Epilepsy Resource Center

NEW ORLEANS – Bioequivalent generic formulations of levetiracetam and lamotrigine reduced seizures by a similar extent over 2 years in a retrospective study of patients with newly diagnosed focal epilepsy.

Michele G. Sullivan/MDedge News

Each drug had a specific adverse event profile, with lamotrigine associated with rash and levetiracetam with mood disorders, Sirichai Chayasirisobhon, MD, said at the annual meeting of the American Epilepsy Society. This finding can play into the initial therapeutic decision, said Dr. Chayasirisobhon of Kaiser Permanente Southern California. “If someone comes in with depression or mood disorder, I will start on lamotrigine, not levetiracetam. And we can decrease the chance of rash with a very slow titration, as we did here, starting with just 5 mg/kg and working up over 6 months.”

Although the drugs have a somewhat similar teratogenic profile, Dr. Chayasirisobhon added that he favors lamotrigine for women of childbearing years. “It’s a little bit better choice for them I think.”

His retrospective analysis followed 442 patients from first seizure and medical therapy for 2 years. The generic medications came from Kaiser Permanente’s central pharmacy. They were single-source, with a proven 95% bioequivalence. The main outcome was the percentage of patients who became seizure free and remained so. Any seizure, whether febrile, breakthroughs, or from titration, was considered a failure. These patients were dropped from the study. Any patient who developed a drug-related rash was dropped from the study and started on another medication.


More women than men took lamotrigine (113 vs. 75), whereas more men took levetiracetam (148 vs. 106). Those taking lamotrigine were younger than were those taking levetiracetam (30 vs. 40 years).

At the end of 2 years, there was no statistically significant difference in the primary outcome of being free from seizures (66.5% with lamotrigine vs. 72.4% with levetiracetam). In the lamotrigine group, 33.5% were eliminated from the study, 24% because they had a seizure, and the rest due to an adverse event. In the levetiracetam group, 27.6% were eliminated, 13% because they had a seizure and the rest because of an adverse event.

Adverse events in the lamotrigine group included rash (12), dizziness (3), lethargy (1), and mood changes (2). Among the levetiracetam group, adverse events included dizziness (3), lethargy (7), mood changes (20), slowed thinking (4), depression (2) and headache (1).

“Rash was the main event we saw in this group, and this was even when we did a very slow titration of 5 mg/kg per week,” Dr. Chayasirisobhon said. “Any sign of rash or itching at all, we told them to stop immediately and call us. Fortunately, we had no cases of Steven-Johnson syndrome and all our cases of rash were transient. But in the levetiracetam group, the mood changes are the major thing. Some of the patients became very agitated and aggressive. Whenever we see a patient for the first time, we always ask about mood changes, and we instruct the family to call and report any changes in mood immediately.”

Aside from reproductive age, however, Dr. Chayasirisobhon generally prefers to start new patients on levetiracetam. Its safety profile is remarkable, he said, recounting a case report he published in 2010 (Acta Neurol Taiwan. 2010;19:292-5).

The paper describes a male patient who decided to commit suicide after an argument with his wife. He took his levetiracetam and walked to his father’s grave, swallowing pills the entire time. When he arrived at the grave, he had taken around 65 grams of the medication. “The amazing thing was, he’s still walking, just a little unsteady. Then he decided he’s not ready to die,” Dr. Chayasirisobhon said. “He was able to call 911, so he’s still talking fine. When they checked his level it was so high, but he remained unimpaired except for the unsteady gait and some nystagmus.”

The study did not receive outside funding. Dr. Chayasirisobhon had no financial disclosures.

[email protected]

SOURCE: Chayasirisobhon S et al. AES 2018, Abstract 2.147

NEW ORLEANS – Bioequivalent generic formulations of levetiracetam and lamotrigine reduced seizures by a similar extent over 2 years in a retrospective study of patients with newly diagnosed focal epilepsy.

Michele G. Sullivan/MDedge News

Each drug had a specific adverse event profile, with lamotrigine associated with rash and levetiracetam with mood disorders, Sirichai Chayasirisobhon, MD, said at the annual meeting of the American Epilepsy Society. This finding can play into the initial therapeutic decision, said Dr. Chayasirisobhon of Kaiser Permanente Southern California. “If someone comes in with depression or mood disorder, I will start on lamotrigine, not levetiracetam. And we can decrease the chance of rash with a very slow titration, as we did here, starting with just 5 mg/kg and working up over 6 months.”

Although the drugs have a somewhat similar teratogenic profile, Dr. Chayasirisobhon added that he favors lamotrigine for women of childbearing years. “It’s a little bit better choice for them I think.”

His retrospective analysis followed 442 patients from first seizure and medical therapy for 2 years. The generic medications came from Kaiser Permanente’s central pharmacy. They were single-source, with a proven 95% bioequivalence. The main outcome was the percentage of patients who became seizure free and remained so. Any seizure, whether febrile, breakthroughs, or from titration, was considered a failure. These patients were dropped from the study. Any patient who developed a drug-related rash was dropped from the study and started on another medication.


More women than men took lamotrigine (113 vs. 75), whereas more men took levetiracetam (148 vs. 106). Those taking lamotrigine were younger than were those taking levetiracetam (30 vs. 40 years).

At the end of 2 years, there was no statistically significant difference in the primary outcome of being free from seizures (66.5% with lamotrigine vs. 72.4% with levetiracetam). In the lamotrigine group, 33.5% were eliminated from the study, 24% because they had a seizure, and the rest due to an adverse event. In the levetiracetam group, 27.6% were eliminated, 13% because they had a seizure and the rest because of an adverse event.

Adverse events in the lamotrigine group included rash (12), dizziness (3), lethargy (1), and mood changes (2). Among the levetiracetam group, adverse events included dizziness (3), lethargy (7), mood changes (20), slowed thinking (4), depression (2) and headache (1).

“Rash was the main event we saw in this group, and this was even when we did a very slow titration of 5 mg/kg per week,” Dr. Chayasirisobhon said. “Any sign of rash or itching at all, we told them to stop immediately and call us. Fortunately, we had no cases of Steven-Johnson syndrome and all our cases of rash were transient. But in the levetiracetam group, the mood changes are the major thing. Some of the patients became very agitated and aggressive. Whenever we see a patient for the first time, we always ask about mood changes, and we instruct the family to call and report any changes in mood immediately.”

Aside from reproductive age, however, Dr. Chayasirisobhon generally prefers to start new patients on levetiracetam. Its safety profile is remarkable, he said, recounting a case report he published in 2010 (Acta Neurol Taiwan. 2010;19:292-5).

The paper describes a male patient who decided to commit suicide after an argument with his wife. He took his levetiracetam and walked to his father’s grave, swallowing pills the entire time. When he arrived at the grave, he had taken around 65 grams of the medication. “The amazing thing was, he’s still walking, just a little unsteady. Then he decided he’s not ready to die,” Dr. Chayasirisobhon said. “He was able to call 911, so he’s still talking fine. When they checked his level it was so high, but he remained unimpaired except for the unsteady gait and some nystagmus.”

The study did not receive outside funding. Dr. Chayasirisobhon had no financial disclosures.

[email protected]

SOURCE: Chayasirisobhon S et al. AES 2018, Abstract 2.147

NEW ORLEANS – Bioequivalent generic formulations of levetiracetam and lamotrigine reduced seizures by a similar extent over 2 years in a retrospective study of patients with newly diagnosed focal epilepsy.

Michele G. Sullivan/MDedge News

Each drug had a specific adverse event profile, with lamotrigine associated with rash and levetiracetam with mood disorders, Sirichai Chayasirisobhon, MD, said at the annual meeting of the American Epilepsy Society. This finding can play into the initial therapeutic decision, said Dr. Chayasirisobhon of Kaiser Permanente Southern California. “If someone comes in with depression or mood disorder, I will start on lamotrigine, not levetiracetam. And we can decrease the chance of rash with a very slow titration, as we did here, starting with just 5 mg/kg and working up over 6 months.”

Although the drugs have a somewhat similar teratogenic profile, Dr. Chayasirisobhon added that he favors lamotrigine for women of childbearing years. “It’s a little bit better choice for them I think.”

His retrospective analysis followed 442 patients from first seizure and medical therapy for 2 years. The generic medications came from Kaiser Permanente’s central pharmacy. They were single-source, with a proven 95% bioequivalence. The main outcome was the percentage of patients who became seizure free and remained so. Any seizure, whether febrile, breakthroughs, or from titration, was considered a failure. These patients were dropped from the study. Any patient who developed a drug-related rash was dropped from the study and started on another medication.


More women than men took lamotrigine (113 vs. 75), whereas more men took levetiracetam (148 vs. 106). Those taking lamotrigine were younger than were those taking levetiracetam (30 vs. 40 years).

At the end of 2 years, there was no statistically significant difference in the primary outcome of being free from seizures (66.5% with lamotrigine vs. 72.4% with levetiracetam). In the lamotrigine group, 33.5% were eliminated from the study, 24% because they had a seizure, and the rest due to an adverse event. In the levetiracetam group, 27.6% were eliminated, 13% because they had a seizure and the rest because of an adverse event.

Adverse events in the lamotrigine group included rash (12), dizziness (3), lethargy (1), and mood changes (2). Among the levetiracetam group, adverse events included dizziness (3), lethargy (7), mood changes (20), slowed thinking (4), depression (2) and headache (1).

“Rash was the main event we saw in this group, and this was even when we did a very slow titration of 5 mg/kg per week,” Dr. Chayasirisobhon said. “Any sign of rash or itching at all, we told them to stop immediately and call us. Fortunately, we had no cases of Steven-Johnson syndrome and all our cases of rash were transient. But in the levetiracetam group, the mood changes are the major thing. Some of the patients became very agitated and aggressive. Whenever we see a patient for the first time, we always ask about mood changes, and we instruct the family to call and report any changes in mood immediately.”

Aside from reproductive age, however, Dr. Chayasirisobhon generally prefers to start new patients on levetiracetam. Its safety profile is remarkable, he said, recounting a case report he published in 2010 (Acta Neurol Taiwan. 2010;19:292-5).

The paper describes a male patient who decided to commit suicide after an argument with his wife. He took his levetiracetam and walked to his father’s grave, swallowing pills the entire time. When he arrived at the grave, he had taken around 65 grams of the medication. “The amazing thing was, he’s still walking, just a little unsteady. Then he decided he’s not ready to die,” Dr. Chayasirisobhon said. “He was able to call 911, so he’s still talking fine. When they checked his level it was so high, but he remained unimpaired except for the unsteady gait and some nystagmus.”

The study did not receive outside funding. Dr. Chayasirisobhon had no financial disclosures.

[email protected]

SOURCE: Chayasirisobhon S et al. AES 2018, Abstract 2.147

Unplanned pregnancy among women with epilepsy is associated with twice the risk of spontaneous fetal loss (SFL) when compared with women with epilepsy who planned their pregnancy, according to results from a retrospective study published online ahead of print October 15 in JAMA Neurology.

“This analysis adds the finding that unplanned pregnancy may increase the risk of SFL in women with epilepsy and identifies pregnancy planning, maternal age, and interpregnancy interval as significant modifiable variables,” said Andrew G. Herzog, MD, a neurologist at the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center in Wellesley, Massachusetts, and colleagues.

The Epilepsy Birth Control Registry

The researchers examined results from a web-based survey completed by 1,144 women in the Epilepsy Birth Control Registry (EBCR) between 2010 and 2014. Respondents provided data on contraception use, pregnancy history, and antiepileptic drug (AED) treatment. Patients were between ages 18 and 47 (mean, 28.5). Approximately 8.7% of the cohort were minorities, and 39.8% had household incomes of $25,000 or less.

Pregnancy history data included number of pregnancies, number of planned or unplanned pregnancies, AED type used during pregnancies, and pregnancy outcomes such as live birth, induced abortion, and SFL. Patients were categorized as receiving no therapy, monotherapy, or polytherapy. AED use was further subdivided into no AED, enzyme-inducing AED, non–enzyme-inducing AED, enzyme-inhibiting AED, glucuronidated AED, and mixed.

Most Pregnancies Were Unplanned

Of 794 pregnancies, 530 (66.8%) were unplanned and 264 (33.2%) were planned. Outcomes included 473 live births (59.6%), 141 induced abortions (17.8%), and 180 SFLs (22.7%). Among patients who did not have an induced abortion, SFL risk was higher if the pregnancy was unplanned (137 patients, 35.0%), compared with planned (43 patients, 16.4%) The risk ratio (RR) of SFL was 2.14. According to a regression analysis, SFL risk was higher for patients where “planning was entered alone” in unplanned pregnancies (odds ratio [OR], 2.75), as well as when adjusted for AED category, maternal age, and interpregnancy interval (OR, 3.57).

There was an association between maternal age (OR, 0.957) and risk of SFL. Risk was lower in the 18- to 27-year-olds (118 patients; 29.5%; RR, 0.57) and 28- to 37-year-olds (44 patients; 20.8%; RR, 0.40), compared with the under-18 group (15 patients, 51.7%). Risk of SFL was related to interpregnancy interval (OR, 2.878). This risk was greater if the interpregnancy interval was under one year (56 patients, 45.9%), compared with one year (56 patients, 22.8%) or higher (RR, 2.02).

The Epilepsy Foun-dation and Lundbeck funded the study. Dr. Herzog reports grants, and two coauthors received salary support from grants, from the two organizations.

—Jeff Craven

Suggested Reading

Herzog AG, Mandle HB, MacEachern DB. Association of unintended pregnancy with spontaneous fetal loss in women with epilepsy: findings of the Epilepsy Birth Control Registry. JAMA Neurol. 2018 Oct 15 [Epub ahead of print].

Unplanned pregnancy among women with epilepsy is associated with twice the risk of spontaneous fetal loss (SFL) when compared with women with epilepsy who planned their pregnancy, according to results from a retrospective study published online ahead of print October 15 in JAMA Neurology.

“This analysis adds the finding that unplanned pregnancy may increase the risk of SFL in women with epilepsy and identifies pregnancy planning, maternal age, and interpregnancy interval as significant modifiable variables,” said Andrew G. Herzog, MD, a neurologist at the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center in Wellesley, Massachusetts, and colleagues.

The Epilepsy Birth Control Registry

The researchers examined results from a web-based survey completed by 1,144 women in the Epilepsy Birth Control Registry (EBCR) between 2010 and 2014. Respondents provided data on contraception use, pregnancy history, and antiepileptic drug (AED) treatment. Patients were between ages 18 and 47 (mean, 28.5). Approximately 8.7% of the cohort were minorities, and 39.8% had household incomes of $25,000 or less.

Pregnancy history data included number of pregnancies, number of planned or unplanned pregnancies, AED type used during pregnancies, and pregnancy outcomes such as live birth, induced abortion, and SFL. Patients were categorized as receiving no therapy, monotherapy, or polytherapy. AED use was further subdivided into no AED, enzyme-inducing AED, non–enzyme-inducing AED, enzyme-inhibiting AED, glucuronidated AED, and mixed.

Most Pregnancies Were Unplanned

Of 794 pregnancies, 530 (66.8%) were unplanned and 264 (33.2%) were planned. Outcomes included 473 live births (59.6%), 141 induced abortions (17.8%), and 180 SFLs (22.7%). Among patients who did not have an induced abortion, SFL risk was higher if the pregnancy was unplanned (137 patients, 35.0%), compared with planned (43 patients, 16.4%) The risk ratio (RR) of SFL was 2.14. According to a regression analysis, SFL risk was higher for patients where “planning was entered alone” in unplanned pregnancies (odds ratio [OR], 2.75), as well as when adjusted for AED category, maternal age, and interpregnancy interval (OR, 3.57).

There was an association between maternal age (OR, 0.957) and risk of SFL. Risk was lower in the 18- to 27-year-olds (118 patients; 29.5%; RR, 0.57) and 28- to 37-year-olds (44 patients; 20.8%; RR, 0.40), compared with the under-18 group (15 patients, 51.7%). Risk of SFL was related to interpregnancy interval (OR, 2.878). This risk was greater if the interpregnancy interval was under one year (56 patients, 45.9%), compared with one year (56 patients, 22.8%) or higher (RR, 2.02).

The Epilepsy Foun-dation and Lundbeck funded the study. Dr. Herzog reports grants, and two coauthors received salary support from grants, from the two organizations.

—Jeff Craven

Suggested Reading

Herzog AG, Mandle HB, MacEachern DB. Association of unintended pregnancy with spontaneous fetal loss in women with epilepsy: findings of the Epilepsy Birth Control Registry. JAMA Neurol. 2018 Oct 15 [Epub ahead of print].

Unplanned pregnancy among women with epilepsy is associated with twice the risk of spontaneous fetal loss (SFL) when compared with women with epilepsy who planned their pregnancy, according to results from a retrospective study published online ahead of print October 15 in JAMA Neurology.

“This analysis adds the finding that unplanned pregnancy may increase the risk of SFL in women with epilepsy and identifies pregnancy planning, maternal age, and interpregnancy interval as significant modifiable variables,” said Andrew G. Herzog, MD, a neurologist at the Harvard Neuroendocrine Unit at Beth Israel Deaconess Medical Center in Wellesley, Massachusetts, and colleagues.

The Epilepsy Birth Control Registry

The researchers examined results from a web-based survey completed by 1,144 women in the Epilepsy Birth Control Registry (EBCR) between 2010 and 2014. Respondents provided data on contraception use, pregnancy history, and antiepileptic drug (AED) treatment. Patients were between ages 18 and 47 (mean, 28.5). Approximately 8.7% of the cohort were minorities, and 39.8% had household incomes of $25,000 or less.

Pregnancy history data included number of pregnancies, number of planned or unplanned pregnancies, AED type used during pregnancies, and pregnancy outcomes such as live birth, induced abortion, and SFL. Patients were categorized as receiving no therapy, monotherapy, or polytherapy. AED use was further subdivided into no AED, enzyme-inducing AED, non–enzyme-inducing AED, enzyme-inhibiting AED, glucuronidated AED, and mixed.

Most Pregnancies Were Unplanned

Of 794 pregnancies, 530 (66.8%) were unplanned and 264 (33.2%) were planned. Outcomes included 473 live births (59.6%), 141 induced abortions (17.8%), and 180 SFLs (22.7%). Among patients who did not have an induced abortion, SFL risk was higher if the pregnancy was unplanned (137 patients, 35.0%), compared with planned (43 patients, 16.4%) The risk ratio (RR) of SFL was 2.14. According to a regression analysis, SFL risk was higher for patients where “planning was entered alone” in unplanned pregnancies (odds ratio [OR], 2.75), as well as when adjusted for AED category, maternal age, and interpregnancy interval (OR, 3.57).

There was an association between maternal age (OR, 0.957) and risk of SFL. Risk was lower in the 18- to 27-year-olds (118 patients; 29.5%; RR, 0.57) and 28- to 37-year-olds (44 patients; 20.8%; RR, 0.40), compared with the under-18 group (15 patients, 51.7%). Risk of SFL was related to interpregnancy interval (OR, 2.878). This risk was greater if the interpregnancy interval was under one year (56 patients, 45.9%), compared with one year (56 patients, 22.8%) or higher (RR, 2.02).

The Epilepsy Foun-dation and Lundbeck funded the study. Dr. Herzog reports grants, and two coauthors received salary support from grants, from the two organizations.

—Jeff Craven

Suggested Reading

Herzog AG, Mandle HB, MacEachern DB. Association of unintended pregnancy with spontaneous fetal loss in women with epilepsy: findings of the Epilepsy Birth Control Registry. JAMA Neurol. 2018 Oct 15 [Epub ahead of print].

NEW ORLEANS – Adults with focal epilepsy experience a range of disturbing symptoms and functional impacts of the disease, according to a study presented at the annual meeting of the American Epilepsy Society. The most prominent symptoms and effects on daily life may differ in the early, middle, and late stages of the disease, the results suggest.

Lead study author Jacqueline A. French, MD, professor of neurology at New York University, and her colleagues interviewed 62 patients with focal-onset epilepsy to examine patients’ experiences living with epilepsy. The investigators focused on salient symptoms and functional impacts – those that were reported by at least 50% of patients and were associated with a high degree of disturbance (patients rated them 5 or greater on a scale from 0 [no disturbance] to 10 [high disturbance]).

Of 51 symptoms that patients described during the interviews, the following 8 met the salience criteria for the total cohort: twitching or tremors, confusion, difficulty in talking, loss of awareness of others’ presence, stiffening, impaired consciousness or loss of consciousness, difficulty in remembering, and dizziness or lightheadedness. Patients reported salient functional impacts on driving and transportation, work and school, and leisure and social activities. Some symptoms met salience criteria among patients in certain stages of the disease (for example, tongue biting in patients with early-stage epilepsy and anxiety, fear, or panic in late-stage epilepsy) but not among patients in the other cohorts.

“These findings underscore the need to consider all these experiences when developing patient-reported outcome measures for use in clinical trials,” said Dr. French and her colleagues. “It may be useful to tailor measures of patient experiences to the patient’s stage of disease.”

Previous qualitative studies of epilepsy symptoms and burdens were based on small numbers of patients and interviews at a single center. For the present study, the researchers conducted qualitative, semistructured, in-person interviews with adults with focal epilepsy in different areas of the United States (such as California, Minnesota, New York, Ohio, and Pennsylvania). Patients were grouped by early, middle, or late disease stage. Patients in the early cohort (n = 19) had at least two seizures in the past year, a diagnosis of focal epilepsy in the past year, and had not yet received antiepileptic drug (AED) treatment or had received treatment with only one AED and had not failed treatment. Patients in the middle cohort (n = 17) had at least one seizure in the past year, a diagnosis of focal epilepsy within the past 5 years, and had failed one AED because of lack of efficacy or had received their first add-on AED. Patients in the late cohort (n = 26) had at least one seizure every 3 months during the past year, a diagnosis of focal epilepsy at age 12 years or older, and inadequate response to treatment of at least 3 months with two AEDs that were tolerated and appropriately chosen.

Patients’ mean age was 37 years (range, 19-60 years), 73% were female, 79% were white, 69% had a college degree as their highest level of education, and 65% were employed. Patients’ seizure types included simple partial without motor signs (52%), simple partial with motor signs (16%), complex partial (68%), or secondarily generalized (65%).

While driving or transportation was a salient impact for all three groups, memory loss was a salient impact in the early and middle cohorts only. Headaches and sadness or depression were salient impacts for the late cohort only.

This study was funded by Eisai and two of the authors are former or current employees of Eisai.

[email protected]

SOURCE: French JA et al. AES 2018, Abstract 1.196.

NEW ORLEANS – Adults with focal epilepsy experience a range of disturbing symptoms and functional impacts of the disease, according to a study presented at the annual meeting of the American Epilepsy Society. The most prominent symptoms and effects on daily life may differ in the early, middle, and late stages of the disease, the results suggest.

Lead study author Jacqueline A. French, MD, professor of neurology at New York University, and her colleagues interviewed 62 patients with focal-onset epilepsy to examine patients’ experiences living with epilepsy. The investigators focused on salient symptoms and functional impacts – those that were reported by at least 50% of patients and were associated with a high degree of disturbance (patients rated them 5 or greater on a scale from 0 [no disturbance] to 10 [high disturbance]).

Of 51 symptoms that patients described during the interviews, the following 8 met the salience criteria for the total cohort: twitching or tremors, confusion, difficulty in talking, loss of awareness of others’ presence, stiffening, impaired consciousness or loss of consciousness, difficulty in remembering, and dizziness or lightheadedness. Patients reported salient functional impacts on driving and transportation, work and school, and leisure and social activities. Some symptoms met salience criteria among patients in certain stages of the disease (for example, tongue biting in patients with early-stage epilepsy and anxiety, fear, or panic in late-stage epilepsy) but not among patients in the other cohorts.

“These findings underscore the need to consider all these experiences when developing patient-reported outcome measures for use in clinical trials,” said Dr. French and her colleagues. “It may be useful to tailor measures of patient experiences to the patient’s stage of disease.”

Previous qualitative studies of epilepsy symptoms and burdens were based on small numbers of patients and interviews at a single center. For the present study, the researchers conducted qualitative, semistructured, in-person interviews with adults with focal epilepsy in different areas of the United States (such as California, Minnesota, New York, Ohio, and Pennsylvania). Patients were grouped by early, middle, or late disease stage. Patients in the early cohort (n = 19) had at least two seizures in the past year, a diagnosis of focal epilepsy in the past year, and had not yet received antiepileptic drug (AED) treatment or had received treatment with only one AED and had not failed treatment. Patients in the middle cohort (n = 17) had at least one seizure in the past year, a diagnosis of focal epilepsy within the past 5 years, and had failed one AED because of lack of efficacy or had received their first add-on AED. Patients in the late cohort (n = 26) had at least one seizure every 3 months during the past year, a diagnosis of focal epilepsy at age 12 years or older, and inadequate response to treatment of at least 3 months with two AEDs that were tolerated and appropriately chosen.

Patients’ mean age was 37 years (range, 19-60 years), 73% were female, 79% were white, 69% had a college degree as their highest level of education, and 65% were employed. Patients’ seizure types included simple partial without motor signs (52%), simple partial with motor signs (16%), complex partial (68%), or secondarily generalized (65%).

While driving or transportation was a salient impact for all three groups, memory loss was a salient impact in the early and middle cohorts only. Headaches and sadness or depression were salient impacts for the late cohort only.

This study was funded by Eisai and two of the authors are former or current employees of Eisai.

[email protected]

SOURCE: French JA et al. AES 2018, Abstract 1.196.

NEW ORLEANS – Adults with focal epilepsy experience a range of disturbing symptoms and functional impacts of the disease, according to a study presented at the annual meeting of the American Epilepsy Society. The most prominent symptoms and effects on daily life may differ in the early, middle, and late stages of the disease, the results suggest.

Lead study author Jacqueline A. French, MD, professor of neurology at New York University, and her colleagues interviewed 62 patients with focal-onset epilepsy to examine patients’ experiences living with epilepsy. The investigators focused on salient symptoms and functional impacts – those that were reported by at least 50% of patients and were associated with a high degree of disturbance (patients rated them 5 or greater on a scale from 0 [no disturbance] to 10 [high disturbance]).

Of 51 symptoms that patients described during the interviews, the following 8 met the salience criteria for the total cohort: twitching or tremors, confusion, difficulty in talking, loss of awareness of others’ presence, stiffening, impaired consciousness or loss of consciousness, difficulty in remembering, and dizziness or lightheadedness. Patients reported salient functional impacts on driving and transportation, work and school, and leisure and social activities. Some symptoms met salience criteria among patients in certain stages of the disease (for example, tongue biting in patients with early-stage epilepsy and anxiety, fear, or panic in late-stage epilepsy) but not among patients in the other cohorts.

“These findings underscore the need to consider all these experiences when developing patient-reported outcome measures for use in clinical trials,” said Dr. French and her colleagues. “It may be useful to tailor measures of patient experiences to the patient’s stage of disease.”

Previous qualitative studies of epilepsy symptoms and burdens were based on small numbers of patients and interviews at a single center. For the present study, the researchers conducted qualitative, semistructured, in-person interviews with adults with focal epilepsy in different areas of the United States (such as California, Minnesota, New York, Ohio, and Pennsylvania). Patients were grouped by early, middle, or late disease stage. Patients in the early cohort (n = 19) had at least two seizures in the past year, a diagnosis of focal epilepsy in the past year, and had not yet received antiepileptic drug (AED) treatment or had received treatment with only one AED and had not failed treatment. Patients in the middle cohort (n = 17) had at least one seizure in the past year, a diagnosis of focal epilepsy within the past 5 years, and had failed one AED because of lack of efficacy or had received their first add-on AED. Patients in the late cohort (n = 26) had at least one seizure every 3 months during the past year, a diagnosis of focal epilepsy at age 12 years or older, and inadequate response to treatment of at least 3 months with two AEDs that were tolerated and appropriately chosen.

Patients’ mean age was 37 years (range, 19-60 years), 73% were female, 79% were white, 69% had a college degree as their highest level of education, and 65% were employed. Patients’ seizure types included simple partial without motor signs (52%), simple partial with motor signs (16%), complex partial (68%), or secondarily generalized (65%).

While driving or transportation was a salient impact for all three groups, memory loss was a salient impact in the early and middle cohorts only. Headaches and sadness or depression were salient impacts for the late cohort only.

This study was funded by Eisai and two of the authors are former or current employees of Eisai.

[email protected]

SOURCE: French JA et al. AES 2018, Abstract 1.196.

NEW ORLEANS – For patients with Dravet syndrome, a 44% or greater reduction in seizure frequency can be considered a clinically meaningful response, according to a study described at the annual meeting of the American Epilepsy Society. A reduction in seizure frequency of between 60% and 68% is associated with Clinical Global Impression of Improvement (CGI-I) ratings of “very much improved,” as assessed by caregivers and investigators.

“Further analyses from other phase III studies in Dravet syndrome and other patient populations should be performed to confirm these findings and explore other potential factors that contribute to caregiver and investigator CGI-I ratings, such as nonseizure outcomes and tolerability,” said Arnold Gammaitoni, PharmD, vice president of medical and scientific affairs at Zogenix in San Diego, and his colleagues.

A 50% reduction in seizure frequency is conventionally considered to be the cutoff for a clinically meaningful change. To develop an evidence-based definition of clinically meaningful seizure reduction, Dr. Gammaitoni and colleagues examined data from a phase III, randomized, double-blind, placebo-controlled trial of fenfluramine HCl oral solution for the adjunctive treatment of seizures associated with Dravet syndrome. The investigators took an anchor-based approach and examined the percentage change in seizure frequency, along with caregiver and investigator CGI-I ratings.

A total of 119 patients with Dravet syndrome were enrolled and randomized in equal groups to placebo, 0.2 mg/kg per day of fenfluramine HCl, or 0.8 mg/kg per day of fenfluramine HCl. After a 2-week titration period, patients entered a 12-week maintenance period. Patients in the 0.8-mg/kg per day group had a 63.9% greater reduction in seizure frequency than controls did.

After the 14-week titration and maintenance period, caregivers and investigators rated the change in participants’ clinical status from baseline, using the CGI-I scale, on which responses range from 1 (very much improved) to 7 (very much worse). The investigators considered patients with CGI-I scores of 1 or 2 (much improved) to have achieved a clinically meaningful response. A score of 3 (minimally improved) was not considered meaningful. The researchers pooled the results of the three treatment groups for this analysis. They estimated the clinically meaningful percentage change in seizure frequency using receiver operating characteristic analysis of binary CGI-I score, compared with percentage change in seizure frequency, and defined it as the cut-point for which specificity and sensitivity were equal or most similar.

Caregivers and investigators provided CGI-I assessments for 112 patients and 114 patients, respectively. The receiver operating characteristic analysis identified a 44% reduction in seizure frequency as a clinically meaningful cutoff point for caregiver and investigator assessments. Using this threshold, 75%, 46%, and 12.5% of patients in the 0.8-mg/kg per day, 0.2-mg/kg per day, and placebo groups, respectively, achieved a clinically meaningful reduction from baseline in seizure frequency in the phase III study.

“The use of external anchors is one method to define a clinically meaningful change in seizure frequency,” said Dr. Gammaitoni. “Having a defined minimum clinically important difference like this allows clinicians to assess impacts of treatments on an individual patient basis.... This is a chance for others to do similar types of analyses to confirm the findings that we have had in this first study with bigger data sets, in terms of using external anchors and data to define what a clinically meaningful change is.”

Zogenix, which is developing the fenfluramine formulation examined in this study, provided funding for this research.
 

[email protected]

SOURCE: Nabbout R et al. AES 2018, Abstract 3.202.

NEW ORLEANS – For patients with Dravet syndrome, a 44% or greater reduction in seizure frequency can be considered a clinically meaningful response, according to a study described at the annual meeting of the American Epilepsy Society. A reduction in seizure frequency of between 60% and 68% is associated with Clinical Global Impression of Improvement (CGI-I) ratings of “very much improved,” as assessed by caregivers and investigators.

“Further analyses from other phase III studies in Dravet syndrome and other patient populations should be performed to confirm these findings and explore other potential factors that contribute to caregiver and investigator CGI-I ratings, such as nonseizure outcomes and tolerability,” said Arnold Gammaitoni, PharmD, vice president of medical and scientific affairs at Zogenix in San Diego, and his colleagues.

A 50% reduction in seizure frequency is conventionally considered to be the cutoff for a clinically meaningful change. To develop an evidence-based definition of clinically meaningful seizure reduction, Dr. Gammaitoni and colleagues examined data from a phase III, randomized, double-blind, placebo-controlled trial of fenfluramine HCl oral solution for the adjunctive treatment of seizures associated with Dravet syndrome. The investigators took an anchor-based approach and examined the percentage change in seizure frequency, along with caregiver and investigator CGI-I ratings.

A total of 119 patients with Dravet syndrome were enrolled and randomized in equal groups to placebo, 0.2 mg/kg per day of fenfluramine HCl, or 0.8 mg/kg per day of fenfluramine HCl. After a 2-week titration period, patients entered a 12-week maintenance period. Patients in the 0.8-mg/kg per day group had a 63.9% greater reduction in seizure frequency than controls did.

After the 14-week titration and maintenance period, caregivers and investigators rated the change in participants’ clinical status from baseline, using the CGI-I scale, on which responses range from 1 (very much improved) to 7 (very much worse). The investigators considered patients with CGI-I scores of 1 or 2 (much improved) to have achieved a clinically meaningful response. A score of 3 (minimally improved) was not considered meaningful. The researchers pooled the results of the three treatment groups for this analysis. They estimated the clinically meaningful percentage change in seizure frequency using receiver operating characteristic analysis of binary CGI-I score, compared with percentage change in seizure frequency, and defined it as the cut-point for which specificity and sensitivity were equal or most similar.

Caregivers and investigators provided CGI-I assessments for 112 patients and 114 patients, respectively. The receiver operating characteristic analysis identified a 44% reduction in seizure frequency as a clinically meaningful cutoff point for caregiver and investigator assessments. Using this threshold, 75%, 46%, and 12.5% of patients in the 0.8-mg/kg per day, 0.2-mg/kg per day, and placebo groups, respectively, achieved a clinically meaningful reduction from baseline in seizure frequency in the phase III study.

“The use of external anchors is one method to define a clinically meaningful change in seizure frequency,” said Dr. Gammaitoni. “Having a defined minimum clinically important difference like this allows clinicians to assess impacts of treatments on an individual patient basis.... This is a chance for others to do similar types of analyses to confirm the findings that we have had in this first study with bigger data sets, in terms of using external anchors and data to define what a clinically meaningful change is.”

Zogenix, which is developing the fenfluramine formulation examined in this study, provided funding for this research.
 

[email protected]

SOURCE: Nabbout R et al. AES 2018, Abstract 3.202.

NEW ORLEANS – For patients with Dravet syndrome, a 44% or greater reduction in seizure frequency can be considered a clinically meaningful response, according to a study described at the annual meeting of the American Epilepsy Society. A reduction in seizure frequency of between 60% and 68% is associated with Clinical Global Impression of Improvement (CGI-I) ratings of “very much improved,” as assessed by caregivers and investigators.

“Further analyses from other phase III studies in Dravet syndrome and other patient populations should be performed to confirm these findings and explore other potential factors that contribute to caregiver and investigator CGI-I ratings, such as nonseizure outcomes and tolerability,” said Arnold Gammaitoni, PharmD, vice president of medical and scientific affairs at Zogenix in San Diego, and his colleagues.

A 50% reduction in seizure frequency is conventionally considered to be the cutoff for a clinically meaningful change. To develop an evidence-based definition of clinically meaningful seizure reduction, Dr. Gammaitoni and colleagues examined data from a phase III, randomized, double-blind, placebo-controlled trial of fenfluramine HCl oral solution for the adjunctive treatment of seizures associated with Dravet syndrome. The investigators took an anchor-based approach and examined the percentage change in seizure frequency, along with caregiver and investigator CGI-I ratings.

A total of 119 patients with Dravet syndrome were enrolled and randomized in equal groups to placebo, 0.2 mg/kg per day of fenfluramine HCl, or 0.8 mg/kg per day of fenfluramine HCl. After a 2-week titration period, patients entered a 12-week maintenance period. Patients in the 0.8-mg/kg per day group had a 63.9% greater reduction in seizure frequency than controls did.

After the 14-week titration and maintenance period, caregivers and investigators rated the change in participants’ clinical status from baseline, using the CGI-I scale, on which responses range from 1 (very much improved) to 7 (very much worse). The investigators considered patients with CGI-I scores of 1 or 2 (much improved) to have achieved a clinically meaningful response. A score of 3 (minimally improved) was not considered meaningful. The researchers pooled the results of the three treatment groups for this analysis. They estimated the clinically meaningful percentage change in seizure frequency using receiver operating characteristic analysis of binary CGI-I score, compared with percentage change in seizure frequency, and defined it as the cut-point for which specificity and sensitivity were equal or most similar.

Caregivers and investigators provided CGI-I assessments for 112 patients and 114 patients, respectively. The receiver operating characteristic analysis identified a 44% reduction in seizure frequency as a clinically meaningful cutoff point for caregiver and investigator assessments. Using this threshold, 75%, 46%, and 12.5% of patients in the 0.8-mg/kg per day, 0.2-mg/kg per day, and placebo groups, respectively, achieved a clinically meaningful reduction from baseline in seizure frequency in the phase III study.

“The use of external anchors is one method to define a clinically meaningful change in seizure frequency,” said Dr. Gammaitoni. “Having a defined minimum clinically important difference like this allows clinicians to assess impacts of treatments on an individual patient basis.... This is a chance for others to do similar types of analyses to confirm the findings that we have had in this first study with bigger data sets, in terms of using external anchors and data to define what a clinically meaningful change is.”

Zogenix, which is developing the fenfluramine formulation examined in this study, provided funding for this research.
 

[email protected]

SOURCE: Nabbout R et al. AES 2018, Abstract 3.202.

A community-based program that helps patients with epilepsy self-manage their condition and related psychiatric problems has proven effective in reducing the severity of depression according to a study published in Epilepsy and Behavior.

• Community Targeted Self-Management for Epilepsy and Mental Illness (C-TIME), a behavioral program, consisted of ten 60 to 90-minute sessions conducted over 12 weeks.
• The program included outreach and engagement efforts to help patients suffering from both epilepsy and mental health conditions.
• Thirty patients were enrolled in the program; four months after participating in C-TIME, 66% of the enrolled patients were available for outcome evaluation.
• Researchers reported significant reduction in depression severity, and more than 90% of the group said they were satisfied with results.

Sajatovic M, Needham K, Colón-Zimmermann K, et al. The Community-targeted Self-management of Epilepsy and Mental Illness (C-TIME) initiative: A research, community, and healthcare administration partnership to reduce epilepsy burden [published online ahead of print October 29, 2018]. Epilepsy Behav.  https://doi.org/10.1016/j.yebeh.2018.10.004

A community-based program that helps patients with epilepsy self-manage their condition and related psychiatric problems has proven effective in reducing the severity of depression according to a study published in Epilepsy and Behavior.

• Community Targeted Self-Management for Epilepsy and Mental Illness (C-TIME), a behavioral program, consisted of ten 60 to 90-minute sessions conducted over 12 weeks.
• The program included outreach and engagement efforts to help patients suffering from both epilepsy and mental health conditions.
• Thirty patients were enrolled in the program; four months after participating in C-TIME, 66% of the enrolled patients were available for outcome evaluation.
• Researchers reported significant reduction in depression severity, and more than 90% of the group said they were satisfied with results.

Sajatovic M, Needham K, Colón-Zimmermann K, et al. The Community-targeted Self-management of Epilepsy and Mental Illness (C-TIME) initiative: A research, community, and healthcare administration partnership to reduce epilepsy burden [published online ahead of print October 29, 2018]. Epilepsy Behav.  https://doi.org/10.1016/j.yebeh.2018.10.004

A community-based program that helps patients with epilepsy self-manage their condition and related psychiatric problems has proven effective in reducing the severity of depression according to a study published in Epilepsy and Behavior.

• Community Targeted Self-Management for Epilepsy and Mental Illness (C-TIME), a behavioral program, consisted of ten 60 to 90-minute sessions conducted over 12 weeks.
• The program included outreach and engagement efforts to help patients suffering from both epilepsy and mental health conditions.
• Thirty patients were enrolled in the program; four months after participating in C-TIME, 66% of the enrolled patients were available for outcome evaluation.
• Researchers reported significant reduction in depression severity, and more than 90% of the group said they were satisfied with results.

Sajatovic M, Needham K, Colón-Zimmermann K, et al. The Community-targeted Self-management of Epilepsy and Mental Illness (C-TIME) initiative: A research, community, and healthcare administration partnership to reduce epilepsy burden [published online ahead of print October 29, 2018]. Epilepsy Behav.  https://doi.org/10.1016/j.yebeh.2018.10.004

The Epilepsy Foundation, working with a pharmaceutical company, has launched an educational initiative to locate communities most in need of professional and consumer education. The program emphasizes the value of tailored and innovative approaches to reach underserved populations to improve their self-management skills for epilepsy.

• A data analysis conducted by The Connectors Project found 4 states in need of help: Michigan, Oklahoma, Nevada, and West Virginia, all of which have rural and/or underserved communities.
• The Foundation launched outreach and awareness programs in these states, as well as digital and in-person education for clinicians, patients, and families.
• The initiatives were designed to fill critical gaps in patients’ ability to self-manage epilepsy and gaps in their ability to get access to quality professional care.

Owens S, Sirven JI, Shafer PO, et al. Innovative approaches reaching underserved and rural communities to improve epilepsy care: A review of the methodology of the Connectors Project [published online ahead of print October 31, 2018]. Epilepsy Behav. https://doi.org/10.1016/j.yebeh.2018.09.029

The Epilepsy Foundation, working with a pharmaceutical company, has launched an educational initiative to locate communities most in need of professional and consumer education. The program emphasizes the value of tailored and innovative approaches to reach underserved populations to improve their self-management skills for epilepsy.

• A data analysis conducted by The Connectors Project found 4 states in need of help: Michigan, Oklahoma, Nevada, and West Virginia, all of which have rural and/or underserved communities.
• The Foundation launched outreach and awareness programs in these states, as well as digital and in-person education for clinicians, patients, and families.
• The initiatives were designed to fill critical gaps in patients’ ability to self-manage epilepsy and gaps in their ability to get access to quality professional care.

Owens S, Sirven JI, Shafer PO, et al. Innovative approaches reaching underserved and rural communities to improve epilepsy care: A review of the methodology of the Connectors Project [published online ahead of print October 31, 2018]. Epilepsy Behav. https://doi.org/10.1016/j.yebeh.2018.09.029

The Epilepsy Foundation, working with a pharmaceutical company, has launched an educational initiative to locate communities most in need of professional and consumer education. The program emphasizes the value of tailored and innovative approaches to reach underserved populations to improve their self-management skills for epilepsy.

• A data analysis conducted by The Connectors Project found 4 states in need of help: Michigan, Oklahoma, Nevada, and West Virginia, all of which have rural and/or underserved communities.
• The Foundation launched outreach and awareness programs in these states, as well as digital and in-person education for clinicians, patients, and families.
• The initiatives were designed to fill critical gaps in patients’ ability to self-manage epilepsy and gaps in their ability to get access to quality professional care.

Owens S, Sirven JI, Shafer PO, et al. Innovative approaches reaching underserved and rural communities to improve epilepsy care: A review of the methodology of the Connectors Project [published online ahead of print October 31, 2018]. Epilepsy Behav. https://doi.org/10.1016/j.yebeh.2018.09.029

Giving neurologists the tools to diagnose and treat common psychiatric disorders can help meet the mental health needs of adults with epilepsy whose psychiatric comorbidities are being ignored, according to investigators from Wake Forest School of Medicine and Johns Hopkins University.

• There is a high prevalence of psychiatric disorders among adults with epilepsy.
• These comorbidities are often overlooked because patients have limited access to mental health services.
• Heidi Munger Clary and Jay Salpekar suggest that letting neurologists diagnose and manage common conditions like mood and anxiety disorders will help address this dilemma.
• The researchers suggest that validated screeners could help neurologists who do not have expertise in psychiatry to manage depression and anxiety.
• With such assistance, adult neurologists could be trained to effectively use selective serotonin reupdate inhibitors (SSRIs).

Munger Clary HM, Salpekar JA. Should adult neurologists play a role in the management of the most common psychiatric comorbidities? Practical considerations [published online ahead of print November 22, 2018]. Epilepsy Behav. https://doi.org/10.1016/j.yebeh.2018.10.020

Giving neurologists the tools to diagnose and treat common psychiatric disorders can help meet the mental health needs of adults with epilepsy whose psychiatric comorbidities are being ignored, according to investigators from Wake Forest School of Medicine and Johns Hopkins University.

• There is a high prevalence of psychiatric disorders among adults with epilepsy.
• These comorbidities are often overlooked because patients have limited access to mental health services.
• Heidi Munger Clary and Jay Salpekar suggest that letting neurologists diagnose and manage common conditions like mood and anxiety disorders will help address this dilemma.
• The researchers suggest that validated screeners could help neurologists who do not have expertise in psychiatry to manage depression and anxiety.
• With such assistance, adult neurologists could be trained to effectively use selective serotonin reupdate inhibitors (SSRIs).

Munger Clary HM, Salpekar JA. Should adult neurologists play a role in the management of the most common psychiatric comorbidities? Practical considerations [published online ahead of print November 22, 2018]. Epilepsy Behav. https://doi.org/10.1016/j.yebeh.2018.10.020

Giving neurologists the tools to diagnose and treat common psychiatric disorders can help meet the mental health needs of adults with epilepsy whose psychiatric comorbidities are being ignored, according to investigators from Wake Forest School of Medicine and Johns Hopkins University.

• There is a high prevalence of psychiatric disorders among adults with epilepsy.
• These comorbidities are often overlooked because patients have limited access to mental health services.
• Heidi Munger Clary and Jay Salpekar suggest that letting neurologists diagnose and manage common conditions like mood and anxiety disorders will help address this dilemma.
• The researchers suggest that validated screeners could help neurologists who do not have expertise in psychiatry to manage depression and anxiety.
• With such assistance, adult neurologists could be trained to effectively use selective serotonin reupdate inhibitors (SSRIs).

Munger Clary HM, Salpekar JA. Should adult neurologists play a role in the management of the most common psychiatric comorbidities? Practical considerations [published online ahead of print November 22, 2018]. Epilepsy Behav. https://doi.org/10.1016/j.yebeh.2018.10.020

NEW ORLEANS – The newer antiepileptic drugs (AEDs) and the established AEDs have similar tolerability, according to an analysis presented at the annual meeting of the American Epilepsy Society. Approximately one-third of patients with epilepsy discontinue their AEDs because of adverse drug reactions, according to the researchers. An increasing number of concomitant AEDs is associated with decreasing tolerability.

Previous research by Patrick Kwan, MBBChir, PhD, chair of neurology at the University of Melbourne and his colleagues indicated that the introduction of AEDs with new mechanisms of action in the past two decades has not changed seizure outcome overall in newly diagnosed epilepsy. Researchers had not studied the long-term tolerability of AEDs, however.

Dr. Kwan, Zhibin Chen, PhD, a biostatistician at the University of Melbourne, and their colleagues examined AED-induced adverse drug reactions over a 30-year period. They analyzed data for adults who were newly treated with AEDs at the epilepsy unit of the Western Infirmary in Glasgow during July 1, 1982–Oct. 31, 2012. All patients were followed prospectively until April 30, 2016, or death. The researchers systematically reviewed patient-reported adverse drug reactions and categorized them with the Medical Dictionary for Regulatory Activities. They defined adverse reactions that resulted in AED discontinuation as intolerable.

The investigators included 1,527 patients in their analysis. Approximately 56% of the sample was male, and the median age was 37 years. Participants tried a total of 2,766 AED regimens, including 2,028 (73%) as monotherapy and 738 (27%) as combination therapy. Among the monotherapies, 927 (46%) were established AEDs, and 1,101 (54%) were newer AEDs.

In all, 675 (44%) patients reported adverse drug reactions. These reports included 391 (26%) patients with nervous system disorders (e.g., tremor, sedation, and headaches), 272 (18%) with general disorders (e.g., fatigue, ataxia, and irritability), and 136 (9%) with psychiatric disorders (e.g., aggression, depression, and mood swings). A total of 498 (33%) patients had at least one intolerable adverse drug reaction.

The established and newer AEDs, when taken as monotherapy, had similar rates of intolerable adverse drug reactions (odds ratio, 1.09).The crude rate of intolerable adverse drug reactions appeared to increase for each additional AED regimen tried. Multivariable analysis indicated that women were more likely to report intolerable adverse drug reactions than men.

Compared with patients taking monotherapy, patients taking two AEDs had 1.67 times the risk of developing an intolerable adverse drug reaction, after data adjustments for number of previous AED regimens tried, previous intolerable adverse drug reaction, age, sex, pretreatment psychiatric comorbidity, and epilepsy type. The odds increased further in patients on three AEDs (OR, 2.38) and four AEDs (OR, 5.24). Patients who had intolerable adverse drug reactions to previous AED regimens had much greater odds of experiencing a further event (OR, 22.7).

After considering all the above factors, the researchers found that the odds of intolerable adverse drug reactions decreased for each additional AED regimen. When analyzing the 642 patients who took more than one AED regimen, they found that those who failed the first AED because of adverse drug reactions were more likely to develop intolerable adverse drug reactions to subsequent regimens (OR, 5.09). The odds of drug withdrawal because of adverse drug reaction increased 12-fold for each additional previous intolerable adverse drug reaction (OR, 13.3).

The investigators received no funding for this study.
 

This article was updated 12/4/18.

[email protected]

SOURCE: Alsfouk B et al. AES 2018, Abstract 2.275.

NEW ORLEANS – The newer antiepileptic drugs (AEDs) and the established AEDs have similar tolerability, according to an analysis presented at the annual meeting of the American Epilepsy Society. Approximately one-third of patients with epilepsy discontinue their AEDs because of adverse drug reactions, according to the researchers. An increasing number of concomitant AEDs is associated with decreasing tolerability.

Previous research by Patrick Kwan, MBBChir, PhD, chair of neurology at the University of Melbourne and his colleagues indicated that the introduction of AEDs with new mechanisms of action in the past two decades has not changed seizure outcome overall in newly diagnosed epilepsy. Researchers had not studied the long-term tolerability of AEDs, however.

Dr. Kwan, Zhibin Chen, PhD, a biostatistician at the University of Melbourne, and their colleagues examined AED-induced adverse drug reactions over a 30-year period. They analyzed data for adults who were newly treated with AEDs at the epilepsy unit of the Western Infirmary in Glasgow during July 1, 1982–Oct. 31, 2012. All patients were followed prospectively until April 30, 2016, or death. The researchers systematically reviewed patient-reported adverse drug reactions and categorized them with the Medical Dictionary for Regulatory Activities. They defined adverse reactions that resulted in AED discontinuation as intolerable.

The investigators included 1,527 patients in their analysis. Approximately 56% of the sample was male, and the median age was 37 years. Participants tried a total of 2,766 AED regimens, including 2,028 (73%) as monotherapy and 738 (27%) as combination therapy. Among the monotherapies, 927 (46%) were established AEDs, and 1,101 (54%) were newer AEDs.

In all, 675 (44%) patients reported adverse drug reactions. These reports included 391 (26%) patients with nervous system disorders (e.g., tremor, sedation, and headaches), 272 (18%) with general disorders (e.g., fatigue, ataxia, and irritability), and 136 (9%) with psychiatric disorders (e.g., aggression, depression, and mood swings). A total of 498 (33%) patients had at least one intolerable adverse drug reaction.

The established and newer AEDs, when taken as monotherapy, had similar rates of intolerable adverse drug reactions (odds ratio, 1.09).The crude rate of intolerable adverse drug reactions appeared to increase for each additional AED regimen tried. Multivariable analysis indicated that women were more likely to report intolerable adverse drug reactions than men.

Compared with patients taking monotherapy, patients taking two AEDs had 1.67 times the risk of developing an intolerable adverse drug reaction, after data adjustments for number of previous AED regimens tried, previous intolerable adverse drug reaction, age, sex, pretreatment psychiatric comorbidity, and epilepsy type. The odds increased further in patients on three AEDs (OR, 2.38) and four AEDs (OR, 5.24). Patients who had intolerable adverse drug reactions to previous AED regimens had much greater odds of experiencing a further event (OR, 22.7).

After considering all the above factors, the researchers found that the odds of intolerable adverse drug reactions decreased for each additional AED regimen. When analyzing the 642 patients who took more than one AED regimen, they found that those who failed the first AED because of adverse drug reactions were more likely to develop intolerable adverse drug reactions to subsequent regimens (OR, 5.09). The odds of drug withdrawal because of adverse drug reaction increased 12-fold for each additional previous intolerable adverse drug reaction (OR, 13.3).

The investigators received no funding for this study.
 

This article was updated 12/4/18.

[email protected]

SOURCE: Alsfouk B et al. AES 2018, Abstract 2.275.

NEW ORLEANS – The newer antiepileptic drugs (AEDs) and the established AEDs have similar tolerability, according to an analysis presented at the annual meeting of the American Epilepsy Society. Approximately one-third of patients with epilepsy discontinue their AEDs because of adverse drug reactions, according to the researchers. An increasing number of concomitant AEDs is associated with decreasing tolerability.

Previous research by Patrick Kwan, MBBChir, PhD, chair of neurology at the University of Melbourne and his colleagues indicated that the introduction of AEDs with new mechanisms of action in the past two decades has not changed seizure outcome overall in newly diagnosed epilepsy. Researchers had not studied the long-term tolerability of AEDs, however.

Dr. Kwan, Zhibin Chen, PhD, a biostatistician at the University of Melbourne, and their colleagues examined AED-induced adverse drug reactions over a 30-year period. They analyzed data for adults who were newly treated with AEDs at the epilepsy unit of the Western Infirmary in Glasgow during July 1, 1982–Oct. 31, 2012. All patients were followed prospectively until April 30, 2016, or death. The researchers systematically reviewed patient-reported adverse drug reactions and categorized them with the Medical Dictionary for Regulatory Activities. They defined adverse reactions that resulted in AED discontinuation as intolerable.

The investigators included 1,527 patients in their analysis. Approximately 56% of the sample was male, and the median age was 37 years. Participants tried a total of 2,766 AED regimens, including 2,028 (73%) as monotherapy and 738 (27%) as combination therapy. Among the monotherapies, 927 (46%) were established AEDs, and 1,101 (54%) were newer AEDs.

In all, 675 (44%) patients reported adverse drug reactions. These reports included 391 (26%) patients with nervous system disorders (e.g., tremor, sedation, and headaches), 272 (18%) with general disorders (e.g., fatigue, ataxia, and irritability), and 136 (9%) with psychiatric disorders (e.g., aggression, depression, and mood swings). A total of 498 (33%) patients had at least one intolerable adverse drug reaction.

The established and newer AEDs, when taken as monotherapy, had similar rates of intolerable adverse drug reactions (odds ratio, 1.09).The crude rate of intolerable adverse drug reactions appeared to increase for each additional AED regimen tried. Multivariable analysis indicated that women were more likely to report intolerable adverse drug reactions than men.

Compared with patients taking monotherapy, patients taking two AEDs had 1.67 times the risk of developing an intolerable adverse drug reaction, after data adjustments for number of previous AED regimens tried, previous intolerable adverse drug reaction, age, sex, pretreatment psychiatric comorbidity, and epilepsy type. The odds increased further in patients on three AEDs (OR, 2.38) and four AEDs (OR, 5.24). Patients who had intolerable adverse drug reactions to previous AED regimens had much greater odds of experiencing a further event (OR, 22.7).

After considering all the above factors, the researchers found that the odds of intolerable adverse drug reactions decreased for each additional AED regimen. When analyzing the 642 patients who took more than one AED regimen, they found that those who failed the first AED because of adverse drug reactions were more likely to develop intolerable adverse drug reactions to subsequent regimens (OR, 5.09). The odds of drug withdrawal because of adverse drug reaction increased 12-fold for each additional previous intolerable adverse drug reaction (OR, 13.3).

The investigators received no funding for this study.
 

This article was updated 12/4/18.

[email protected]

SOURCE: Alsfouk B et al. AES 2018, Abstract 2.275.

NEW ORLEANS – Women with epilepsy may have greater rates of infertility and impaired fecundity, compared with the general population, based on a retrospective study presented at the annual meeting of the American Epilepsy Society.

Data recorded in the 2010-2014 Epilepsy Birth Control Registry indicates a 9.2% infertility rate and a 22.5% impaired fecundity rate among American women with epilepsy. Both rates are higher than the general population infertility rate of 6.0% and the 12.1% rate of impaired fecundity cited by the Centers for Disease Control and Prevention.

However, differences between the study of women with epilepsy and the study of the general population may limit the validity of this comparison, said Devon B. MacEachern, clinical and research coordinator at Neuroendocrine Associates in Wellesley Hills, Mass.

It is likewise uncertain whether use of antiepileptic drugs (AEDs) affects women’s fertility or fecundity.

The Epilepsy Birth Control Registry collected data from an Internet-based survey of 1,144 community-dwelling women with epilepsy aged 18-47 years. Participants provided information about demographics, epilepsy, AEDs, reproduction, and contraception.

The researchers focused on rates of infertility, impaired fecundity, and live birth or unaborted pregnancy among 978 American women, and additionally examined whether these outcomes were related to AED use.

Infertility was defined as the percentage of participants who had unprotected sex but did not become pregnant by 1 year. Impaired fecundity was the percentage of participants who were infertile or did not carry a pregnancy to live birth. The study excluded from the impaired fecundity analysis the 41 respondents whose only outcomes were induced abortions. The 18% of pregnancies that terminated as induced abortions were excluded from the live birth rate analysis.

In all, 373 registry participants had 724 pregnancies and 422 births between 1981 and 2013. The women had an average of 2.15 pregnancies at a mean age of 24.9 years (range, 13-44 years). In addition, 38 women (9.2%) tried to conceive, but were infertile. Of 306 women with a first pregnancy, 222 (72.5%) had a live birth. Among 292 women with two pregnancies, 260 (89.0%) had at least one live birth, and 180 (61.6%) had two live births.

Of the 373 women, 84 (22.5%) with pregnancies had impaired fecundity. The risk of impaired fecundity tended to be higher among women on AED polytherapy than among women on no AED (risk ratio, 1.74).

The ratio of live births to pregnancy (71.0%) was similar among women on no AEDs (71.3%), those on AED monotherapy (71.8%), and those on polytherapy (69.7%). The live birth rate was 67.5% for women taking enzyme-inducing AEDs, 89.1% for women taking glucuronidated AEDs, 72.8% for women taking nonenzyme-inducing AEDs, 63.3% for women taking enzyme-inhibiting AEDs, and 69.7% for women on polytherapy. Lamotrigine use was associated with the highest ratio of live births to pregnancies at 89.1%; valproate use was associated with the lowest ratio of live births to pregnancies at 63.3%.

The investigation was funded by the Epilepsy Foundation and Lundbeck.

[email protected]

SOURCE: MacEachern DB et al. AES 2018, Abstract 1.426.

NEW ORLEANS – Women with epilepsy may have greater rates of infertility and impaired fecundity, compared with the general population, based on a retrospective study presented at the annual meeting of the American Epilepsy Society.

Data recorded in the 2010-2014 Epilepsy Birth Control Registry indicates a 9.2% infertility rate and a 22.5% impaired fecundity rate among American women with epilepsy. Both rates are higher than the general population infertility rate of 6.0% and the 12.1% rate of impaired fecundity cited by the Centers for Disease Control and Prevention.

However, differences between the study of women with epilepsy and the study of the general population may limit the validity of this comparison, said Devon B. MacEachern, clinical and research coordinator at Neuroendocrine Associates in Wellesley Hills, Mass.

It is likewise uncertain whether use of antiepileptic drugs (AEDs) affects women’s fertility or fecundity.

The Epilepsy Birth Control Registry collected data from an Internet-based survey of 1,144 community-dwelling women with epilepsy aged 18-47 years. Participants provided information about demographics, epilepsy, AEDs, reproduction, and contraception.

The researchers focused on rates of infertility, impaired fecundity, and live birth or unaborted pregnancy among 978 American women, and additionally examined whether these outcomes were related to AED use.

Infertility was defined as the percentage of participants who had unprotected sex but did not become pregnant by 1 year. Impaired fecundity was the percentage of participants who were infertile or did not carry a pregnancy to live birth. The study excluded from the impaired fecundity analysis the 41 respondents whose only outcomes were induced abortions. The 18% of pregnancies that terminated as induced abortions were excluded from the live birth rate analysis.

In all, 373 registry participants had 724 pregnancies and 422 births between 1981 and 2013. The women had an average of 2.15 pregnancies at a mean age of 24.9 years (range, 13-44 years). In addition, 38 women (9.2%) tried to conceive, but were infertile. Of 306 women with a first pregnancy, 222 (72.5%) had a live birth. Among 292 women with two pregnancies, 260 (89.0%) had at least one live birth, and 180 (61.6%) had two live births.

Of the 373 women, 84 (22.5%) with pregnancies had impaired fecundity. The risk of impaired fecundity tended to be higher among women on AED polytherapy than among women on no AED (risk ratio, 1.74).

The ratio of live births to pregnancy (71.0%) was similar among women on no AEDs (71.3%), those on AED monotherapy (71.8%), and those on polytherapy (69.7%). The live birth rate was 67.5% for women taking enzyme-inducing AEDs, 89.1% for women taking glucuronidated AEDs, 72.8% for women taking nonenzyme-inducing AEDs, 63.3% for women taking enzyme-inhibiting AEDs, and 69.7% for women on polytherapy. Lamotrigine use was associated with the highest ratio of live births to pregnancies at 89.1%; valproate use was associated with the lowest ratio of live births to pregnancies at 63.3%.

The investigation was funded by the Epilepsy Foundation and Lundbeck.

[email protected]

SOURCE: MacEachern DB et al. AES 2018, Abstract 1.426.

NEW ORLEANS – Women with epilepsy may have greater rates of infertility and impaired fecundity, compared with the general population, based on a retrospective study presented at the annual meeting of the American Epilepsy Society.

Data recorded in the 2010-2014 Epilepsy Birth Control Registry indicates a 9.2% infertility rate and a 22.5% impaired fecundity rate among American women with epilepsy. Both rates are higher than the general population infertility rate of 6.0% and the 12.1% rate of impaired fecundity cited by the Centers for Disease Control and Prevention.

However, differences between the study of women with epilepsy and the study of the general population may limit the validity of this comparison, said Devon B. MacEachern, clinical and research coordinator at Neuroendocrine Associates in Wellesley Hills, Mass.

It is likewise uncertain whether use of antiepileptic drugs (AEDs) affects women’s fertility or fecundity.

The Epilepsy Birth Control Registry collected data from an Internet-based survey of 1,144 community-dwelling women with epilepsy aged 18-47 years. Participants provided information about demographics, epilepsy, AEDs, reproduction, and contraception.

The researchers focused on rates of infertility, impaired fecundity, and live birth or unaborted pregnancy among 978 American women, and additionally examined whether these outcomes were related to AED use.

Infertility was defined as the percentage of participants who had unprotected sex but did not become pregnant by 1 year. Impaired fecundity was the percentage of participants who were infertile or did not carry a pregnancy to live birth. The study excluded from the impaired fecundity analysis the 41 respondents whose only outcomes were induced abortions. The 18% of pregnancies that terminated as induced abortions were excluded from the live birth rate analysis.

In all, 373 registry participants had 724 pregnancies and 422 births between 1981 and 2013. The women had an average of 2.15 pregnancies at a mean age of 24.9 years (range, 13-44 years). In addition, 38 women (9.2%) tried to conceive, but were infertile. Of 306 women with a first pregnancy, 222 (72.5%) had a live birth. Among 292 women with two pregnancies, 260 (89.0%) had at least one live birth, and 180 (61.6%) had two live births.

Of the 373 women, 84 (22.5%) with pregnancies had impaired fecundity. The risk of impaired fecundity tended to be higher among women on AED polytherapy than among women on no AED (risk ratio, 1.74).

The ratio of live births to pregnancy (71.0%) was similar among women on no AEDs (71.3%), those on AED monotherapy (71.8%), and those on polytherapy (69.7%). The live birth rate was 67.5% for women taking enzyme-inducing AEDs, 89.1% for women taking glucuronidated AEDs, 72.8% for women taking nonenzyme-inducing AEDs, 63.3% for women taking enzyme-inhibiting AEDs, and 69.7% for women on polytherapy. Lamotrigine use was associated with the highest ratio of live births to pregnancies at 89.1%; valproate use was associated with the lowest ratio of live births to pregnancies at 63.3%.

The investigation was funded by the Epilepsy Foundation and Lundbeck.

[email protected]

SOURCE: MacEachern DB et al. AES 2018, Abstract 1.426.

NEW ORLEANS – Among patients with psychogenic nonepileptic seizures, the risk of death is more than twice as great as among the general population, according to data presented at the annual meeting of the American Epilepsy Society. Patients with PNES have a mortality rate comparable to that of patients with drug-resistant epilepsy.

“This [finding] emphasizes the importance of correct diagnosis and identification of relevant pathologies in order to avoid preventable deaths in an important group of patients, where medical attention is often inappropriately directed to a dramatic but ultimately irrelevant clinical feature of the condition,” said Russell Nightscales, a first-year medical student at the University of Melbourne.*

Although PNES sometimes is mistaken for epilepsy and treated accordingly, it is a form of conversion disorder. The elevated risk of death among patients with epilepsy is understood, but few researchers have studied mortality in patients with PNES.

Mr. Nightscales and his colleagues conducted a retrospective cohort study of patients who had been admitted for a comprehensive epilepsy evaluation to one of two tertiary hospital video EEG monitoring (VEM) units in Melbourne between Jan. 1, 1995, and Dec. 31, 2015. The investigators ascertained mortality and cause of death by linking patient data to the Australian National Death Index (NDI). When a coroner’s report was available, they refined the cause of death using information from the National Coronial Information System. Each patient’s diagnosis was based on the consensus opinion of experienced epileptologists at the Comprehensive Epilepsy Meeting following a review of the clinical history, VEM data, and investigations. The researchers compared mortality in patients with PNES, epilepsy, or both conditions. They extracted clinical data through medical record review. Finally, they determined lifetime history of psychiatric disorders through review of neuropsychiatric reports.

Of 3,152 patients who underwent VEM, the investigators included 2,076 patients in their analyses. Of this population, 631 patients had PNES, 1,339 had epilepsy, and 106 had both. The standardized mortality ratio (SMR) among patients with PNES was 2.6 times greater than among the general population. Patients with PNES between ages 30 and 39 had a ninefold higher risk of death, compared with the general population. The SMR of patients with epilepsy was 3.2. The investigators found no significant difference in the rate of mortality between any of the patient groups after excluding 17 patients with epilepsy and a known brain tumor at the time of VEM, who had a malignant neoplasm of the brain listed as their primary cause of death.

Death resulted from external causes in 20% of all deaths among patients with PNES and in 53% of deaths with a known cause among patients who died below the age of 50. Suicide accounted for 24% of deaths among patients with PNES in this age group. Neoplasia and cardiorespiratory causes were responsible for 51% of deaths with a known cause across all ages and 67% of those between ages 50 and 69. Among people with epilepsy, external causes accounted for 7% of all deaths. Neoplasia and cardiorespiratory causes were observed in 42% of people with epilepsy. Epilepsy was responsible for 28% of deaths with a known cause among patients with epilepsy

The research was funded by Australia’s National Health and Medical Research Council and the RMH Neuroscience Foundation.

[email protected]

SOURCE: O’Brien TJ et al. AES 2018, Abstract 1.139.

*Correction 12/4/18: An earlier version of this article misstated the name of the presenter. Russell Nightscales presented this study.

NEW ORLEANS – Among patients with psychogenic nonepileptic seizures, the risk of death is more than twice as great as among the general population, according to data presented at the annual meeting of the American Epilepsy Society. Patients with PNES have a mortality rate comparable to that of patients with drug-resistant epilepsy.

“This [finding] emphasizes the importance of correct diagnosis and identification of relevant pathologies in order to avoid preventable deaths in an important group of patients, where medical attention is often inappropriately directed to a dramatic but ultimately irrelevant clinical feature of the condition,” said Russell Nightscales, a first-year medical student at the University of Melbourne.*

Although PNES sometimes is mistaken for epilepsy and treated accordingly, it is a form of conversion disorder. The elevated risk of death among patients with epilepsy is understood, but few researchers have studied mortality in patients with PNES.

Mr. Nightscales and his colleagues conducted a retrospective cohort study of patients who had been admitted for a comprehensive epilepsy evaluation to one of two tertiary hospital video EEG monitoring (VEM) units in Melbourne between Jan. 1, 1995, and Dec. 31, 2015. The investigators ascertained mortality and cause of death by linking patient data to the Australian National Death Index (NDI). When a coroner’s report was available, they refined the cause of death using information from the National Coronial Information System. Each patient’s diagnosis was based on the consensus opinion of experienced epileptologists at the Comprehensive Epilepsy Meeting following a review of the clinical history, VEM data, and investigations. The researchers compared mortality in patients with PNES, epilepsy, or both conditions. They extracted clinical data through medical record review. Finally, they determined lifetime history of psychiatric disorders through review of neuropsychiatric reports.

Of 3,152 patients who underwent VEM, the investigators included 2,076 patients in their analyses. Of this population, 631 patients had PNES, 1,339 had epilepsy, and 106 had both. The standardized mortality ratio (SMR) among patients with PNES was 2.6 times greater than among the general population. Patients with PNES between ages 30 and 39 had a ninefold higher risk of death, compared with the general population. The SMR of patients with epilepsy was 3.2. The investigators found no significant difference in the rate of mortality between any of the patient groups after excluding 17 patients with epilepsy and a known brain tumor at the time of VEM, who had a malignant neoplasm of the brain listed as their primary cause of death.

Death resulted from external causes in 20% of all deaths among patients with PNES and in 53% of deaths with a known cause among patients who died below the age of 50. Suicide accounted for 24% of deaths among patients with PNES in this age group. Neoplasia and cardiorespiratory causes were responsible for 51% of deaths with a known cause across all ages and 67% of those between ages 50 and 69. Among people with epilepsy, external causes accounted for 7% of all deaths. Neoplasia and cardiorespiratory causes were observed in 42% of people with epilepsy. Epilepsy was responsible for 28% of deaths with a known cause among patients with epilepsy

The research was funded by Australia’s National Health and Medical Research Council and the RMH Neuroscience Foundation.

[email protected]

SOURCE: O’Brien TJ et al. AES 2018, Abstract 1.139.

*Correction 12/4/18: An earlier version of this article misstated the name of the presenter. Russell Nightscales presented this study.

NEW ORLEANS – Among patients with psychogenic nonepileptic seizures, the risk of death is more than twice as great as among the general population, according to data presented at the annual meeting of the American Epilepsy Society. Patients with PNES have a mortality rate comparable to that of patients with drug-resistant epilepsy.

“This [finding] emphasizes the importance of correct diagnosis and identification of relevant pathologies in order to avoid preventable deaths in an important group of patients, where medical attention is often inappropriately directed to a dramatic but ultimately irrelevant clinical feature of the condition,” said Russell Nightscales, a first-year medical student at the University of Melbourne.*

Although PNES sometimes is mistaken for epilepsy and treated accordingly, it is a form of conversion disorder. The elevated risk of death among patients with epilepsy is understood, but few researchers have studied mortality in patients with PNES.

Mr. Nightscales and his colleagues conducted a retrospective cohort study of patients who had been admitted for a comprehensive epilepsy evaluation to one of two tertiary hospital video EEG monitoring (VEM) units in Melbourne between Jan. 1, 1995, and Dec. 31, 2015. The investigators ascertained mortality and cause of death by linking patient data to the Australian National Death Index (NDI). When a coroner’s report was available, they refined the cause of death using information from the National Coronial Information System. Each patient’s diagnosis was based on the consensus opinion of experienced epileptologists at the Comprehensive Epilepsy Meeting following a review of the clinical history, VEM data, and investigations. The researchers compared mortality in patients with PNES, epilepsy, or both conditions. They extracted clinical data through medical record review. Finally, they determined lifetime history of psychiatric disorders through review of neuropsychiatric reports.

Of 3,152 patients who underwent VEM, the investigators included 2,076 patients in their analyses. Of this population, 631 patients had PNES, 1,339 had epilepsy, and 106 had both. The standardized mortality ratio (SMR) among patients with PNES was 2.6 times greater than among the general population. Patients with PNES between ages 30 and 39 had a ninefold higher risk of death, compared with the general population. The SMR of patients with epilepsy was 3.2. The investigators found no significant difference in the rate of mortality between any of the patient groups after excluding 17 patients with epilepsy and a known brain tumor at the time of VEM, who had a malignant neoplasm of the brain listed as their primary cause of death.

Death resulted from external causes in 20% of all deaths among patients with PNES and in 53% of deaths with a known cause among patients who died below the age of 50. Suicide accounted for 24% of deaths among patients with PNES in this age group. Neoplasia and cardiorespiratory causes were responsible for 51% of deaths with a known cause across all ages and 67% of those between ages 50 and 69. Among people with epilepsy, external causes accounted for 7% of all deaths. Neoplasia and cardiorespiratory causes were observed in 42% of people with epilepsy. Epilepsy was responsible for 28% of deaths with a known cause among patients with epilepsy

The research was funded by Australia’s National Health and Medical Research Council and the RMH Neuroscience Foundation.

[email protected]

SOURCE: O’Brien TJ et al. AES 2018, Abstract 1.139.

*Correction 12/4/18: An earlier version of this article misstated the name of the presenter. Russell Nightscales presented this study.