Literature Monitor

The Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society addressed seizure recurrence, immediate treatment with antiepileptic drugs (AEDs), and adverse events (AEs) related to AEDs in patients with an unprovoked first seizure. The risk of recurrence after an unprovoked first seizure is greatest within the first 2 years, especially in the first year. Immediate AED therapy after an unprovoked first seizure reduces the risk of seizure recurrence by approximately 35% within the subsequent 2 years; however, immediate treatment with AED is unlikely to improve sustained seizure remission over the longer term (>3 years). Adverse events associated with the immediate treatment of unprovoked first seizure with AEDs are predominantly mild and reversible, occurring in about 7% to 31% of patients.  

Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology. 2015;84(16):1705-1713. 

The Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society addressed seizure recurrence, immediate treatment with antiepileptic drugs (AEDs), and adverse events (AEs) related to AEDs in patients with an unprovoked first seizure. The risk of recurrence after an unprovoked first seizure is greatest within the first 2 years, especially in the first year. Immediate AED therapy after an unprovoked first seizure reduces the risk of seizure recurrence by approximately 35% within the subsequent 2 years; however, immediate treatment with AED is unlikely to improve sustained seizure remission over the longer term (>3 years). Adverse events associated with the immediate treatment of unprovoked first seizure with AEDs are predominantly mild and reversible, occurring in about 7% to 31% of patients.  

Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology. 2015;84(16):1705-1713. 

The Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society addressed seizure recurrence, immediate treatment with antiepileptic drugs (AEDs), and adverse events (AEs) related to AEDs in patients with an unprovoked first seizure. The risk of recurrence after an unprovoked first seizure is greatest within the first 2 years, especially in the first year. Immediate AED therapy after an unprovoked first seizure reduces the risk of seizure recurrence by approximately 35% within the subsequent 2 years; however, immediate treatment with AED is unlikely to improve sustained seizure remission over the longer term (>3 years). Adverse events associated with the immediate treatment of unprovoked first seizure with AEDs are predominantly mild and reversible, occurring in about 7% to 31% of patients.  

Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Neurology. 2015;84(16):1705-1713. 

WASHINGTON, DC—A new guideline found that administering an antiepileptic drug (AED) immediately after a first seizure reduces the risk of another seizure within two years. Announced at the 67th Annual Meeting of the American Academy of Neurology and published in the April 21 issue of Neurology, the evidence-based guideline was developed jointly by the American Academy of Neurology and the American Epilepsy Society.

“Determining whether to treat a patient after a first seizure is a complex process, but this guideline supports the use of medication in some cases and could influence standard practice for many physicians,” said lead author Allan Krumholz, MD, Professor of Neurology at the University of Maryland School of Medicine in Baltimore. “A single seizure could be a sign of epilepsy. Even one seizure is traumatic and can affect many aspects of an individual’s life from driving a car to employment options. This guideline clarifies when a person’s risk for another seizure warrants medication.”

One in 10 people worldwide have a first seizure in their lifetime. Annually, about 150,000 adults in the United States have an unprovoked seizure. In addition, one in 26 Americans will develop epilepsy. According to the International League Against Epilepsy, epilepsy is defined as one or more seizures with a high likelihood of recurrence, not due to another immediately triggering cause, such as low blood sugar.

The guideline authors reviewed nearly 50 studies on first seizure that addressed the probability that an adult with an unprovoked first seizure would have recurrent seizures, in addition to information about short- and long-term health risks and medication side effects.

The authors found strong evidence that for adults who have had a first seizure, the risk of another seizure is greatest within the first two years. The risk ranges from about a one-in-five chance (21%) to nearly a one-in-two chance (45%). They also found strong evidence that the risk of another seizure is greatest in those with a previous brain injury such as a stroke, brain tumor, or head trauma and in those with an EEG test result that shows signs of epilepsy. Their analysis revealed moderate evidence that the risk is greatest in people with a significant abnormality on brain imaging and in those who have nocturnal seizures.

According to the guideline, there is moderate evidence to suggest that immediate treatment with an AED lowers the risk of another seizure by 35% within the first two years. “About half of patients who have a first seizure will never have another seizure, but for the other half, immediate drug therapy may help,” Dr. Krumholz said. He stressed that the guideline should be used by physicians to help inform patients of their individual risk of a second seizure and involve them in the decision-making process.

The guideline cites moderate evidence suggesting that while treatment was shown to provide a short-term benefit, over the longer term (more than three years), treating a first seizure immediately rather than waiting for another seizure to occur is unlikely to increase or decrease the likelihood of remaining seizure free.

The guideline notes that 7% to 31% of patients who take an AED will experience a drug side effect; however, these are usually mild and can be reversed when a patient is switched to another AED or the dose is lowered.

“This guideline does not give a simple, black-and-white recommendation [about] whether an adult should immediately be started on an epilepsy drug,” said coauthor Jacqueline French, MD, a Professor of Neurology and Director of Translational Research at New York University’s Langone Comprehensive Epilepsy Center in New York City. “What is most important is that the decision whether to immediately treat a first seizure requires meaningful conversation between patient and doctor so that the patient’s individual circumstances, balance of risks and benefits, and personal preferences are understood and accounted for.”

The guideline was endorsed by the American Neurological Association and the World Federation of Neurology.

WASHINGTON, DC—A new guideline found that administering an antiepileptic drug (AED) immediately after a first seizure reduces the risk of another seizure within two years. Announced at the 67th Annual Meeting of the American Academy of Neurology and published in the April 21 issue of Neurology, the evidence-based guideline was developed jointly by the American Academy of Neurology and the American Epilepsy Society.

“Determining whether to treat a patient after a first seizure is a complex process, but this guideline supports the use of medication in some cases and could influence standard practice for many physicians,” said lead author Allan Krumholz, MD, Professor of Neurology at the University of Maryland School of Medicine in Baltimore. “A single seizure could be a sign of epilepsy. Even one seizure is traumatic and can affect many aspects of an individual’s life from driving a car to employment options. This guideline clarifies when a person’s risk for another seizure warrants medication.”

One in 10 people worldwide have a first seizure in their lifetime. Annually, about 150,000 adults in the United States have an unprovoked seizure. In addition, one in 26 Americans will develop epilepsy. According to the International League Against Epilepsy, epilepsy is defined as one or more seizures with a high likelihood of recurrence, not due to another immediately triggering cause, such as low blood sugar.

The guideline authors reviewed nearly 50 studies on first seizure that addressed the probability that an adult with an unprovoked first seizure would have recurrent seizures, in addition to information about short- and long-term health risks and medication side effects.

The authors found strong evidence that for adults who have had a first seizure, the risk of another seizure is greatest within the first two years. The risk ranges from about a one-in-five chance (21%) to nearly a one-in-two chance (45%). They also found strong evidence that the risk of another seizure is greatest in those with a previous brain injury such as a stroke, brain tumor, or head trauma and in those with an EEG test result that shows signs of epilepsy. Their analysis revealed moderate evidence that the risk is greatest in people with a significant abnormality on brain imaging and in those who have nocturnal seizures.

According to the guideline, there is moderate evidence to suggest that immediate treatment with an AED lowers the risk of another seizure by 35% within the first two years. “About half of patients who have a first seizure will never have another seizure, but for the other half, immediate drug therapy may help,” Dr. Krumholz said. He stressed that the guideline should be used by physicians to help inform patients of their individual risk of a second seizure and involve them in the decision-making process.

The guideline cites moderate evidence suggesting that while treatment was shown to provide a short-term benefit, over the longer term (more than three years), treating a first seizure immediately rather than waiting for another seizure to occur is unlikely to increase or decrease the likelihood of remaining seizure free.

The guideline notes that 7% to 31% of patients who take an AED will experience a drug side effect; however, these are usually mild and can be reversed when a patient is switched to another AED or the dose is lowered.

“This guideline does not give a simple, black-and-white recommendation [about] whether an adult should immediately be started on an epilepsy drug,” said coauthor Jacqueline French, MD, a Professor of Neurology and Director of Translational Research at New York University’s Langone Comprehensive Epilepsy Center in New York City. “What is most important is that the decision whether to immediately treat a first seizure requires meaningful conversation between patient and doctor so that the patient’s individual circumstances, balance of risks and benefits, and personal preferences are understood and accounted for.”

The guideline was endorsed by the American Neurological Association and the World Federation of Neurology.

WASHINGTON, DC—A new guideline found that administering an antiepileptic drug (AED) immediately after a first seizure reduces the risk of another seizure within two years. Announced at the 67th Annual Meeting of the American Academy of Neurology and published in the April 21 issue of Neurology, the evidence-based guideline was developed jointly by the American Academy of Neurology and the American Epilepsy Society.

“Determining whether to treat a patient after a first seizure is a complex process, but this guideline supports the use of medication in some cases and could influence standard practice for many physicians,” said lead author Allan Krumholz, MD, Professor of Neurology at the University of Maryland School of Medicine in Baltimore. “A single seizure could be a sign of epilepsy. Even one seizure is traumatic and can affect many aspects of an individual’s life from driving a car to employment options. This guideline clarifies when a person’s risk for another seizure warrants medication.”

One in 10 people worldwide have a first seizure in their lifetime. Annually, about 150,000 adults in the United States have an unprovoked seizure. In addition, one in 26 Americans will develop epilepsy. According to the International League Against Epilepsy, epilepsy is defined as one or more seizures with a high likelihood of recurrence, not due to another immediately triggering cause, such as low blood sugar.

The guideline authors reviewed nearly 50 studies on first seizure that addressed the probability that an adult with an unprovoked first seizure would have recurrent seizures, in addition to information about short- and long-term health risks and medication side effects.

The authors found strong evidence that for adults who have had a first seizure, the risk of another seizure is greatest within the first two years. The risk ranges from about a one-in-five chance (21%) to nearly a one-in-two chance (45%). They also found strong evidence that the risk of another seizure is greatest in those with a previous brain injury such as a stroke, brain tumor, or head trauma and in those with an EEG test result that shows signs of epilepsy. Their analysis revealed moderate evidence that the risk is greatest in people with a significant abnormality on brain imaging and in those who have nocturnal seizures.

According to the guideline, there is moderate evidence to suggest that immediate treatment with an AED lowers the risk of another seizure by 35% within the first two years. “About half of patients who have a first seizure will never have another seizure, but for the other half, immediate drug therapy may help,” Dr. Krumholz said. He stressed that the guideline should be used by physicians to help inform patients of their individual risk of a second seizure and involve them in the decision-making process.

The guideline cites moderate evidence suggesting that while treatment was shown to provide a short-term benefit, over the longer term (more than three years), treating a first seizure immediately rather than waiting for another seizure to occur is unlikely to increase or decrease the likelihood of remaining seizure free.

The guideline notes that 7% to 31% of patients who take an AED will experience a drug side effect; however, these are usually mild and can be reversed when a patient is switched to another AED or the dose is lowered.

“This guideline does not give a simple, black-and-white recommendation [about] whether an adult should immediately be started on an epilepsy drug,” said coauthor Jacqueline French, MD, a Professor of Neurology and Director of Translational Research at New York University’s Langone Comprehensive Epilepsy Center in New York City. “What is most important is that the decision whether to immediately treat a first seizure requires meaningful conversation between patient and doctor so that the patient’s individual circumstances, balance of risks and benefits, and personal preferences are understood and accounted for.”

The guideline was endorsed by the American Neurological Association and the World Federation of Neurology.

Deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy showed sustained efficacy and safety in this long-term follow-up of the SANTE trial. This study shows that ANT stimulation was associated with seizure frequency reduction rate of 69% at 5 years. The study also reported that 16% of subjects were seizure-free for ≥6 months during the 5 years of follow-up. ANT stimulation was associated with a 34% serious device-related adverse event rate at 5 years.

Salanova V, Witt T, Worth R, et al; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug resistant partial epilepsy. Neurology. 2015;84(10):1017-1025.

Deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy showed sustained efficacy and safety in this long-term follow-up of the SANTE trial. This study shows that ANT stimulation was associated with seizure frequency reduction rate of 69% at 5 years. The study also reported that 16% of subjects were seizure-free for ≥6 months during the 5 years of follow-up. ANT stimulation was associated with a 34% serious device-related adverse event rate at 5 years.

Salanova V, Witt T, Worth R, et al; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug resistant partial epilepsy. Neurology. 2015;84(10):1017-1025.

Deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy showed sustained efficacy and safety in this long-term follow-up of the SANTE trial. This study shows that ANT stimulation was associated with seizure frequency reduction rate of 69% at 5 years. The study also reported that 16% of subjects were seizure-free for ≥6 months during the 5 years of follow-up. ANT stimulation was associated with a 34% serious device-related adverse event rate at 5 years.

Salanova V, Witt T, Worth R, et al; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug resistant partial epilepsy. Neurology. 2015;84(10):1017-1025.

In a cross-sectional study, one hundred patients with epilepsy on antiepileptic drug (AED) therapy were observed to determine adherence to treatment. Patients in the adherent group—65% of the population—were found to have significantly lower depression scores compared with the nonadherent group. Memory scores were not robustly correlated with adherence. The authors conclude that physicians should consider targeting patients with epilepsy and comorbid depression as they may be at a higher risk of nonadherence.

McAuley JW, Passen N, Prusa C, Dixon J, Cotterman-Hart S, Shneker BF. An evaluation of the impact of memory and mood on antiepileptic drug adherence. Epilepsy Behav. 2015;43:61-65.

In a cross-sectional study, one hundred patients with epilepsy on antiepileptic drug (AED) therapy were observed to determine adherence to treatment. Patients in the adherent group—65% of the population—were found to have significantly lower depression scores compared with the nonadherent group. Memory scores were not robustly correlated with adherence. The authors conclude that physicians should consider targeting patients with epilepsy and comorbid depression as they may be at a higher risk of nonadherence.

McAuley JW, Passen N, Prusa C, Dixon J, Cotterman-Hart S, Shneker BF. An evaluation of the impact of memory and mood on antiepileptic drug adherence. Epilepsy Behav. 2015;43:61-65.

In a cross-sectional study, one hundred patients with epilepsy on antiepileptic drug (AED) therapy were observed to determine adherence to treatment. Patients in the adherent group—65% of the population—were found to have significantly lower depression scores compared with the nonadherent group. Memory scores were not robustly correlated with adherence. The authors conclude that physicians should consider targeting patients with epilepsy and comorbid depression as they may be at a higher risk of nonadherence.

McAuley JW, Passen N, Prusa C, Dixon J, Cotterman-Hart S, Shneker BF. An evaluation of the impact of memory and mood on antiepileptic drug adherence. Epilepsy Behav. 2015;43:61-65.

Fear of surgery, ignorance of treatment options, and tolerance of symptoms are the primary responses found to influence treatment-decision making for patients with epilepsy who are eligible for surgical treatment. Researchers examined twelve papers that examined patient perceptions of epilepsy surgery and physician attitudes. The authors conclude that patient and physician treatment misperceptions can lead to undertreatment and serious health consequences.

Dewar SR, Pieters HC. Perceptions of epilepsy surgery: a systematic review and an explanatory model of decision-making. Epilepsy Behav. 2015;44C:171-178.

Fear of surgery, ignorance of treatment options, and tolerance of symptoms are the primary responses found to influence treatment-decision making for patients with epilepsy who are eligible for surgical treatment. Researchers examined twelve papers that examined patient perceptions of epilepsy surgery and physician attitudes. The authors conclude that patient and physician treatment misperceptions can lead to undertreatment and serious health consequences.

Dewar SR, Pieters HC. Perceptions of epilepsy surgery: a systematic review and an explanatory model of decision-making. Epilepsy Behav. 2015;44C:171-178.

Fear of surgery, ignorance of treatment options, and tolerance of symptoms are the primary responses found to influence treatment-decision making for patients with epilepsy who are eligible for surgical treatment. Researchers examined twelve papers that examined patient perceptions of epilepsy surgery and physician attitudes. The authors conclude that patient and physician treatment misperceptions can lead to undertreatment and serious health consequences.

Dewar SR, Pieters HC. Perceptions of epilepsy surgery: a systematic review and an explanatory model of decision-making. Epilepsy Behav. 2015;44C:171-178.

Researchers at the Cleveland Clinic Epilepsy Center developed nomograms to predict freedom from seizures and Engel score of 1 (eventual freedom from seizures) based on a development cohort of 846 patients who had resective surgery between 1996 and 2011. The nomograms were tested in an external validation cohort of 604 patients from 4 epilepsy surgery centers. If these nomograms are validated they could be used to predict seizure outcomes in patients eligible for epilepsy surgery.

Jehi L, Yardi R, Chagin K, et al. Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis. Lancet Neurol. 2015;14(3):283-290.

Researchers at the Cleveland Clinic Epilepsy Center developed nomograms to predict freedom from seizures and Engel score of 1 (eventual freedom from seizures) based on a development cohort of 846 patients who had resective surgery between 1996 and 2011. The nomograms were tested in an external validation cohort of 604 patients from 4 epilepsy surgery centers. If these nomograms are validated they could be used to predict seizure outcomes in patients eligible for epilepsy surgery.

Jehi L, Yardi R, Chagin K, et al. Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis. Lancet Neurol. 2015;14(3):283-290.

Researchers at the Cleveland Clinic Epilepsy Center developed nomograms to predict freedom from seizures and Engel score of 1 (eventual freedom from seizures) based on a development cohort of 846 patients who had resective surgery between 1996 and 2011. The nomograms were tested in an external validation cohort of 604 patients from 4 epilepsy surgery centers. If these nomograms are validated they could be used to predict seizure outcomes in patients eligible for epilepsy surgery.

Jehi L, Yardi R, Chagin K, et al. Development and validation of nomograms to provide individualised predictions of seizure outcomes after epilepsy surgery: a retrospective analysis. Lancet Neurol. 2015;14(3):283-290.

Researchers found that people with epilepsy are less likely to get the recommended amount of sleep or levels of physical activity compared with patients without epilepsy. The study examined data from the 2010 cross-sectional National Health Interview Survey and found that 22% of adults with active epilepsy smoked and only 35% with active epilepsy met the recommended physical activity guidelines. In addition, only half of patients with active epilepsy slept the recommended 7 or 8 hours each day.

Cui W, Zack MM, Kobau R, Helmers SL. Health behaviors among people with epilepsy—results from the 2010 National Health Interview Survey. Epilepsy Behav. 2015;44C:121-126.

Researchers found that people with epilepsy are less likely to get the recommended amount of sleep or levels of physical activity compared with patients without epilepsy. The study examined data from the 2010 cross-sectional National Health Interview Survey and found that 22% of adults with active epilepsy smoked and only 35% with active epilepsy met the recommended physical activity guidelines. In addition, only half of patients with active epilepsy slept the recommended 7 or 8 hours each day.

Cui W, Zack MM, Kobau R, Helmers SL. Health behaviors among people with epilepsy—results from the 2010 National Health Interview Survey. Epilepsy Behav. 2015;44C:121-126.

Researchers found that people with epilepsy are less likely to get the recommended amount of sleep or levels of physical activity compared with patients without epilepsy. The study examined data from the 2010 cross-sectional National Health Interview Survey and found that 22% of adults with active epilepsy smoked and only 35% with active epilepsy met the recommended physical activity guidelines. In addition, only half of patients with active epilepsy slept the recommended 7 or 8 hours each day.

Cui W, Zack MM, Kobau R, Helmers SL. Health behaviors among people with epilepsy—results from the 2010 National Health Interview Survey. Epilepsy Behav. 2015;44C:121-126.

In this meta-analysis, researchers analyzed body positions of 253 cases of sudden unexpected death in epilepsy (SUDEP), revealing that 73.3% of patients died in the prone position while 26.7% died in nonprone positions. In addition, all 11 cases of video-EEG-monitored SUDEP reported the prone position. In a subgroup of 88 SUDEP cases, the prone position was reported in 85.7% of cases of patients aged ≤40 years and 60% in patients >40 years. The authors suggest that prone position is a major risk factor for SUDEP, especially in patients aged ≤40 years.

Liebenthal JA, Wu S, Rose S, Ebersole JS, Tao JX. Association of prone position with sudden unexpected death in epilepsy. Neurology. 2015;84(7):703-709.

In this meta-analysis, researchers analyzed body positions of 253 cases of sudden unexpected death in epilepsy (SUDEP), revealing that 73.3% of patients died in the prone position while 26.7% died in nonprone positions. In addition, all 11 cases of video-EEG-monitored SUDEP reported the prone position. In a subgroup of 88 SUDEP cases, the prone position was reported in 85.7% of cases of patients aged ≤40 years and 60% in patients >40 years. The authors suggest that prone position is a major risk factor for SUDEP, especially in patients aged ≤40 years.

Liebenthal JA, Wu S, Rose S, Ebersole JS, Tao JX. Association of prone position with sudden unexpected death in epilepsy. Neurology. 2015;84(7):703-709.

In this meta-analysis, researchers analyzed body positions of 253 cases of sudden unexpected death in epilepsy (SUDEP), revealing that 73.3% of patients died in the prone position while 26.7% died in nonprone positions. In addition, all 11 cases of video-EEG-monitored SUDEP reported the prone position. In a subgroup of 88 SUDEP cases, the prone position was reported in 85.7% of cases of patients aged ≤40 years and 60% in patients >40 years. The authors suggest that prone position is a major risk factor for SUDEP, especially in patients aged ≤40 years.

Liebenthal JA, Wu S, Rose S, Ebersole JS, Tao JX. Association of prone position with sudden unexpected death in epilepsy. Neurology. 2015;84(7):703-709.

Postoperative seizure freedom could be predicted using an easily measurable seizure freedom score (SFS) according to researchers from the Cleveland Clinic Epilepsy Center. The SFS was calculated by compiling 4 predictive outcome indicators: preoperative seizure frequency, history of generalized tonic-clonic seizures, brain MRI, and epilepsy duration. In a study population of 466 patients, seizure freedom rates were directly correlated with SFS scores. The authors propose that this tool may be beneficial for estimation of surgical candidacy and will help with patient and family counseling.

Garcia Gracia C, Yardi R, Kattan MW, et  al. Seizure freedom score: a new simple method to predict success of epilepsy surgery. Epilepsia. 2015;56(3):359-365.

Postoperative seizure freedom could be predicted using an easily measurable seizure freedom score (SFS) according to researchers from the Cleveland Clinic Epilepsy Center. The SFS was calculated by compiling 4 predictive outcome indicators: preoperative seizure frequency, history of generalized tonic-clonic seizures, brain MRI, and epilepsy duration. In a study population of 466 patients, seizure freedom rates were directly correlated with SFS scores. The authors propose that this tool may be beneficial for estimation of surgical candidacy and will help with patient and family counseling.

Garcia Gracia C, Yardi R, Kattan MW, et  al. Seizure freedom score: a new simple method to predict success of epilepsy surgery. Epilepsia. 2015;56(3):359-365.

Postoperative seizure freedom could be predicted using an easily measurable seizure freedom score (SFS) according to researchers from the Cleveland Clinic Epilepsy Center. The SFS was calculated by compiling 4 predictive outcome indicators: preoperative seizure frequency, history of generalized tonic-clonic seizures, brain MRI, and epilepsy duration. In a study population of 466 patients, seizure freedom rates were directly correlated with SFS scores. The authors propose that this tool may be beneficial for estimation of surgical candidacy and will help with patient and family counseling.

Garcia Gracia C, Yardi R, Kattan MW, et  al. Seizure freedom score: a new simple method to predict success of epilepsy surgery. Epilepsia. 2015;56(3):359-365.

Levetiracetam monotherapy, controlled-release carbamazepine monotherapy, and lamotrigine monotherapy have similar efficacy among elderly adults with new-onset focal epilepsy, according to research published in the March issue of Epilepsia. Levetiracetam has superior tolerability in this population, however, compared with controlled-release carbamazepine. Lamotrigine’s tolerability may be between those of levetiracetam and carbamazepine.

“This randomized-controlled trial provides evidence supporting the use of levetiracetam as first-line treatment for elderly patients with new-onset focal epilepsy and points to the value of lamotrigine as an alternative [to levetiracetam],” said Konrad J. Werhahn, MD, Professor of Neurology at the University Medical Center of the Johannes Gutenberg University in Mainz, Germany.

Half of all newly occurring epileptic seizures are expected to occur in patients age 60 and older in 2020. Few trials have evaluated treatment options for these patients, however. Observational data suggesting that levetiracetam may be effective in this population prompted Dr. Werhahn and colleagues to conduct a comparative trial.

A Yearlong Maintenance Period
Between March 2007 and August 2011, the investigators randomized 361 patients to controlled-release carbamazepine, lamotrigine, or levetiracetam. Eligible participants were age 60 or older and had new-onset focal epilepsy. The researchers excluded patients with symptomatic seizures occurring less than two weeks after the onset of acute cerebral insults and patients previously treated with valproate within four weeks of screening.

During a six-week period, doses were titrated to initial target amounts of 400 mg/day of carbamazepine, 100 mg/day of lamotrigine, or 1,000 mg/day of levetiracetam. The investigators selected these doses based on previous studies in the elderly. A 52-week maintenance period followed the titration period. Dose adjustments were allowed during the maintenance period to address concerns about tolerability and seizure control. Patients were withdrawn if they did not tolerate doses within this range or if they had recurrent seizures despite receiving the maximum dose.

The trial’s primary outcome measure was the retention rate at week 58, as measured from day 1 of treatment. Secondary outcome measures included seizure-freedom rates at weeks 30 and 58, time to first seizure, and time to first drug-related adverse event.

Adverse Events Occurred Earlier With Carbamazepine
The retention rate at week 58 was 45.8% for carbamazepine, 55.6% for lamotrigine, and 61.5% for levetiracetam. Retention rates were significantly different for all groups. Logistic regression analysis suggested that the number of concomitant diseases influenced retention at week 58.

The researchers found no significant differences in rates of seizure freedom at week 30 or at week 58. The rate of seizure freedom at week 58 was 33.3% for carbamazepine, 38.5% for lamotrigine, and 42.6% for levetiracetam. The time to first seizure after randomization or after titration was similar between treatment arms.

The incidence of reported adverse events was similar between treatment groups. Most adverse events were of mild to moderate severity. The most common adverse events were dizziness, fatigue, and headache. Adverse events occurred earlier with carbamazepine than with the other drugs. Also, more discontinuations due to adverse events occurred in the carbamazepine group than in the other groups.

“To our knowledge, the present trial is the first prospective comparison of levetiracetam with the optimal and most widely used formulation (controlled-release) of carbamazepine in this population,” said Dr. Werhahn, who receives compensation for activities with UCB Pharma. “Average doses of the drugs during the trial were all lower than the predefined target doses (most notably for carbamazepine), and also lower than those recommended in the individual product labels. This [datum] supports the recommendation that initial dosing of epilepsy medication for elderly patients should be lower, with a slower titration schedule than that used in younger adults, to reduce the risk of tolerability issues.

Although the study was not powered for the inclusion of the lamotrigine arm, “clear differences were evident in the tolerability profiles of these drugs during the trial, suggesting that the differences in retention rates at week 58 were driven primarily by the drugs’ tolerability profiles, rather than their efficacy,” Dr. Werhahn concluded.

—Erik Greb

Levetiracetam monotherapy, controlled-release carbamazepine monotherapy, and lamotrigine monotherapy have similar efficacy among elderly adults with new-onset focal epilepsy, according to research published in the March issue of Epilepsia. Levetiracetam has superior tolerability in this population, however, compared with controlled-release carbamazepine. Lamotrigine’s tolerability may be between those of levetiracetam and carbamazepine.

“This randomized-controlled trial provides evidence supporting the use of levetiracetam as first-line treatment for elderly patients with new-onset focal epilepsy and points to the value of lamotrigine as an alternative [to levetiracetam],” said Konrad J. Werhahn, MD, Professor of Neurology at the University Medical Center of the Johannes Gutenberg University in Mainz, Germany.

Half of all newly occurring epileptic seizures are expected to occur in patients age 60 and older in 2020. Few trials have evaluated treatment options for these patients, however. Observational data suggesting that levetiracetam may be effective in this population prompted Dr. Werhahn and colleagues to conduct a comparative trial.

A Yearlong Maintenance Period
Between March 2007 and August 2011, the investigators randomized 361 patients to controlled-release carbamazepine, lamotrigine, or levetiracetam. Eligible participants were age 60 or older and had new-onset focal epilepsy. The researchers excluded patients with symptomatic seizures occurring less than two weeks after the onset of acute cerebral insults and patients previously treated with valproate within four weeks of screening.

During a six-week period, doses were titrated to initial target amounts of 400 mg/day of carbamazepine, 100 mg/day of lamotrigine, or 1,000 mg/day of levetiracetam. The investigators selected these doses based on previous studies in the elderly. A 52-week maintenance period followed the titration period. Dose adjustments were allowed during the maintenance period to address concerns about tolerability and seizure control. Patients were withdrawn if they did not tolerate doses within this range or if they had recurrent seizures despite receiving the maximum dose.

The trial’s primary outcome measure was the retention rate at week 58, as measured from day 1 of treatment. Secondary outcome measures included seizure-freedom rates at weeks 30 and 58, time to first seizure, and time to first drug-related adverse event.

Adverse Events Occurred Earlier With Carbamazepine
The retention rate at week 58 was 45.8% for carbamazepine, 55.6% for lamotrigine, and 61.5% for levetiracetam. Retention rates were significantly different for all groups. Logistic regression analysis suggested that the number of concomitant diseases influenced retention at week 58.

The researchers found no significant differences in rates of seizure freedom at week 30 or at week 58. The rate of seizure freedom at week 58 was 33.3% for carbamazepine, 38.5% for lamotrigine, and 42.6% for levetiracetam. The time to first seizure after randomization or after titration was similar between treatment arms.

The incidence of reported adverse events was similar between treatment groups. Most adverse events were of mild to moderate severity. The most common adverse events were dizziness, fatigue, and headache. Adverse events occurred earlier with carbamazepine than with the other drugs. Also, more discontinuations due to adverse events occurred in the carbamazepine group than in the other groups.

“To our knowledge, the present trial is the first prospective comparison of levetiracetam with the optimal and most widely used formulation (controlled-release) of carbamazepine in this population,” said Dr. Werhahn, who receives compensation for activities with UCB Pharma. “Average doses of the drugs during the trial were all lower than the predefined target doses (most notably for carbamazepine), and also lower than those recommended in the individual product labels. This [datum] supports the recommendation that initial dosing of epilepsy medication for elderly patients should be lower, with a slower titration schedule than that used in younger adults, to reduce the risk of tolerability issues.

Although the study was not powered for the inclusion of the lamotrigine arm, “clear differences were evident in the tolerability profiles of these drugs during the trial, suggesting that the differences in retention rates at week 58 were driven primarily by the drugs’ tolerability profiles, rather than their efficacy,” Dr. Werhahn concluded.

—Erik Greb

Levetiracetam monotherapy, controlled-release carbamazepine monotherapy, and lamotrigine monotherapy have similar efficacy among elderly adults with new-onset focal epilepsy, according to research published in the March issue of Epilepsia. Levetiracetam has superior tolerability in this population, however, compared with controlled-release carbamazepine. Lamotrigine’s tolerability may be between those of levetiracetam and carbamazepine.

“This randomized-controlled trial provides evidence supporting the use of levetiracetam as first-line treatment for elderly patients with new-onset focal epilepsy and points to the value of lamotrigine as an alternative [to levetiracetam],” said Konrad J. Werhahn, MD, Professor of Neurology at the University Medical Center of the Johannes Gutenberg University in Mainz, Germany.

Half of all newly occurring epileptic seizures are expected to occur in patients age 60 and older in 2020. Few trials have evaluated treatment options for these patients, however. Observational data suggesting that levetiracetam may be effective in this population prompted Dr. Werhahn and colleagues to conduct a comparative trial.

A Yearlong Maintenance Period
Between March 2007 and August 2011, the investigators randomized 361 patients to controlled-release carbamazepine, lamotrigine, or levetiracetam. Eligible participants were age 60 or older and had new-onset focal epilepsy. The researchers excluded patients with symptomatic seizures occurring less than two weeks after the onset of acute cerebral insults and patients previously treated with valproate within four weeks of screening.

During a six-week period, doses were titrated to initial target amounts of 400 mg/day of carbamazepine, 100 mg/day of lamotrigine, or 1,000 mg/day of levetiracetam. The investigators selected these doses based on previous studies in the elderly. A 52-week maintenance period followed the titration period. Dose adjustments were allowed during the maintenance period to address concerns about tolerability and seizure control. Patients were withdrawn if they did not tolerate doses within this range or if they had recurrent seizures despite receiving the maximum dose.

The trial’s primary outcome measure was the retention rate at week 58, as measured from day 1 of treatment. Secondary outcome measures included seizure-freedom rates at weeks 30 and 58, time to first seizure, and time to first drug-related adverse event.

Adverse Events Occurred Earlier With Carbamazepine
The retention rate at week 58 was 45.8% for carbamazepine, 55.6% for lamotrigine, and 61.5% for levetiracetam. Retention rates were significantly different for all groups. Logistic regression analysis suggested that the number of concomitant diseases influenced retention at week 58.

The researchers found no significant differences in rates of seizure freedom at week 30 or at week 58. The rate of seizure freedom at week 58 was 33.3% for carbamazepine, 38.5% for lamotrigine, and 42.6% for levetiracetam. The time to first seizure after randomization or after titration was similar between treatment arms.

The incidence of reported adverse events was similar between treatment groups. Most adverse events were of mild to moderate severity. The most common adverse events were dizziness, fatigue, and headache. Adverse events occurred earlier with carbamazepine than with the other drugs. Also, more discontinuations due to adverse events occurred in the carbamazepine group than in the other groups.

“To our knowledge, the present trial is the first prospective comparison of levetiracetam with the optimal and most widely used formulation (controlled-release) of carbamazepine in this population,” said Dr. Werhahn, who receives compensation for activities with UCB Pharma. “Average doses of the drugs during the trial were all lower than the predefined target doses (most notably for carbamazepine), and also lower than those recommended in the individual product labels. This [datum] supports the recommendation that initial dosing of epilepsy medication for elderly patients should be lower, with a slower titration schedule than that used in younger adults, to reduce the risk of tolerability issues.

Although the study was not powered for the inclusion of the lamotrigine arm, “clear differences were evident in the tolerability profiles of these drugs during the trial, suggesting that the differences in retention rates at week 58 were driven primarily by the drugs’ tolerability profiles, rather than their efficacy,” Dr. Werhahn concluded.

—Erik Greb