Regional
Epilepsy Center
Seattle, Washington,
USA
(206)744-3576 or
(1-800-374-3627)
The widespread use of herbal remedies is not surprising. Pesticide laden mass marketed produce has fallen out of favor while organic foods are in vogue. Plastic bottles are out of fashion, while glass is thought to be less toxic. Many of us, if we could afford it, would readily change our consumables to more wholesome natural varieties. Organic apples have fewer pesticides, and may even taste better than the mass produced kind. Why not then extend this natural approach to treatments for medical conditions? If organic apples are better, the natural approach to relieving our ailments must also be better, right? After all, taking a drug, whether prescribed by a physician, bought over the counter, or dispensed by an herbalist, is an act of faith. Any rational person can have healthy skepticism of what modern medicine can accomplish.
The public, with some justification, is convinced modern medicine is good at treating acute severe problems like infection, but not so good at treating and preventing chronic medical conditions such as chronic back pain. Epilepsy, by its nature, straddles this
divide. Some patients use complementary and alternative medicines (CAM) in the hope that they will control their seizures. Other patients use them in an attempt to cope with comorbid conditions, including some medication related side effects. It is not uncommon for patients to use herbal treatments for lack of energy, depression, or sleep problems.
Patients often do not mention their herbal drug use to their physicians. Sometimes these alternative treatments are not thought to be medically relevant or may simply be forgotten during a rushed appointment. Others undoubtedly do not mentioning use of CAM because they feel their physician would not approve. We, as physicians, are also often uncomfortable talking about natural remedies. When a patient asks about herbal remedies, we may be dismissive, answer in broad uninformative yet discouraging terms, or simply expose our ignorance (“don’t know”). Our lack of comfort partly stems from limited coverage of such topics in medical literature. However, the bigger problems are lack of substantiated studies, non-standardized products, and an herbal industry that operates more on myth than scientific rigor. As I can also attest from reviewing the literature, most herbal remedies are backed up only by spotty and anecdotal evidence.
Nevertheless, epilepsy brings patients back to us who seek our advice. The following offers a brief summary of possible answers to some of the most common questions:
“Are there any SAFE natural or alternative treatments that can cure my epilepsy without medications or surgery?”
Epilepsy, like most chronic medical conditions, is often treated symptomatically, by treating clinical seizures. Seizures occur intermittently so their control is a test of observer patience. Some patients have an underlying curable cause, which often means an epileptic focus amenable to brain surgery such as a tumor or mesial temporal sclerosis. Most other patients are not cured at all. Many patients may enter periods of remission while on drugs. Sometimes, the seizures disappear altogether and do not recur when medication is withdrawn--there are certainly some younger patients who “outgrow” their epilepsy. For most patients the most realistic hope is not a “cure”, but complete seizure control while on medication, often life long.
The ketogenic diet is the only non-medication/non-surgical treatment shown to be effective in some patients (1). It may reduce in some and rarely control seizures completely, but it does not treat or cure the underlying epilepsy. This diet has adverse effects (2) and is hard to follow. Adherence to the diet is difficult for anyone with free access to vending machines, or a refrigerator. It is sometimes offered to young children whose access to food can be controlled more strictly. The long-term safety of the diet has not been adequately studied in adults. Some limited cases series suggest, but certainly do not prove, that a modified Atkins diet may be helpful (3).
The other non-pharmacological approach is to implant a vagal nerve stimulator. This is not non-invasive and reduces seizures in some patients but rarely eliminates them.
“I want to try such-and-such non-pharmacological treatment for my epilepsy. Is it safe or effective?”
The short answer to both questions is “don’t know”. In truth, some approaches are so benign that they cannot be too harmful even if their efficacy is unproven. These methods include relaxation techniques (4), yoga (5), hypnosis, acupuncture (6), biofeedback, and others that promise to provide patients with some degree of control using body’s natural powers to produce a mild reduction in seizure symptom (7) and even use of magnets have reported risk of seizures. These anecdotal reports hardly “prove” that these modalities accomplish any biological result. Rather, they point to the weakness of anecdotal evidence to demonstrate effects of unproven remedies.
“I want to try such-and-such herbal or natural treatment for my epilepsy. Is it safe?”
There are many reports of use of herbal and natural remedies for epilepsy but evidence of efficacy is lacking. Some agents have significant potential for harm. Fortunately, resources are now available to clinicians to review the basics of some herbal remedies. I have mostly used the Natural Medicine Database for this review (8) although a number of other good resources are available (references at bottom of article). Any promises of efficacy should be verified thoroughly. Given lack of safety data about effects on children and risk of teratogenic potential, herbal remedies should be avoided in children and women of child bearing potential.
For many drugs appropriate safety data is entirely lacking. Several remedies suggested for epilepsy are frankly poisonous, even in small quantities. Table 1 lists some substances with reported risk of toxicity. These drugs should be avoided altogether. For other remedies with scant proof of safety or efficacy (Table 2), a similar cautious approach is best warranted. Other substances may be more widely used but have been reported to be rarely, but fatally, toxic, and are listed in Table 3.
A number of other herbal remedies are somewhat more ubiquitous and appear safe on the surface. Many have been used in traditional remedies for hundreds of years. Others include remedies that occur in dietary consumed herbs or naturally present in small quantities in our diet. FDA, for example, assigns a designation “GRAS” for some substances “Generally Regarded As Safe” without formal safety testing, although this designation is made with some additional comments or specified to be for a particular use. Nevertheless, some of the same substances potentially have toxic effects at higher doses. A good example is the ubiquitous caffeine that, while safe for most people, can in extremely high doses be fatal (9). Caffeine at sublethal doses can also exacerbate seizures (10), a risk that is very low but is hard to quantify for individuals. The same can be said of many vitamins and herbs. Many common herbs, for example, contain minute amounts of toxic substances. Essential oils of these herbs can exacerbate seizures or even be fatal. Table 4 lists many herbal treatments and supplements that are thought to carry risk of toxicity at high doses. A number of herbal drugs can also exacerbate seizures. Table 6 lists remedies that are thought to increase seizure frequency in some patients. Curiously, some of the remedies in the table are also the ones purported to be helpful in some epilepsy syndromes. This is not surprising. Among the traditional epilepsy medication, for example, we know that carbamazepine may make absence seizures worse, or diazepam can cause some Lennox-Gastaut patients to have more drop attacks. Unfortunately for herbal remedies, the anecdotal reports of efficacy do not describe the seizure types for which the herb is said to help (e.g. complex partial vs. generalized onset seizures).
Making matters more complicated are the pharmacological interactions of herbal preparations. Many herbal remedies (particularly some of the popular ones that appear first on Google searches) appear to mediate their effect via binding to GABAA receptors, suggesting that these substances could have effects similar to barbiturates and benzodiazepines and raise theoretical concerns (see section below). The first concern is pharmacodynamic interaction with GABAA modulators, such as lorazepam, diazepam or phenobarbital, that could exacerbate adverse effects. The second concern is that many GABAA active drugs produce tolerance, are habit forming and pose a risk of withdrawal seizures. While this effect has not been proved for most herbal remedies, one has to exercise caution in starting and stopping the herbal remedies abruptly, particularly after prolonged use. It is not surprising that most anecdotal studies of benefits of these herbal remedies only report short term efficacy data but not test long term results. Table 5 lists some herbal remedies that have GABAA-ergic effects. The possible pharmacokinetic drug interactions of herbal remedies are discussed separately below.
It should not be assumed that all herbal remedies are pure and of appropriate quality. These substances are, in general, not tested to prove they contain what they promise, and purity data is usually not available. There are cases where remedies have contained toxic substances (lead, mercury and arsenic, 11,12) or toxic herbs of similar appearance. Some recent studies have identified traditional preparations that contained common antiepileptic drugs (often phenytoin or phenobarbital) at inappropriate doses (13).
Having said that, there are reputable suppliers of many supplements. Products from countries where herbal industry is regulated (such as Germany) may also be more certain to contain the promised ingredients. Plants, however, do not heed government regulation and often produce different levels of active substances. The differences not only appear among different growers, but also may depend on whether leaves are harvested in fall, spring or summer, or whether the plant is grown in shade or full sun. There are also many reports that some of the desired active compounds may be concentrated in the packaging and drying process while others are destroyed. Therefore, the therapeutic and toxic effects of a dose of a herbal preparation may be differ significantly among various preparations.
The bottom line is many of us find it unethical to prescribe herbs with uncertain pharmacological and therapeutic properties when there are known medicines that do not have these disadvantages. Herbal remedies should not ever be used for first line treatment of epilepsy.
I have symptom x and want to use the natural treatment Y to help relieve it. Given my epilepsy, is it safe to do so?
I probably have someone calling with this question every month. Given the number of available herbal medicines and the number of seizure drugs, mentioning every possibility is rather hard. The lack of adequate safety, efficacy or pharmacological effects of herbal and alternative remedies already mentioned, is the main issue. Most pertinent is inadequate information on whether any of these remedies have the potential to make seizures worse.
Assuming the preparations are not frankly toxic, the main concerns, similar to discussion above still include toxicity, risk of seizure exacerbation, and pharmacological interactions. Again Tables 1-6 above summarize the areas of concern. Herbal drugs can certainly have harmful interactions with antiepileptic drugs by pharmacokinetic interaction. Some of these are listed in Table 7.
Substances used for depression include St. John’s Wort, SAMe, and 5-hydroxytryptophan (5HTP). Hyperforin, the main active ingredient of St. John’s Wort induces Cytochrome P450 (Cyp) 3A4 isozyme and the p-glycoprotein transporter resulting in several clinically significant drug interactions. St Johns Wort is the most common herb involved in suspected herbal drug interactions. However there are no clinically significant interactions with AEDs. Even though carbamazepine is metabolize by CYP3A4, carbamazepine auto-induces CYP3A4 itself; and addition of St. John’s Wort does not increases the induction. Little is know of the interaction of SAMe with epilepsy. 5HTP in one preparation was associated with fatal eosinophylia-myalgia syndrome. It may cause seizures in some populations (e.g.. Down’s Syndrome, 15).
Among the sedative/hypnotics, valerian is commonly used to treat anxiety and induce sleep and has a reasonable safety track record in short term use, with a large number of patient exposures. It even carries the “GRAS” designation. However, when valerian is used to treat epilepsy, there are some concerns. It may have significant GABA effects (16). It may also partially block the p450 pathway with a risk of drug interaction. Kava, another herbal anxiety treatment, may also have significant GABA effects (17). There is also evidence of tolerance to this herb and rare risk of liver toxicity in chronic use (18). Acute toxicity has been reported when kava is used with other sedatives such as lorazepam or alcohol (19). Passionflower, another herbal sedative, is similarly thought to have effects on the GABA pathway (20). There are reports of rare life threatening toxicity from this herbal remedy as well, including cases of vasculitis (21) and cardiac abnormalities (22). And then there is ethanol, which while not prescribed by herbal practitioners, belongs in this family, albeit with even a higher risk. These sedative herbs, while reported to have benefits for seizures, are not shown to be effective for epilepsy and all carry risks if used long term. Nevertheless, not including the concerns noted above, there is also little evidence for harm from these herbs used for anxiety or sleep if used occasionally, on an as needed basis, at modest doses, and in patients at low risk for drug interactions.
Stimulants and other cognitive enhancers, by contrast, are more likely to exacerbate seizures and pose problems with drug interactions. They may be used by epilepsy patients in an attempt to treat the cognitive problems associated with seizures and antiepileptic drugs. The stimulant ephedra (Chinese Ma Huang) has, in several cases, been reported to precipitate seizures (23). Coca (a source of cocaine) may also result in seizures. The effects of coffee and tea are probably modest due to the very small doses of active substances, theopholine, theobromine, and caffeine, in these beverages. However, risks may be present with large overdoses or when these are combined with other stimulants such as ephedra (24). The cognitive “enhancer” ginko biloba has been said associated with seizures (25,26) but this is not well documented. Ginko biloba is also suspected of having effects on antiepileptic drug metabolism, although this effect is also uncertain. There are some real concerns about effects of ginseng on the drug metabolism of warfarin, a drug also metabolized by the p450 system. Whether this interaction occurs in the p450 isozyme relevant to antiepileptic drugs or via other mechanism, is unclear Many herbal products have been shown to effect the drug metabolism via the cytochrome 450 isozymes when studied in vitro. However, the majority of the interaction do not translate to clinically significant interaction in vivo.
I tried a natural remedy for a while for my seizures and it seemed to work. Can you prescribe it for me?
I get this question most commonly regarding marijuana. Many users of cannabis feel that their seizures are less significant when they smoke it. The data on long term toxicity of smoked marijuana in adults is well known (probably worse than cigarettes, but not as bad as chronic heavy alcohol use). There are more significant concerns about its use in teenagers (and probably young adults). Paranoia, and effects on mood and motivation are quite concerning. Data on short-term effects on seizures are mixed, as it reportedly is helpful in some, but may make seizures worse in others (27). Long term safety and efficacy data for epilepsy are lacking. Given the rates of depression, other psychiatric problems such as paranoia, and unemployment among epilepsy patients, one should show extreme caution in advocating use of marijuana in this population. Most of us discourage its use, and I do not prescribe it.
This question also comes up regarding one of the non-pharmacological alternative treatments discussed above. In particular we occasionally have to fill out a statement of need and candidacy for a service dog to aid in seizures. Further, some insurance companies may pay for biofeedback training if it is prescribed by a health care provider. While I am not sold on the benefits of these interventions, I think they are safe enough for a patient to try. They are likely not cost effective, however.
I may need to take my seizure drugs for life. Do I need to take/avoid any supplements to prevent/alleviate other health problems in the future? Are there any foods to avoid or consume?
Here, there is probably more information than patients recognize. I usually spend a large portion of my initial visit going over some of these concerns. First, some healthy habits may be useful. Most importantly, lack of sleep and chronic stress (28) are likely harmful for epilepsy. Who could argue against a healthy diet, adequate sleep, or exercise? Many other substances are best avoided. The effects of alcohol use—its interaction with seizure drugs, risks of seizure exacerbation and liver toxicity are well known to clinicians. There may also be effects on the metabolism of seizure drugs if used regularly. The harms of smoked tobacco and marijuana are higher in patients with epilepsy, due to the additional risk of loss of bone density and gum disease, particular when combined with phenytoin. Cocaine and amphetamines carry risk of seizures. Caffeine intake may be unhelpful at high doses.
All women of child bearing age with epilepsy are encouraged to take supplemental folic acid. This is due to concerns about the overlapping associations: 1) a higher incidence of neural tube defects in fetuses of women with epilepsy than other women (29), 2) a higher incidence of neural tube defects in women with low dietary folic acid (30), and 3) some seizure medications are folic acid antagonists (31). Note that the critical issue of whether folic acid supplementation reduces rates of birth defects in the offspring of epilepsy patients is unanswered. Nevertheless, many of us advocate at least 400 mcg daily (the amount in a prenatal multivitamin) to as much as 4 mg bid (doses used safely in treatment of folate deficiency associated neural tube defects).
Whether other groups of patients benefit from folate supplementation is unknown. There is a higher risk of strokes and heart disease in epilepsy patients than in general public (32). This risk is associated with elevated blood levels of homocysteine (33) that may possibly be reduced by folate supplementation. It is unproven whether folate supplements would lead to better cardiovascular health in patients. Nevertheless, low dose supplementation might be helpful and carries little risk.
A concern is that folate supplements may delay diagnosis of B12 deficiency by masking megaloblastic anemia until neurological symptoms of B12 deficiency develop. Whether patients should be screened for B12 deficiency, when on folate, is unclear, but this is unlikely to be cost effective. A simple substitution of B-complex for just straight folic acid pills would not alleviate this concern because pernicious anemia is most often due to problems with absorption of the vitamin, rather than dietary deficiency.
Anecdotally, some patients report fewer side effects from their antiepileptic drugs when given B-vitamins. It has been claimed that pyridoxine may alleviate irritability from levetiracetam (34). Also, riboflavin has been advocated for prophylaxis for migraines (35), a common problem among epilepsy patients. As mentioned earlier, these supplements are safe at low doses.
The need for supplementation of other vitamins in patients with epilepsy is a bit unclear. Older literature has suggested low vitamin E and D levels, but it is unclear if this is significant. Whether a multivitamin is sufficient or even necessary is unknown. Given the high incidence of osteopenia, use of vitamin D and calcium is probably prudent. A related concern is structural bone weakness in patients with epilepsy. This may be measured as osteopenia using DEXA (x-ray bone densitometry). However, bones may also be of lower quality without frank osteopenia. For example, the diameter of axial bones may be reduced in patients who develop epilepsy at a young age. Weight bearing exercise and sunshine may help in building stronger bones. Exercise may have the additional benefit of warding off depression and seasonal affective disorder.
For some other patients on particular drugs, certain nutritional supplements may be helpful. For example, levocarnitine levels may be low in patients on valproic acid (36). Patients with progressive epilepsy syndromes may also have problems with mitochondrial function. There are some dietary supplements that may help with these conditions. In these cases, however, there are potentials for high costs and even toxicity. Levocarnitine supplements, for example, may be associated with increased risk of seizures. These supplements with a more narrow benefit then should be treated like any other prescribed drug: started one at a time under a physician’s guidance, titrated slowly with the hope of achieving a particular measurable response. Fortunately, the data for safety, efficacy and these supplements, is generally of higher quality.
Lastly some foods at typical consumed quantities have potential for drug interaction with seizure drugs. Grapefruit juice, in particular, contains substances that inhibit one primary CYP isozyme, CYP3A4 and may lead to toxicity of carbamazepine (38). However, none of the other AEDs are significantly affected by this interaction.
I only want natural remedies for my epilepsy. Is there any effective natural remedy you can offer me?
Some patients, unfortunately, simply lack faith in the practice of western medicine. The short answer to this question is no, there are no proven natural remedies effective for epilepsy. No herbal remedies have been proven to be efficacious for epilepsy, particularly for long-term use. Sure, many antiepileptic drugs have short and long term toxicity and side effects, but there is no proof of safety for natural remedies at pharmacological doses, either.
Several natural remedies are listed as having “possible” or “proven” efficacy in the Natural Medicine Database. On close inspection, these treatments have only a small window of relevance. Pyridoxine is useful for the rare infant with pyridoxine dependent epilepsy (39,40). The use of N-acetylcystene (mucomyst) is supported by only a small case series in a single family of patients suffering from Unverricht-Lundborg disease (41). Medium chain triglycerides, a group of naturally occurring fatty acid derivatives, have been thought to be helpful for patients with epilepsy (42), with as many as 55 patients obtaining benefit in one study. In the late 1980’s, however, it was discovered that patients who had been on the diet for more than 2 years were developing liver abnormalities (43), leading to the diet falling somewhat out of favor, although it is still sometimes used.
So, what to do with the patient who refuses to take Western medicine based on a philosophical opposition to modern medicine? One may try to reconcile the Western medicine with their beliefs. In any case, the physician’s responsibility is to inform the patient about safety concerns, drug interactions and adverse effects of herbal products, and the lack of adequate evidence that these agents are effective for treating epilepsy, which is a dangerous condition.
Legend:
* Mentioned as a remedy for seizures or epilepsy.
+ Mentioned as a “cognitive booster”
# Mentioned as a memory enhancer / dementia treatment
@ Mentioned as an adult attention deficit disorder treatment
$ Mentioned for mood and for depression
= Mentioned as an aid to anxiety or sleep.
& Supplements used in epilepsy
1 Used for premenstrual syndrome symptoms
Table 1: Herbal seizure remedies that may be poisonous even in small doses
Table 2: Herbal drugs without much published safety data
Table 3: Herbal remedies with rare but life threatening toxicity
Table 4: Remedies with toxicity risk noted for high doses
Table 5: Drugs with potential effects on GABA receptors
Table 6: Herbal remedies with risk of seizures at pharmacological doses
Table 7: Herbal-Drug Interactions
Table 1: Herbal Seizure Remedies That May be Poisonous Even in Small Doses
ACKEE * |
Unripe fruit causes Jamaican Vomiting Illness (with severe hypoglycemia). Fruit is Banned in US. |
AMERICAN HELLEBROE * |
Cardiac depression and blockade of cardiac sodium channels. Risk of death. |
BLUE COHOSH* |
Constricts arteries with risk of cardiac infarcts, congestive heart failure, strokes, and birth defects. |
BUTANEDIOL |
Converts to GHB (gamma hydroxybutyrate). |
CALABAR BEAN* |
Cardiac toxicity (was used in rituals to detect lies – if you lived you were believed to have told the truth). |
CALOPTROPIS* |
Cardiac toxicity. Risk of convulsions. |
DIGITALIS* |
Cardiac toxicity |
EUROPEAN MISTLETOE * |
Safety concern for high doses (see Table 4) |
GBL |
Similar to GHB. Illegal. |
GHB |
Illegal and toxic (available as prescription drug for narcolepsy). |
GROUNDSEL* |
Contains toxin Hepatotoxic PA agent, which causes severe venous occlusive disease (some commercial preparations, of unverified safety, claim to be Hep PA free). Risk is higher in patients taking hepatic enzyme inducing drugs. |
HEMLOCK* |
A known poison causing paralysis due to neurotoxicity at neuromuscle junctions. |
LEVANT BERRY* |
Contain picrotoxin: GABA-A antagonist with high seizure risk. |
LILY-OF-THE-VALLEY* |
Risk of cardiac toxicity. |
OLEANDER* |
Risk of cardiac toxicity. |
PICROTOXIN |
GABA-A antagonist with high seizure risk. |
YEW* |
Considered poisonous: a single berry has been known to be fatal. |
Table 2: Herbal Drugs Without Much Published Safety Data
BETONY * |
Risk of low blood pressure |
BUPLEURUM * |
|
BURNING BUSH* |
Rare reports of poisoning. |
CHINESE CLUB-MOSS+ |
Used as “cognitive booster.” Risk of Seizures |
INDIAN LONG PEPPER* |
Active compound also found in small amounts in white and black pepper. Long history of use in ayuverdic medicine |
LADY'S BEDSTRAW* |
|
MUGWORT* |
|
SKULL CAP* |
|
STRUNTIUM* |
Unknown safety of doses above 680 mg daily. Present in smaller doses in food supply and used medically. |
TREE OF HEAVEN* |
|
Table 3: Herbal Remedies with Rare But Life Threatening Toxicity
AMERICAN ELDER* |
Parts of plant are toxic |
BAIKAL SKULLCAP* |
Few reports of liver toxicity and bone marrow dysfunction (decreased white blood cell count) |
DRUMSTICK TREE* |
Leaves, fruit, and seed are commonly used as food; however, the root and root extract cause fatal paralysis |
GOTU KOLA = + $ |
Rarely cause liver toxicity |
KAVA = + $ |
Reports of liver toxicity |
PASSIONFLOWER * |
Reports of vasculitis (related to brand Relaxim) and another reports of cardiac toxicity (prolonged QT and non-sustained ventricular tachycardia). Related plants contain known cardiac, hepatic and pancreatic toxins. |
Table 4: Remedies with Toxicity Risk Noted for High Doses
ALOE * |
Toxic to kidneys |
BORAGE |
Theoretical risk that essential oil constituent (gamma linoic acid, GLA, an omega-6 fatty acid) may increase seizure |
BETA-CAROTENE * |
Long term high dose use via supplements associated with risk of various cancers |
CAFFEINE + |
Theoretical risk of seizures at high doses. Cardiac toxiciry at high doses (overdose attempts with caffeine pills). |
CHOLINE * $ @ # |
A vitamin like substance. Naturally occurs in food and is now added to infant formulas. Concern over safety at high doses. |
COCA *+ |
Due to cocaine. |
EUROPEAN MISTLETOE* |
Toxicity at less than 3 berries or 2 leaves: reports of seizures, low blood pressure, low heart rate and death. |
EVENING PRIMROSE |
Theoretical risk that essential oil may increase seizure risk in susceptible patient thought to be due to GLA (gamma linoic acid). |
GINKO BILOBA+ # |
Seizures due to ginkotoxin, which is present at different concentrations in different formulations. |
GAMMA LINOIC ACID |
In animal models increases seizure risk. |
LITHIUM * |
Unsafe if used inappropriately. May make some seizures worse (unclear if helpful in other cases). Risk of neurological side effects higher if used with phenytoin and carbamazepine (sodium channel blockers). |
MEDIUM CHAIN TRIGLYCERIDES* |
Prolonged exposure at therapeutic doses associated with liver abnormalities. |
PYRIDOXINE * |
Unsafe at high doses due to neuropathy (above 1000mg daily) |
ROSEMARY |
Contain thujone: risk of cardiac toxicity, CNS depression and seizures. Essential oils may be fatal. |
SAGE + # $ @ |
Contain thujone: risk of cardiac toxicity, CNS depression and seizures. Essential oils may be fatal. |
SKUNK CABBAGE * |
Risk of kidney stones due to high oxalate content. |
STAR ANISE (CHINESE) |
Theoretical concern due to similarity of substances (veanistatins A, B, and C) to Anistatin found in Japanese variety of STAR ANISE which causes seizures. |
STORAX * |
Generally regarded as safe at low doses. Toxic to kidneys in large amounts |
STRONTIUM * |
Poisoning and effects on bone density with long term high dose use. |
TANSY * |
Contain thujone: risk of cardiac toxicity, CNS depression and seizures. Essential oils may be fatal. |
VINPOCETINE * # |
Risk of anticoagulation. |
VITAMIN E * |
Risk of anticoagulation. |
WORMWOOD |
Contain thujone: risk of cardiac toxicity, CNS depression and seizures. Essential oils may be fatal. |
Table 5: Drugs with Potential Effects on GABA Receptors
BAIKAL SKULLCAP * |
Contains flavonoids baicalin, baicalein, wogonin, and scutellarein. These all appear to bind to GABAA receptors with possibly benzodiazepine-like effects |
CHAMOMILE = |
One substance, apigenin, has high affinity binding to GABAA receptors. So far, this does not appear relevant to epilepsy. |
GINKO BILOBA + |
An active substance, ginkotoxin, directly binds GABAA receptors |
GOTU KOLA * |
GABAA activity postulated as part of mechanism |
KAVA = |
|
LEVANT BERRY*+$ |
Contains a known GABAA inhibitor substance: Picrotoxin. Risk of seizures. |
PASSIONFLOWER * + = @ |
Possible effects on GABAA receptors- unclear but possible interaction with other sedatives |
SKULL CAP * |
Thought to be a GABAA agonist |
STORAX * |
Several constituents may have effects on GABAA receptor. |
VALERIAN * = $ + @ |
Effects likely due to some GABA-related effects. Contains GABA and may inhibit its degradation or enhance binding to its receptors. |
Table 6: Herbal Remedies with Risk of Seizures at Pharmacological Doses
5HTP $ |
About a 15% risk of seizures reported in children with Downs Syndrome. Other (animal) data suggests it could be helpful in some cases. |
ACETYL-L-CARNITINE + # |
Theoretical risk due to similarity with L-carnitine |
COCA * + |
Risk of seizures due to trace cocaine |
DEANOL + @ |
Risk of GTC likely for high doses only |
EDTA |
Chelating agent (e.g. lead toxicity) carries a risk of seizures |
EPHEDRA + |
One of the most common cause of drug induced seizures. |
EUCALYPTUS |
Case report (other herbs involved) |
EVENING PRIMROSE OIL |
Case reports of seizures |
FOLIC ACID & |
Theoretical risk at high doses (e.g. 32 mg/day) |
GINKO BILOBA+ # |
Seizures due to ginkotoxin (MPN or 4-O-methylpyridoxine), which is present at different concentrations in different preparations and some other herbs. |
GLUTAMINE |
Theoretical |
GROUND IVY |
Known Risk of seizures |
HYPERZINE A |
Theoretical risk of exacerbation |
HYSSOP |
Known Risk of seizures |
L-CARNITINE & |
Theoretical Risk of Seizure Exacerbation |
LITHIUM * $ |
May make some seizures worse, toxicity increased with sodium channel blockers. |
LEVANT BERRY* |
Contains a known GABA inhibitor substance: Picrotoxin. Risk of seizures. |
MARIJUANA * |
Mixed effects. Some patient report improved seizure control, others may have worsening. Effects are likely modest. |
MELATONIN * |
Case reports of seizures made worse |
PENNYROYAL |
Several case reports of seizures due to suspected substance monoterpine R-(plus)-pulegone |
SAGE (essential oil) + # $ |
Due to substance thujone |
SHANKHAPUSHPI |
Reported in combination with phenytoin |
STAR ANISE (Japanese) |
Several case reports |
STAR FRUIT |
Some case reports |
WORMWOOD |
Due to substance thujone |
Table 7: Herbal-Drug Interactions
BETA-CAROTENE * |
May have slight effects on CYP enzymes |
FOLIC ACID + & |
High doses may induce metabolism of phenytoin |
GINKO BILOBA+ # |
Induces CYP2C19 metabolism of drugs. |
GOLDENSEAL |
Inhibits metabolism of drugs by CYP2D6 and CYP3A4/5 |
GRAPEFRUIT JUICE |
Inhibits CYP3A4 activity in the GI tract. Increase plasma concentrations of drugs that undergo significant GI metabolism by CYP3A4. |
GROUNDSEL * |
Induces CYP enzymes. Use with enzyme inducers increases risk of toxicity. |
INDIAN LONG PEPPER * |
Effects on increased absorption and elimination of drugs (e.g. phenytoin) via active compound piperin. May affect other AEDs as well. |
KAVA |
Inhibits metabolism of drugs by CYP2E1 only |
NICOTINAMIDE |
Inhibits conversion of primidone to phenobarbital. Inhibits the metabolism of carbamazepine resulting in increased concentrations |
Bai Shao |
Alters carbamazepine and phenytoin concentrations by affecting absorption. Carbamazepine concentrations may increase. Phenytoin absorption may be delayed. |
SHANKHAPUSHI |
Reported to decrease serum phenytoin levels (shown in rats) |
SHO-SEIRU-TO |
May affect AED levels (e.g. carbamazepine) by altering gastric transit times. |
ST. JOHN’S WORT $ |
Induces CYP3A4, CYP2C19 and CYP2E1 and p-glycoprotein and decreases the concentration of many drugs including oral contraceptives. Responsible for the most clinically significant herbal drug interactions |
Major CYP enzymes involved in AED metabolism
CYP2C9 phenytoin (major), valproate(major), phenobarbital (secondary)
CYP2C19 phenobarbital (major), phenytoin (secondary)
CYP3A4 carbamazepine (major), ethusuximide (major), felbamate (major)
CYP2C8 carbamazepine (secondary)
CYP2A6 valproic (secondary)
CYP2E1 felbamate
General References:
Natural Medicine Database Reference (www.naturaldatabase.com)
A good resource for quickly checking on various herbal preparations (including brand name products with multiple ingredients). There are some products missing in the database. Epilepsy related coverage lacks depth of the other reviews (below).
Spinella M HERBAL MEDICINES AND EPILEPSY: THE POTENTIAL FOR BENEFIT AND ADVERSE EFFECTS Epilepsy & Behavior(2001)2, 524–532
A good review on interaction of some of the most common herbal remedies with epilepsy.
Schachter S C COMPLEMENTARY AND ALTERNATIVE MEDICAL THERAPIES Current Opinion in Neurology (2008) 21:184–189
A broad overview of various CAM therapies used in epilepsy. Good refrences on what is traditionally used.
Tyagi A and N Delanty HERBAL REMEDIES, DIETARY SUPPLEMENTS, AND SEIZURES Epilepsia (2003) 44(2):228–235
Another good review. Emphasizes toxicity and risks of various herbal remedies when it comes to epilepsy
Samuels N et al HERBAL MEDICINE AND EPILEPSY: PROCONVULSIVE EFFECTS AND INTERACTIONS WITH ANTIEPILEPTIC DRUGS Epilepsia (2008): 49(3):373–380
A very up-to-date review of potential risks of herbal remedies in epilepsy
Asadi-Pooya A A et al. NUTRITIONAL SUPPLEMENTS, FOODS, AND EPILEPSY: IS THERE A RELATIONSHIP? Epilepsia (2008) 49(11):1819–1827
A good review of nutritional supplements (emphais is on food and other supplements as opposed to herbs) with evaluation of benefits, seizure risks and risk of drug interactions.
Numbered References From Text
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2. Hoon Chul Kang et al. EARLY- AND LATE-ONSET COMPLICATIONS OF THE KETOGENIC DIET FOR INTRACTABLE EPILEPSY Epilepsia 2004; 45(9):1116–1123
3. Eric H. Kossoff et al. A MODIFIED ATKINS DIET IS EFFECTIVE FOR THE TREATMENT OF INTRACTABLE PEDIATRIC EPILEPSY Epilepsia 2006; 47(2):421–424
4. Ramaratnam S et al PSYCHOLOGICAL TREATMENTS FOR EPILEPSY. Cochrane Database Syst Rev 2005; 4:CD002029
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6. Cheuk DK, Wong V. ACUPUNCTURE FOR EPILEPSY. Cochrane Database Syst Rev 2006; (2):CD005062
7. Sterman MB. BASIC CONCEPTS AND CLINICAL FINDINGS IN THE TREATMENT OF SEIZURE DISORDERS WITH EEG OPERANT CONDITIONING. Clin Electroencephalogr 2000; 31:45-55
8. Natural Medicine Database (www.naturaldatabase.com)
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10.El Yacoubi M et al. EVIDENCE FOR THE INVOLVEMENT OF THE ADENOSINE A(2A) RECEPTOR IN THE LOWERED SUSCEPTIBILITY TO PENTYLENETETRAZOL-INDUCED SEIZURES PRODUCED IN MICE BY LONG-TERM TREATMENT WITH CAFFEINE. Neuropharmacology 2008; 55(1):35-40
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