Should epilepsy patients ever stop taking anti-seizure drugs?

Should epilepsy patients ever stop taking anti-seizure drugs?

Medication can control seizures in about two-thirds of people with epilepsy. The drugs are not a cure, but seizures don't always last a lifetime; in as many as half of people with epilepsy, the seizures may stop on their own. This means there's a subset of people taking anti-seizure medication who don't need it. After years without seizures, many people want to try stopping their medication. Some of them will stay seizure free, and some won't. Predicting who might safely come off medication and who should continue taking it is part science, part art and part personal preference. Some believe that anyone diagnosed with epilepsy should take medication for the rest of their lifetime; others say it's clear that not all epilepsy is lifelong, and taking unnecessary medication for decades can be a physical, financial and psychological burden. "There is certainly a group that benefits from medication withdrawal. Who are those patients and how do we identify them?" asked K.P. Vinayan, from the Amrita Institute of Medical Sciences in Kerala. Vinayan spoke during a debate at the ILAE International Congress in Bangkok focused specifically on tapering medication in people with adult-onset focal epilepsy with a known cause. Alejandro De Marinis, University of Chile, represented the other side of the issue. "We have no idea when we should be taking someone off medication, or even if we should," he said. Roadblocks to research Because of the variety of epilepsy types and patient characteristics, studies on stopping medication tend to combine heterogenous groups. One study might include adult-onset and pediatric onset epilepsy, generalized and focal epilepsy, and adults and children. Randomized, double-blind studies-;while considered the gold standard of evidence-;are ethically compromising. Both physicians and people with epilepsy generally have strong opinions about whether to continue or stop medication, which could affect compliance. In addition, there's general agreement that certain subgroups of people with epilepsy need to continue their medication for life. Only two randomized studies about the effects of stopping medication have been completed; one also was double-blind. That study, known as the Akershus study, found that people whose medication was stopped (through gradual dose tapering) did not have a greater risk for seizures in the following year, compared with people who stayed on their medication. Of the group that stopped medication, 15% had seizures, compared with 7% of the group that continued. But because each group included only about 70 people, statistics showed that the difference in risk could have been due to chance (RR=2.46, 95% CI 0.85-7.08, p=0.095). The other randomized trial-;a 1991 study of 1,013 adults and children authored by the Medical Research Council (MRC)-;found that stopping medication increased the risk for seizures in the first 2 years: 41% of the group that stopped medication had at least one seizure, compared with 22% of the group that stayed on medication. After that time point, the difference between the groups equalized. A recent study from China focused specifically on people with adult-onset focal epilepsy. It categorized study participants by seizure-free period: 2 to 3 years, 3 to 4, 4 to 5, and more than 5. Unlike most studies, this one followed participants for up to 15 years after stopping medication. The research found that people with at least 5 years of seizure freedom before stopping the medication could stop taking medication without an increased risk for seizures. Those with less than 5 years of seizure freedom under their belts were at double to triple the risk for seizures if they stopped their medication, compared with a similar group who stayed on their prescriptions. In this study, most seizures happened during the first 4 years; in the group with 5 or more years of seizure freedom, most happened during the first 2 years. As a real-world cohort study lasting more than 10 years, this study provides evidence for patients who would like to consider withdrawing from medications after a long period of seizure freedom." Xinshi Wang, First Affiliated Hospital of Wenzhou Medical University She noted that seizure relapse rates were likely higher in this study than in most others, due to the study population. "Quite a proportion of adult-onset focal epilepsy is caused by focal lesions, whether detectable or undetectable," said Wang. "This will result in recurrent seizures if the lesions are not removed through surgery." Risks and benefits Study participants were not randomized; they chose whether to stop or continue medication. More than 80% decided to continue treatment. Other studies of patient preference have found similar skews; for example, a survey in Macedonia found that 55% of seizure-free adults preferred to stay on their anti-seizure medication. "Patients who have been seizure free for a long time are usually tolerant of the drugs they are taking," said Wang. "And some are afraid that a witnessed seizure would lead to job loss or put them in a dangerous situation." Wang said some people in the study may have been reluctant to stop medication because they had risk factors for seizure relapse, such as symptomatic epilepsy or abnormalities on EEG. On the other hand, some patients may strongly prefer to try stopping their medication, due to side effects, cost, or other issues. This is another reason why clinicians must keep an open mind, said Vinayan, as they need to be involved in the process. "If their physician is not willing to discuss this option with them, they may try to [stop taking medication] themselves," she said. "This can be dangerous." Who stays seizure free? Studies have found that between 34% and 88% of patients remained seizure free after stopping medication, which means that 12% to 66% had seizures. The wide range of estimates reflects diverse patient populations, study designs and follow-up times. Only 15% of people had seizures in the Akershus study; however, that figure comes from the first year of follow-up. The study also had strict criteria that excluded people with certain risk factors for seizure relapse, such as juvenile myoclonic epilepsy or generalized epilepsy with abnormal EEG, as well as anyone taking more than one anti-seizure medication. Over the years, studies have identified at least 25 factors associated with seizure risk after stopping medication. Eleven are included in an online risk estimator for health professionals. Based on a 2017 meta-analysis, the calculator estimates seizure risk two years and five years after medication is stopped. Regaining seizure freedom



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