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Neurologists should be aware of safety data and drug interactions.

HOUSTON—Many people with epilepsy use herbal and botanical therapies. Some patients use them to help control their seizures, while others use them to treat medication side effects or co-occurring symptoms, such as depression, anxiety, and memory problems.

“Ask your patients about the use of botanicals because they are probably using them,” said Dana Ekstein, MD, PhD, a senior neurologist at Hadassah Medical Center in Jerusalem, in an overview provided at the 70th Annual Meeting of the American Epilepsy Society. “Be ready to advise on the safety of their use.”

Dana Ekstein, MD, PhD

Efficacy and safety data for many of the treatments are limited, but educational resources are available to keep neurologists up to date. In addition, neurologists should ensure that botanicals do not interfere with conventional medication.

Widely Used

According to the 2012 American National Health Interview Survey, about a third of the population uses complementary medicine. Herbal and botanical medicines (ie, nonvitamin, nonmineral natural products) are the most commonly used complementary medicines and are used by about 18% of the population. Among people with epilepsy, studies have found that about half of adults and a third of children use complementary therapies. Patients often do not report the use of complementary medicine to their physicians, Dr. Ekstein said.

Massot-Tarrús and McLachlan examined the use of cannabis by people with epilepsy who were admitted to an epilepsy monitoring unit in Canada. More than half of them had tried marijuana. Many of them—59% of patients with epilepsy and 33% of patients with psychogenic nonepileptic seizures—used cannabis daily.Although botanicals were the mainstay of epilepsy treatment for centuries, modern data on botanicals in epilepsy are limited, Dr. Ekstein said. A 2009 Cochrane review of traditional Chinese medicine for epilepsy included only five unblinded single-center controlled studies. Although the studies reported some benefit, the probability of selection, detection, and performance bias meant that the treatment’s effect could not reliably be evaluated.

Cannabis

A 2014 Cochrane review of cannabinoids for epilepsy considered four randomized controlled trials with a total of 48 patients. Each trial included between nine and 15 patients, and investigators followed patients for between one and 12 months. The studies failed to provide efficacy evidence. In another review that considered all published studies with more than one patient, researchers analyzed eight studies with a total of 105 children and adults. Patients received placebo or cannabis compounds. Of the patients who received cannabis, 61% experienced improvement.

A retrospective trial of medical cannabis oil in Israel published in 2016 included 74 pediatric patients. Fifty-two percent of the patients had a 50% or greater reduction in seizure frequency, and one patient became seizure-free. Sixty percent of patients reported other benefits, such as improved behavior, alertness, language, communication, motor skills, and sleep.

A prospective open-label study by Devinsky et al enrolled 214 patients from 11 centers in the United States. The study included patients with drug-resistant epilepsy with onset in childhood who had at least four seizures per month. Patients received cannabidiol and were followed for three months. Of 137 patients included in the efficacy analysis, 39% had a 50% or greater reduction in seizure frequency.

Mushroom May Treat Depression

A Chinese mushroom called Xylaria nigripes has been studied for the treatment of depression in patients with epilepsy, Dr. Ekstein said. Peng et al conducted a randomized double-blind placebo-controlled trial that included 104 patients with epilepsy and depression. The mushroom significantly improved Hamilton Depression Rating Scale and quality of life scores, compared with placebo.

Although not studied in patients with epilepsy, research has shown that St. John’s wort effectively treats mild to moderate depression; kava treats generalized anxiety; and rosenroot improves attention, fatigue, mild depression, and mental performance, she said.

Safety

Many patients assume that natural products are safe, but there are important safety considerations, Dr. Ekstein said. Some botanicals have been associated with seizures, including ephedra, St. John’s wort, and ginkgo biloba. Cannabinoids, especially tetrahydrocannabinol (THC), may induce memory and executive function impairment and psychiatric symptoms. Cannabinoids also may impair plasticity in the developing brain.

Side effects in cannabis trials have been relatively common. In the retrospective Israeli trial, 46% of patients experienced adverse events (eg, seizure aggravation, somnolence, fatigue, and gastrointestinal disturbances). In the trial by Devinsky et al, 79% of patients experienced adverse events. Although most of the adverse events were mild to moderate and transient, 30% were serious adverse events (eg, status epilepticus, diarrhea, pneumonia, and weight loss).

Interactions between botanicals and antiepileptic drugs also should be taken into account, she said. Some botanicals may decrease or increase bioavailability of antiepileptic drugs. For example, cannabidiol increases concentrations of clobazam.

More clinical trials are needed to establish the efficacy and safety of botanical therapies. Cannabinoids are “on the right path” in terms of receiving further study. “There are almost no planned trials” of other botanicals, however, Dr. Ekstein said. The medical community should prioritize botanicals for further study, and neurologists should offer patients participation in clinical studies when they are available, she said.

Neurologists generally should be better educated regarding the use of botanical therapies. Online resources, such as those provided by the National Center for Complementary and Integrative Health, provide information about botanical therapies. The International League Against Epilepsy recently created the Web-based Epilepsy Naturapedia to provide information about the use of natural products in the treatment of epilepsy, Dr. Ekstein said.

 

 

Jake Remaly

Suggested Reading

Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15(3):270-278.

Ekstein D, Schachter SC. Natural products in epilepsy-the present situation and perspectives for the future. Pharmaceuticals (Basel). 2010;3(5):1426-1445.

Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst Rev. 2014;(3):CD009270.

Li Q, Chen X, He L, Zhou D. Traditional Chinese medicine for epilepsy. Cochrane Database Syst Rev. 2009;(3):CD006454.

Massot-Tarrús A, McLachlan RS. Marijuana use in adults admitted to a Canadian epilepsy monitoring unit. Epilepsy Behav. 2016;63:73-78.

Peng WF, Wang X, Hong Z, et al. The anti-depression effect of Xylaria nigripes in patients with epilepsy: A multicenter randomized double-blind study. Seizure. 2015;29:26-33.

Szaflarski JP, Bebin EM. Cannabis, cannabidiol, and epilepsy--from receptors to clinical response. Epilepsy Behav. 2014;41:277-282.

Tzadok M, Uliel-Siboni S, Linder I, et al. CBD-enriched medical cannabis for intractable pediatric epilepsy: the current Israeli experience. Seizure. 2016;35:41-44.

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Neurologists should be aware of safety data and drug interactions.
Neurologists should be aware of safety data and drug interactions.

HOUSTON—Many people with epilepsy use herbal and botanical therapies. Some patients use them to help control their seizures, while others use them to treat medication side effects or co-occurring symptoms, such as depression, anxiety, and memory problems.

“Ask your patients about the use of botanicals because they are probably using them,” said Dana Ekstein, MD, PhD, a senior neurologist at Hadassah Medical Center in Jerusalem, in an overview provided at the 70th Annual Meeting of the American Epilepsy Society. “Be ready to advise on the safety of their use.”

Dana Ekstein, MD, PhD

Efficacy and safety data for many of the treatments are limited, but educational resources are available to keep neurologists up to date. In addition, neurologists should ensure that botanicals do not interfere with conventional medication.

Widely Used

According to the 2012 American National Health Interview Survey, about a third of the population uses complementary medicine. Herbal and botanical medicines (ie, nonvitamin, nonmineral natural products) are the most commonly used complementary medicines and are used by about 18% of the population. Among people with epilepsy, studies have found that about half of adults and a third of children use complementary therapies. Patients often do not report the use of complementary medicine to their physicians, Dr. Ekstein said.

Massot-Tarrús and McLachlan examined the use of cannabis by people with epilepsy who were admitted to an epilepsy monitoring unit in Canada. More than half of them had tried marijuana. Many of them—59% of patients with epilepsy and 33% of patients with psychogenic nonepileptic seizures—used cannabis daily.Although botanicals were the mainstay of epilepsy treatment for centuries, modern data on botanicals in epilepsy are limited, Dr. Ekstein said. A 2009 Cochrane review of traditional Chinese medicine for epilepsy included only five unblinded single-center controlled studies. Although the studies reported some benefit, the probability of selection, detection, and performance bias meant that the treatment’s effect could not reliably be evaluated.

Cannabis

A 2014 Cochrane review of cannabinoids for epilepsy considered four randomized controlled trials with a total of 48 patients. Each trial included between nine and 15 patients, and investigators followed patients for between one and 12 months. The studies failed to provide efficacy evidence. In another review that considered all published studies with more than one patient, researchers analyzed eight studies with a total of 105 children and adults. Patients received placebo or cannabis compounds. Of the patients who received cannabis, 61% experienced improvement.

A retrospective trial of medical cannabis oil in Israel published in 2016 included 74 pediatric patients. Fifty-two percent of the patients had a 50% or greater reduction in seizure frequency, and one patient became seizure-free. Sixty percent of patients reported other benefits, such as improved behavior, alertness, language, communication, motor skills, and sleep.

A prospective open-label study by Devinsky et al enrolled 214 patients from 11 centers in the United States. The study included patients with drug-resistant epilepsy with onset in childhood who had at least four seizures per month. Patients received cannabidiol and were followed for three months. Of 137 patients included in the efficacy analysis, 39% had a 50% or greater reduction in seizure frequency.

Mushroom May Treat Depression

A Chinese mushroom called Xylaria nigripes has been studied for the treatment of depression in patients with epilepsy, Dr. Ekstein said. Peng et al conducted a randomized double-blind placebo-controlled trial that included 104 patients with epilepsy and depression. The mushroom significantly improved Hamilton Depression Rating Scale and quality of life scores, compared with placebo.

Although not studied in patients with epilepsy, research has shown that St. John’s wort effectively treats mild to moderate depression; kava treats generalized anxiety; and rosenroot improves attention, fatigue, mild depression, and mental performance, she said.

Safety

Many patients assume that natural products are safe, but there are important safety considerations, Dr. Ekstein said. Some botanicals have been associated with seizures, including ephedra, St. John’s wort, and ginkgo biloba. Cannabinoids, especially tetrahydrocannabinol (THC), may induce memory and executive function impairment and psychiatric symptoms. Cannabinoids also may impair plasticity in the developing brain.

Side effects in cannabis trials have been relatively common. In the retrospective Israeli trial, 46% of patients experienced adverse events (eg, seizure aggravation, somnolence, fatigue, and gastrointestinal disturbances). In the trial by Devinsky et al, 79% of patients experienced adverse events. Although most of the adverse events were mild to moderate and transient, 30% were serious adverse events (eg, status epilepticus, diarrhea, pneumonia, and weight loss).

Interactions between botanicals and antiepileptic drugs also should be taken into account, she said. Some botanicals may decrease or increase bioavailability of antiepileptic drugs. For example, cannabidiol increases concentrations of clobazam.

More clinical trials are needed to establish the efficacy and safety of botanical therapies. Cannabinoids are “on the right path” in terms of receiving further study. “There are almost no planned trials” of other botanicals, however, Dr. Ekstein said. The medical community should prioritize botanicals for further study, and neurologists should offer patients participation in clinical studies when they are available, she said.

Neurologists generally should be better educated regarding the use of botanical therapies. Online resources, such as those provided by the National Center for Complementary and Integrative Health, provide information about botanical therapies. The International League Against Epilepsy recently created the Web-based Epilepsy Naturapedia to provide information about the use of natural products in the treatment of epilepsy, Dr. Ekstein said.

 

 

Jake Remaly

Suggested Reading

Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15(3):270-278.

Ekstein D, Schachter SC. Natural products in epilepsy-the present situation and perspectives for the future. Pharmaceuticals (Basel). 2010;3(5):1426-1445.

Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst Rev. 2014;(3):CD009270.

Li Q, Chen X, He L, Zhou D. Traditional Chinese medicine for epilepsy. Cochrane Database Syst Rev. 2009;(3):CD006454.

Massot-Tarrús A, McLachlan RS. Marijuana use in adults admitted to a Canadian epilepsy monitoring unit. Epilepsy Behav. 2016;63:73-78.

Peng WF, Wang X, Hong Z, et al. The anti-depression effect of Xylaria nigripes in patients with epilepsy: A multicenter randomized double-blind study. Seizure. 2015;29:26-33.

Szaflarski JP, Bebin EM. Cannabis, cannabidiol, and epilepsy--from receptors to clinical response. Epilepsy Behav. 2014;41:277-282.

Tzadok M, Uliel-Siboni S, Linder I, et al. CBD-enriched medical cannabis for intractable pediatric epilepsy: the current Israeli experience. Seizure. 2016;35:41-44.

HOUSTON—Many people with epilepsy use herbal and botanical therapies. Some patients use them to help control their seizures, while others use them to treat medication side effects or co-occurring symptoms, such as depression, anxiety, and memory problems.

“Ask your patients about the use of botanicals because they are probably using them,” said Dana Ekstein, MD, PhD, a senior neurologist at Hadassah Medical Center in Jerusalem, in an overview provided at the 70th Annual Meeting of the American Epilepsy Society. “Be ready to advise on the safety of their use.”

Dana Ekstein, MD, PhD

Efficacy and safety data for many of the treatments are limited, but educational resources are available to keep neurologists up to date. In addition, neurologists should ensure that botanicals do not interfere with conventional medication.

Widely Used

According to the 2012 American National Health Interview Survey, about a third of the population uses complementary medicine. Herbal and botanical medicines (ie, nonvitamin, nonmineral natural products) are the most commonly used complementary medicines and are used by about 18% of the population. Among people with epilepsy, studies have found that about half of adults and a third of children use complementary therapies. Patients often do not report the use of complementary medicine to their physicians, Dr. Ekstein said.

Massot-Tarrús and McLachlan examined the use of cannabis by people with epilepsy who were admitted to an epilepsy monitoring unit in Canada. More than half of them had tried marijuana. Many of them—59% of patients with epilepsy and 33% of patients with psychogenic nonepileptic seizures—used cannabis daily.Although botanicals were the mainstay of epilepsy treatment for centuries, modern data on botanicals in epilepsy are limited, Dr. Ekstein said. A 2009 Cochrane review of traditional Chinese medicine for epilepsy included only five unblinded single-center controlled studies. Although the studies reported some benefit, the probability of selection, detection, and performance bias meant that the treatment’s effect could not reliably be evaluated.

Cannabis

A 2014 Cochrane review of cannabinoids for epilepsy considered four randomized controlled trials with a total of 48 patients. Each trial included between nine and 15 patients, and investigators followed patients for between one and 12 months. The studies failed to provide efficacy evidence. In another review that considered all published studies with more than one patient, researchers analyzed eight studies with a total of 105 children and adults. Patients received placebo or cannabis compounds. Of the patients who received cannabis, 61% experienced improvement.

A retrospective trial of medical cannabis oil in Israel published in 2016 included 74 pediatric patients. Fifty-two percent of the patients had a 50% or greater reduction in seizure frequency, and one patient became seizure-free. Sixty percent of patients reported other benefits, such as improved behavior, alertness, language, communication, motor skills, and sleep.

A prospective open-label study by Devinsky et al enrolled 214 patients from 11 centers in the United States. The study included patients with drug-resistant epilepsy with onset in childhood who had at least four seizures per month. Patients received cannabidiol and were followed for three months. Of 137 patients included in the efficacy analysis, 39% had a 50% or greater reduction in seizure frequency.

Mushroom May Treat Depression

A Chinese mushroom called Xylaria nigripes has been studied for the treatment of depression in patients with epilepsy, Dr. Ekstein said. Peng et al conducted a randomized double-blind placebo-controlled trial that included 104 patients with epilepsy and depression. The mushroom significantly improved Hamilton Depression Rating Scale and quality of life scores, compared with placebo.

Although not studied in patients with epilepsy, research has shown that St. John’s wort effectively treats mild to moderate depression; kava treats generalized anxiety; and rosenroot improves attention, fatigue, mild depression, and mental performance, she said.

Safety

Many patients assume that natural products are safe, but there are important safety considerations, Dr. Ekstein said. Some botanicals have been associated with seizures, including ephedra, St. John’s wort, and ginkgo biloba. Cannabinoids, especially tetrahydrocannabinol (THC), may induce memory and executive function impairment and psychiatric symptoms. Cannabinoids also may impair plasticity in the developing brain.

Side effects in cannabis trials have been relatively common. In the retrospective Israeli trial, 46% of patients experienced adverse events (eg, seizure aggravation, somnolence, fatigue, and gastrointestinal disturbances). In the trial by Devinsky et al, 79% of patients experienced adverse events. Although most of the adverse events were mild to moderate and transient, 30% were serious adverse events (eg, status epilepticus, diarrhea, pneumonia, and weight loss).

Interactions between botanicals and antiepileptic drugs also should be taken into account, she said. Some botanicals may decrease or increase bioavailability of antiepileptic drugs. For example, cannabidiol increases concentrations of clobazam.

More clinical trials are needed to establish the efficacy and safety of botanical therapies. Cannabinoids are “on the right path” in terms of receiving further study. “There are almost no planned trials” of other botanicals, however, Dr. Ekstein said. The medical community should prioritize botanicals for further study, and neurologists should offer patients participation in clinical studies when they are available, she said.

Neurologists generally should be better educated regarding the use of botanical therapies. Online resources, such as those provided by the National Center for Complementary and Integrative Health, provide information about botanical therapies. The International League Against Epilepsy recently created the Web-based Epilepsy Naturapedia to provide information about the use of natural products in the treatment of epilepsy, Dr. Ekstein said.

 

 

Jake Remaly

Suggested Reading

Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15(3):270-278.

Ekstein D, Schachter SC. Natural products in epilepsy-the present situation and perspectives for the future. Pharmaceuticals (Basel). 2010;3(5):1426-1445.

Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst Rev. 2014;(3):CD009270.

Li Q, Chen X, He L, Zhou D. Traditional Chinese medicine for epilepsy. Cochrane Database Syst Rev. 2009;(3):CD006454.

Massot-Tarrús A, McLachlan RS. Marijuana use in adults admitted to a Canadian epilepsy monitoring unit. Epilepsy Behav. 2016;63:73-78.

Peng WF, Wang X, Hong Z, et al. The anti-depression effect of Xylaria nigripes in patients with epilepsy: A multicenter randomized double-blind study. Seizure. 2015;29:26-33.

Szaflarski JP, Bebin EM. Cannabis, cannabidiol, and epilepsy--from receptors to clinical response. Epilepsy Behav. 2014;41:277-282.

Tzadok M, Uliel-Siboni S, Linder I, et al. CBD-enriched medical cannabis for intractable pediatric epilepsy: the current Israeli experience. Seizure. 2016;35:41-44.

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