a patient to properly target the control and not to give medications that would not address the issue. By this, the author of this research would like to present a brief history regarding epilepsy and seizure and why the need for control is necessary so as to present properly the effectiveness of Vigabatrin in controlling such symptoms associated with epilepsy. Epilepsy is a chronic neurological disorder that causes recurrent unprovoked spasms and seizures. [1] The seizures are signs of abnormal or excess neural activity and are usually presented as abnormal uncontrollable repeated flexion-extension movements of extremities that can be directly observed by witnesses and can be associated with other signs such as alterations or loss of consciousness, drooling of saliva, motor changes such as upward rolling of eyeballs and restlessness. Seizures are a symptom of a neurological problem such as epilepsy and there are other neurological problems that can cause seizure occurrence such as high fever, meningitis, toxins, chemical imbalances of glucose or electrolytes, stimulant overdose, massive sleep deprivation, and alcoholic withdrawal. These are examples of events that can provoke a seizure and so diagnosis on the cause of seizure is important to properly address the cause of a seizure (Ojemann). Also physicians will have a better direction on the proper treatment for such seizure recurrence and will not be directed wrongly in giving medications. It is not a disorder with a known cure; however, there are medical treatments to enable patients with the disorder to live as comfortable as possible and to assume activities of daily living independently free from symptoms of epilepsy particularly seizure recurrence. According to studies it is more common in children and in people over the age of 65. It is also common after major surgeries. A common strategy used to diagnose epilepsy is to determine whether the seizures start in one region of the brain and spreads or occurs in many areas of the brain at the same time. When the seizure starts in one area and spreads, it is in the localization-related class. These seizures also have the possibility of not spreading at all. The other class of epileptic seizures is the primary generalized seizures. These involve various parts of the brain at the same time from the start. It is in the primary generalized seizures that people often lose consciousness. Seizures can last anywhere from a few seconds to several minutes. There have been cases where people do not even realize they are having a seizure because it is so quick (Ojemann). About 10% of the population will have a seizure at least once in their lives without being diagnosed with epilepsy. This is because most seizures do not evolve into epilepsy. However, the risk of having epilepsy is higher after one seizure, especially in an adult. To specifically diagnose epilepsy, a doctor would have to look into the description of the event by an onlooker, other medical conditions, family history of epilepsy, history of head injury, any aftereffects, and any history of recurrent events. The doctor might also order an EEG, which is a scalp recording of brain activity, an MRI, which is brain imaging, or a CT scan, which is a computerized tomography (Ojemann). When epilepsy was first discovered as a disorder, the only treatment was cutting out the piece of the brain that was showing the abnormal activities. However, today there are many medications one can take to control the seizures. Only 30% of epileptic patients do not respond to any form of treatment. Surgery is still an option, but it is the last resort. Doctors will have to consider several factors before beginning treatment for epilepsy. Though the recurrent seizures are a serious and potentially dangerous problem, all medications have serious potential side effects. The medicine prescribed depends on the type of seizure. Sometimes, many medications are needed at once. Over the years, many possibly medications have been innovated to try to treat patients with epilepsy (Ojemann). There are two types of drugs for treating epilepsy. Neither of these types cures it fully. The two groups are broad-spectrum and narrow-spectrum. Broad-spectrum drugs show efficiency in both localized and generalized seizures. Narrow-spectrum drugs are generally effective in only localized seizures. Broad-spectrum drugs show efficiency in partial and generalized seizures, and narrow-spectrum drugs are generally effective in partial seizures with or without secondary generalizations. Lacosamide and Pragablin are narrow-spectrum drugs, and Rufinamide and Vigabatrin are broad-spectrum drugs (Asconape). With the vast selections of drugs to treat symptoms associated with epilepsy patients and physicians are given a variety of choices to choose from but this study will focus on Vigabatrin and its effectiveness in the treatment of symptoms of epilepsy. Vigabatrin is an antiepileptic drug that was synthesized in 1974 (Parisi). Vigabatrin is classified as an anticonvulsant used in combination with other medications to treat seizure disorders or epilepsy. This drug is proven to decrease the number of seizures in adults and children who have not been able to control their seizures with other treatment thus it is never really given as a first line of drug therapy to control seizures but comes as a backup for refractory cases. The FDA approved it for use for epilepsy in the United States in 2009. It is a broad-spectrum drug, which means it works for both generalized and localized seizures. The exact way Vigabatrin works is still unknown, though it is FDA approved. However, it is believed to inhibit the catabolism of the natural calming substance in the brain known as GABA (gamma-aminobutyric acid) by irreversibly inhibiting transaminase [2] (Seger). Vigabatrin also reduces GAGA reuptake activity. Both mechanisms increase the GABA concentrations in the brain believed to calm the brain and inhibits abnormal neural activity. This action results in increased levels of GABA in the central nervous system. According to a study there is no direct correlation between the serum concentration of the drug and the effectiveness of the drug. The duration of the drug effect is unique because it is actually dependent on the rate of the individual’s enzyme resynthesis rather than on the rate of elimination of the drug from the systemic circulation. By this, Vigabatrin is quite different from other agents where in monitoring serum levels are almost obsolete, because the drug is individually tailored to the patient’s physiology based on one’s GABA receptors (“Epilepsy Therapy Project”). Today Vigabatrin is a drug that is primarily considered for children, and infants than in adults. The company it is provided from, known for the brand Sabril, is already FDA approved for treatment of spasms in infants and in partial seizures in adults (Elsevier). To determine the efficiency of Vigabatrin, three studies will be presented, as will the FDA approval and patient and doctor acceptance. In one study, Vigabatrin is tested against another antiepileptic drug in infants that experience spasms. In the next study, it shows the results of patients with localized epilepsy that were tested with Vigabatrin. In the third study, Vigabatrin is given to children with West Syndrome, which is a generalized epileptic disorder in infants. Through the results of these studies, the efficiency of Vigabatrin can be determined. Research Methods: In order to evaluate the efficiency of Vigabatrin, the following methods were used. 1. To look at a study of Vigabatrin against another antiepileptic drug in infants, I went to a journal article. 2. To look at a study of Vigabatrin used for localized epilepsy, I went to medical journals. 3. To evaluate a study of the use of Vigabatrin in children with West Syndrome, I looked at clinical journals. 4. To determine FDA, patient, and doctor approval of Vigabatrin. I looked at medical reports of usage and journal articles of the FDA’s decision. Results This section contains my findings from my research. First, I provide information from a study done with infantile spasms. Then I discuss the effects of Vigabatrin in a partial or localized epilepsy study. Next, I present information about a study done with children with West Syndrome. Later, I discuss patient, doctor, and FDA approval of Vigabatrin. I. Study 1: Infantile Spasms In Pakistan, there was a study done with children who have epilepsy and were experiencing infantile spasms. These children could have started experiencing these spasms anywhere from 6 months to 4 years. There were 56 children used. They were split into two groups. One was given ACTH, which is another antiepileptic drug, and the other was given Vigabatrin. The study tested the initial response to the treatments and the relapse rate. As you can see in the graph, the initial response to Vigabatrin in the study was about 55%. The initial response to ACTH was 50%. In terms of relapse rates, Vigabatrin had 33.3%, and ACTH had 55.5%. This means that a few more children in one group reacted more positively from the beginning to Vigabatrin than ACTH. This also means that more children started experiences seizures again after treatment in the ACTH group. Some of the side effects seen in the Vigabatrin group, however, were fatigue, abnormal eyesight, depression, and nausea, which are all known possible side effects of Vigabatrin (Ibrahim). From this study, Vigabatrin and ACTH showed no significant difference in the initial treatment of infantile spasms. However, patients receiving ACTH showed 1.2 times relapse as compared to the group receiving Vigabatrin. Hence it is suggested from this study that Vigabatrin should be the initial drug of choice in patients presenting with infantile spasms. However, larger studies are also encouraged to validate the therapeutic trends observed from this study (Ibrahim). In a similar context on the effectiveness of Vigabatrin as mono therapy for infantile spasms, two multi-centered controlled studies were made. The first study made was to evaluate the safety and efficacy of vigabatrin in patients less than 2 years of age with new onset infantile spasm that included 221 numbers of patients. In this study high dose of vigabatrin was compared to low dose of vigabratin given to patients. Significant finding shows seventeen patients in the high-dose group achieved spasm freedom compared to 8 patients in the low-dose group (“Epilepsy Therapy Project”). The second study was a multi-centered, randomized, double-blind, placebo-controlled, parallel group study with 40 children studied. This study statistically showed significant difference in the overall percentage of reductions in spasms between the Vigabatrin group of 68.9% and the placebo group of 17%. Based on the results of such study Vigabatrin really achieves high efficacy in the control of infantile spasms (“Epilepsy Therapy Project”). II. Study 2: Partial Epilepsy In the second study, Vigabatrin was tested in patients with partial epilepsy. Partial epilepsy is another name for localized epilepsy. In this study, an unspecified amount of people with partial epilepsy were used. All the people in this study were part of the 30% that is known to not show any response to any given treatment. They were all given Vigabatrin. There was about 50% reduction in seizures of the patients who were given Vigabatrin. Some still showed no sign of response. However, those who did show response had about 50% less side effects. Some people had many side effects, like abnormal eyesight, dizziness, weight loss, or depression. They also looked at previous studies with Epilepsy to compare their results and found that it was a recurrent trait of Vigabatrin use in partial epilepsy (Hemming). To establish the effectiveness of vigabatrin as an indication of adjunctive treatment for complex partial seizures in adults several other studies were made. This indication is based on numerous prospective, double-blind, placebo-controlled trials, in which its efficacy has been clearly demonstrated. Results of clinical trials shows positive response rates of ≥50% as observed in a study with 24%–67% of patients. Within these studies, subject retention rates were equivalent or superior to rates reported with other anti epileptic drugs, which indicates that vigabatrin therapy is well tolerated (Tolman & Faulkner). III. Study 3: West Syndrome This study was to observe the effects of Vigabatrin in children with West Syndrome. West Syndrome is an epileptic disorder in children that causes disturbances in development. These children experience generalized seizures from as young as six months old. This means that the seizure occurs in many parts of the brain often for several minutes. This could cause problems in development at such a young age. In this study children with West Syndrome were given this drug to see if development could be normal. What they found is that it caused many side effects: the worst of which includes abnormal eyesight. Some children went blind. They deduced that this drug is not efficient to give to children. In a study made on vigabratin by Fejerman et al (2000) designed to evaluate the efficacy and safety of vigabatrin as first-choice monotherapy in infants with West syndrome. One hundred sixteen patients with age range from 17 to 40 months with newly diagnosed West syndrome were studied in Argentina, from June 1994 to April 1998. The study showed freedom form seizure event at 61.8% of cases for cryptogenic and 29.3% for symptomatic West syndrome cases and more than 75% reduction in the number of infantile spasm. According to the study the most effective dose of vigabatrin was 150 mg/kg of body weight per day and the most frequent adverse events were somnolence in 19 cases and irritability in 15 cases however none was mentioned about visual acuity disturbance in the study which was said to be the most dangerous side effect of the drug (Fejerman et al). IV. Patient, doctor, and FDA approval The drug was synthesized in 1974 in Europe. However, it was not supplemented in the United States until 2009. In 2009, the FDA approved Sabril to produce this drug for use with epilepsy. Today it is not used too often because it was just approved in medical time. Doctors are not yet comfortable with this drug. However, patients can request it and it is being requested by patients more often. The reason doctors are not yet comfortable with it is because it was only approved a little over a year ago and although there are studies in Europe, there are not many in the United States. One main reason for the limited use of vigabatrin today might be associated with vision impairment. Vigabatrin is recommended as first line of therapy for infantile spasms and maybe parents as well as physicians would not take the risk of developing blindness that might come along with the effectiveness of the drug in seizure control since visual acuity is really hard to assess in children of young ages. Because of this risk, the FDA recommended that the drug will have a boxed warning regarding the risk of a progressive loss of peripheral vision with potential decrease in visual acuity. Also periodic vision testing is required for those taking Vigabatrin. Because of the risk of permanent vision damage, the drug will be available only through a restricted distribution program (United States Food and Drug Administration). Conclusion In my opinion, Vigabatrin is efficient in treating epilepsy. Although there are risks, every drug has risks with side effects. In this case, I think that the benefits outweigh the risks. If you or your child has epilepsy, you’re going to want to do whatever you can to allow yourself or your child to have a more comfortable a life as possible. Although there aren’t many tests done in the U.S. about it, there are quite a few in Europe and it had been used there since 1974. Although the side effects may seem scary, it is not everyone who experiences these side effects. Thusly, I believe that Vigabatrin is an efficient treatment medication for epilepsy (Elsevier). Indeed there is no doubt that Vigabratin is an excellent anticonvulsant medication for patients especially for patients with intractable complex partial seizure and for children with infantile spasms. The series of studies presented in this research can attest to the efficacy of Vigabatrin in treating epilepsy. However, in order to maximize the use of this drug is to follow the recommendations of its use especially by the FDA. Since most drugs include undesirable minor and sometimes major side effects, the desirable effect of the drug should be considered mostly against its side effects. In the case of vigabatrin, visual field constriction as the most common undesirable side effect should be religiously monitored and is something that all patients and their caregivers should be aware of especially for young children. The risk need only be accepted by patients in whom the drug does substantially improve seizure control (Wheless et al 353). With all these studies made on the efficacy of vigabatrin and the guidelines promulgated by the FDA, therefore it is concluded that the use of this potent drug to control seizure is established as an effective therapy in control of epilepsy. Glossary 1. A person with epilepsy will have uncontrollable jerking movements often with no cause. 2. GABA is the main neurotransmitter in our brains. The drug is believed to slow down this transmitter. Work Cited Asconape, J. (2010). The Selection of Antiepileptic Drugs for the Treatment of Epilepsy in Children and Adults. Neurological Clinics. December 8, 2010. Epilepsy Therapy Project (2012 Accelerating New Therapies: Introduction of Sabril (Vigabatrin). April 4, 2012. Elsevier. (2009). Antiepileptic Sabril receives FDA approval. MD Consult. December 3, 2010. French J. & Pedley T. (2008) Initial Management of Epilepsy. The New England Journal of Medicine. 359:166-176. Print Hemming, K., Maguire, M., Hutton, J., Marson, A. (2009). Vigabatrin for refractory partial epilepsy. (2009). Cochrane Epilepsy Group. December 9, 2010. Ibrahim S. Gulab S. Ishaque S. Saleem T. (2010). Clinical profile and treatment of infantile spasms using vigabatrin and ACTH--a developing country perspective. BMC Pediatrics. December 3, 2010. Natalio Fejerman N., Cersósimo R., Caraballo R., Grippo J., Corral S., Martino R., Martino G., Aldao M., Caccia P., Retamero M., Macat M., Di Blasi M. & Adi J. (2000) Vigabatrin as a First-Choice Drug in the Treatment of West Syndrome. Journal of Child Neurology. 15 (3), pp. 161-165. Print Ojemann, J. (2009). Epilepsy. Access Science. McGraw-Hill, December 3, 2010. Parisi P, Bombardieri R, Curatolo P. (2010). Vigabatrin. MD Consult. December 4, 2010. Seger, D. (2007). Anticonvulsants. Shannon: Haddad and Winchesters Clinical Management of Poisoning and Drug Overdose. December 4, 2010. Tolman J. & Faulkner M. (2011) Treatment options for refractory and difficult to treat seizures: focus on vigabatrin. Therapeutic Clinical Risk Management. 7: 367–375. United States Food and Drug Administration. (2009) Sabril Approved by FDA to Treat Spasms in Infants and Epileptic Seizures. August 21, 2009 Wheless J., Willmore J., & Brumback R. (2009) Vigabtrin. Advanced Therapy in Epilepsy. Pmph Usa Ltd Series, pp. 349-353 INTEROFFICE MEMORANDUM TO: Professor K. LaGrandeur FROM: Devi Patel SUBJECT: Audience Analysis for Project 4 DATE: 12/15/10 PURPOSE: The purpose of this memo is to present an audience analysis of the person(s) that would read the research report that was created as a project for this class. The goal of the project was to analyze the effectiveness of a recent medical innovation. The topic chosen was Vigabatrin, a drug used for epilepsy. AUDIENCE DESCRIPTION: While writing this report, I imagined that there would be two groups of people that would be interested in it. The first would be doctors who might want to prescribe the medicine to patients. The second group would be people with epilepsy or friends and family of epileptic patients who are looking for a treatment that might possibly help them. I think both groups are likely to read the full report since Vigabatrin is a drug and could thusly have negative side effects. HOW THE AUDIENCE DESCRIPTION AFFECTED THE RESEARCH REPORT: I knew that the vocabulary would be difficult for some to understand, thusly, I added a glossary to help them. I also used smaller words in order to make it easier for non-medical people to understand. Read More