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Treatment of patients with absence seizures only is mainly with valproic acid or ethosuximide, which are of equal efficacy controlling absences in around 75% of patients. Lamotrigine monotherapy is less effective, with nearly half of the patients becoming seizure free. This view has been recently confirmed by Glauser et al. (2010), who studied the effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug dosages were incrementally increased until the child was free of seizures, the maximal allowable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar and were higher than the rate for lamotrigine. There were no significant differences between the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide.
If monotherapy fails or unacceptable adverse reactions appear, replacement of one by another of the three antiepileptic drugs is the alternative. Adding small doses of lamotrigine to sodium valproate may be the best combination in resistant cases.
While ethosuximide is effective in treating only absence seizures, valproic acid is effective in treating multiple seizure types including tonic-clonic seizure and partial seizure, as such it may be a better choice if a patient is exhibiting multiple types of seizures.
Similarly, lamotrigine treats multiple seizure types including partial seizures and generalized seizures, therefore it is also an option for patients with multiple seizure types. Clonazepam (Klonopin, Rivotril) is effective in the short term but is not generally recommended for treatment of absence seizure because of the rapid development of tolerance and high frequency of side effects.
Carbamazepine, vigabatrin, and tiagabine are contraindicated in the treatment of absence seizures, irrespective of cause and severity. This is based on clinical and experimental evidence. In particular, the GABA agonists vigabatrin and tiagabine are used to induce, not to treat, absence seizures and absence status epilepticus. Similarly, oxcarbazepine, phenytoin, phenobarbital, gabapentin, and pregabalin should not be used in the treatment of absence seizures because these medications may worsen absence seizures.
The trigger needs to be identified before prescribing anti-epileptics. The most commonly prescribed drugs for reflex epilepsy are valproate, carbamazepine and clonazepam, though lamotrigine, levetiracetam are promising.
Seven anti-epileptic drugs are approved for use in cases of suspected primary generalized epilepsy:
- Felbamate
- Levetiracetam
- Zonisamide
- Topiramate
- Valproate
- Lamotrigine
- Perampanel
Valproate, a relatively old drug, is often considered the first-line treatment. It is highly effective, but its association with fetal malformations when taken in pregnancy limits its use in young women.
All anti-epileptic drugs (including the above) can be used in cases of partial seizures.
The first line treatment of choice for someone who is actively seizing is a benzodiazepine, most guidelines recommend lorazepam. This may be repeated if there is no effect after 10 minutes. If there is no effect after two doses, barbiturates or propofol may be used. Benzodiazepines given by a non-intravenous route appear to be better than those given by intravenous as the intravenous takes time to start.
Ongoing anti-epileptic medications are not typically recommended after a first seizure except in those with structural lesions in the brain. They are generally recommended after a second one has occurred. Approximately 70% of people can obtain full control with continuous use of medication. Typically one type of anticonvulsant is preferred. Following a first seizure, while immediate treatment with an anti-seizure drug lowers the probability of seizure recurrence up to five years it does not change the risk of death and there are potential side effects.
In seizures related to toxins, up to two doses of benzodiazepines should be used. If this is not effective pyridoxine is recommended. Phenytoin should generally not be used.
There is a lack of evidence for preventative anti-epileptic medications in the management of seizures related to intracranial venous thrombosis.
Based on anecdotal evidence, the drugs of choice are those used for other idiopathic generalized epilepsies. Valproate alone, or most probably in combination with clonazepam, levetiracetam, lamotrigine or ethosuximide, appears to be the most effective regimen. The choice of the second drug depends on the main seizure type. Clonazepam is highly efficacious in eyelid myoclonia and myoclonic jerks. Of the newer antiepileptic drugs, levetiracetam may be the most effective, because of its anti myoclonic and anti photosensitive properties. Lamotrigine is very effective in absence seizures but may exaggerate myoclonic jerks.
Contra-indicated drugs are: Carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin, tiagabine and vigabatrin.
Lifestyle and avoidance of seizure precipitants are important. Non-pharmacological treatments used for photosensitive patients (such as wearing special glasses or the newly commercially available blue Z1 lenses) should be employed in Jeavons syndrome when photosensitivity persists.
Many antiepileptic drugs are used for the management of canine epilepsy. Oral phenobarbital, in particular, and imepitoin are considered to be the most effective antiepileptic drugs and usually used as ‘first line’ treatment. Other anti-epileptics such as zonisamide, primidone, gabapentin, pregabalin, sodium valproate, felbamate and topiramate may also be effective and used in various combinations. A crucial part of the treatment of pets with epilepsy is owner education to ensure compliance and successful management.
Avoidance therapy consists of minimizing or eliminating triggers. For example, in those who are sensitive to light, using a small television, avoiding video games, or wearing dark glasses may be useful. Operant-based biofeedback based on the EEG waves has some support in those who do not respond to medications. Psychological methods should not, however, be used to replace medications. Some dogs, commonly referred to as seizure dogs, may help during or after a seizure. It is not clear if dogs have the ability to predict seizures before they occur.
The mainstay treatment of epilepsy is anticonvulsant medications, possibly for the person's entire life. The choice of anticonvulsant is based on seizure type, epilepsy syndrome, other medications used, other health problems, and the person's age and lifestyle. A single medication is recommended initially; if this is not effective, switching to a single other medication is recommended. Two medications at once is recommended only if a single medication does not work. In about half, the first agent is effective; a second single agent helps in about 13% and a third or two agents at the same time may help an additional 4%. About 30% of people continue to have seizures despite anticonvulsant treatment.
There are a number of medications available including phenytoin, carbamazepine and valproate. Low-quality evidence suggests that phenytoin, carbamazepine, and valproate may be equally effective in both focal and generalized seizures. Controlled release carbamazepine appears to work as well as immediate release carbamazepine, and may have fewer side effects. In the United Kingdom, carbamazepine or lamotrigine are recommended as first-line treatment for focal seizures, with levetiracetam and valproate as second-line due to issues of cost and side effects. Valproate is recommended first-line for generalized seizures with lamotrigine being second-line. In those with absence seizures, ethosuximide or valproate are recommended; valproate is particularly effective in myoclonic seizures and tonic or atonic seizures. If seizures are well-controlled on a particular treatment, it is not usually necessary to routinely check the medication levels in the blood.
The least expensive anticonvulsant is phenobarbital at around $5 USD a year. The World Health Organization gives it a first-line recommendation in the developing world and it is commonly used there. Access however may be difficult as some countries label it as a controlled drug.
Adverse effects from medications are reported in 10 to 90% of people, depending on how and from whom the data is collected. Most adverse effects are dose-related and mild. Some examples include mood changes, sleepiness, or an unsteadiness in gait. Certain medications have side effects that are not related to dose such as rashes, liver toxicity, or suppression of the bone marrow. Up to a quarter of people stop treatment due to adverse effects. Some medications are associated with birth defects when used in pregnancy. Many of the common used medications, such as valproate, phenytoin, carbamazepine, phenobarbitol, and gabapentin have been reported to cause increased risk of birth defects, especially when used during the first trimester. Despite this, treatment is often continued once effective, because the risk of untreated epilepsy is believed to be greater than the risk of the medications. Among the antiepileptic medications, levetiracetam and lamotrigine seem to carry the lowest risk of causing birth defects.
Slowly stopping medications may be reasonable in some people who do not have a seizure for two to four years; however, around a third of people have a recurrence, most often during the first six months. Stopping is possible in about 70% of children and 60% of adults.
Valproate is available to be given intravenously, and may be used for status epilepticus. Carbamazepine is not available in an intravenous formulation, and does not play a role in status epilepticus.
Phenytoin was once another first-line therapy, although the prodrug fosphenytoin can be administered three times as fast and with far fewer injection site reactions. If these or any other hydantoin derivatives are used, then cardiac monitoring is a must if they are administered intravenously. Because the hydantoins take 15–30 minutes to work, a benzodiazepine or barbiturate is often coadministered. Because of diazepam's short duration of action, they were often administered together anyway.
Like other forms of epilepsy, nocturnal epilepsy can be treated with anti-convulsants.
Despite the effectiveness of anti-convulsants in people who suffer from nocturnal epilepsy, the drugs are shown to disrupt a person's sleeping structure. This may cause concern in people who suffer specifically from nocturnal epilepsy because undisrupted sleep is important for these people, as it lowers the likeliness of epileptic symptoms to arise.
One particular study by V. Bradley and D. O'Neill analysed the different forms of epilepsy, including nocturnal epilepsy and its relationship with sleep. They found that some patients only experienced epileptic symptoms while they are asleep (nocturnal epilepsy), and that maintaining good sleep helped in reducing epileptic symptoms. Another study determined that anti-convulsant medications can minimize epilepsy not just in people who are awake, but also in people who are asleep. However, some of these anti-convulsant medications did also have adverse effects on subjects' sleeping structures, which can exacerbate epileptic symptoms in people who suffer from nocturnal epilepsy.
To minimize epileptic seizures in these people, it is important to find an anti-convulsant medication that does not disrupt a person's sleeping structure. The anti-convulsant medications that were tested to meet this criteria are: phenobarbital, phenytoin, carbamazepine, valproate, ethosuximide, felbamate, gabapentin, lamotrigine, topiramate, vigabatrin, tiagabine, levetiracetam, zonisamide, and oxcarbazepine. Oxcarbazepine is shown to have the least amount of adverse effects on sleep. Another study shows that it enhances slow wave-sleep and sleep continuity in patients with epilepsy.
Lorazepam and clonazepam are front line treatment for severe convulsions, belonging to the benzodiazepine class of medications.
Patients with ICOE-G need prophylactic treatment mainly with carbamazepine or other antiepileptic drugs licensed for focal seizures. A slow reduction in the dose of medication 2 or 3 years after the last visual or other minor or major seizure should be advised, but if visual seizures reappear, treatment should be restored.
Helmets may be used to provide protection to the head during a seizure. Some claim that seizure response dogs, a form of service dog, can predict seizures. Evidence for this, however, is poor. At present there is not enough evidence to support the use of cannabis for the management of seizures, although this is an ongoing area of research. There is tentative evidence that a ketogenic diet may help in those who have epilepsy and is reasonable in those who do not improve following typical treatments.
Anticonvulsants are the most successful medication in reducing and preventing seizures from reoccurring. The goal of these medications in being able to reduce the reoccurrence of seizures is to be able to limit the amount of rapid and extensive firing of neurons so that a focal region of neurons cannot become over-activated thereby initiating a seizure. Although anticonvulsants are able to reduce the amount of seizures that occur in the brain, no medication has been discovered to date that is able to prevent the development of epilepsy following a head injury. There are a wide range of anticonvulsants that have both different modes of action and different abilities in preventing certain types of seizures. Some of the anticonvulsants that are prescribed to patients today include: Carbamazepine (Tegretol), Phenytoin (Dilantin Kapseals), Gabapentin (Neurontin), Levetiracetam (Keppra), Lamotrigine (Lamictal), Topiramate (Topamax), Tiagabine (Gabitril), Zonisamide (Zonegran) and Pregabalin (Lyrica).
Given the benign nature of the condition and the low seizure frequency, treatment is often unnecessary. If treatment is warranted or preferred by the child and his or her family, antiepileptic drugs can usually control the seizures easily. Carbamazepine is the most frequently used first-line drug, but many other antiepileptic drugs, including valproate, phenytoin, gabapentin, levetiracetam and sultiame have been found effective as well. Bedtime dosing is advised by some. Treatment can be short and drugs can almost certainly be discontinued after two years without seizures and with normal EEG findings, perhaps even earlier.
Parental education about Rolandic epilepsy is the cornerstone of correct management. The traumatizing, sometimes long-lasting effect on parents is significant.
It is unclear if there are any benefits to clobazam over other seizure medications.
Seizures in Dravet syndrome can be difficult to manage but may be reduced by anticonvulsant medications such as clobazam, stiripentol, topiramate and valproate. Because the course of the disorder varies from individual to individual, treatment protocols may vary. A diet high in fats and low in carbohydrates may also be beneficial, known as a ketogenic diet. Although diet adjustment can help, it does not eliminate the symptoms. Until a better form of treatment or cure is discovered, those with this disease will have myoclonic epilepsy for the rest of their lives.
Certain anticonvulsant drugs that are classed as Sodium Channel Blockers are now known to make seizures worse in most Dravet patients. These drugs include carbamazepine, gabapentin, lamotrigine, and phenytoin.
Treatments include cognitive rehabilitation through psychomotor and speech therapy. In addition, valproate is often administered to prevent recurrence of febrile seizures and benzodiazapine is used for long lasting seizures, but these treatments are usually insufficient.
Stiripentol was the only drug for which a double-blind placebo trial was performed and this drug showed efficacy in trials. It acts as a GABAergic agent and as a positive allosteric modulator of GABA receptor. Stiripentol, can improve focal refractory epilepsy, as well as Dravet's syndrome, supplemented with clobazam and valproate was approved in Europe in 2007 as a therapy for Dravet syndrome and has been found to reduce overall seizure rate by 70%. In cases with more drug resistant seizures, topiramate and the ketogenic diet are used as alternative treatments.
Cannabidiol (CBD) has received orphan drug status in the United States, for treatment of Dravet syndrome which will allow it to be studied.
Like other forms of epilepsy, abdominal epilepsy is treated with anticonvulsant drugs, such as phenytoin. Since no controlled studies exist, however, other drugs may be equally effective.
The lack of generally recognized clinical recommendations available are a reflection of the dearth of data on the effectiveness of any particular clinical strategy, but on the basis of present evidence, the following may be relevant:
- Epileptic seizure control with the appropriate use of medication and lifestyle counseling is the focus of prevention.
- Reduction of stress, participation in physical exercises, and night supervision might minimize the risk of SUDEP.
- Knowledge of how to perform the appropriate first-aid responses to seizure by persons who live with epileptic people may prevent death.
- People associated with arrhythmias during seizures should be submitted to extensive cardiac investigation with a view to determining the indication for on-demand cardiac pacing.
- Successful epilepsy surgery may reduce the risk of SUDEP, but this depends on the outcome in terms of seizure control.
- The use of anti suffocation pillows have been advocated by some practitioners to improve respiration while sleeping, but their effectiveness remain unproven because experimental studies are lacking.
- Providing information to individuals and relatives about SUDEP is beneficial.
Most children who develop epilepsy are treated conventionally with anticonvulsants. In about 70% of cases of childhood epilepsy, medication can completely control seizures. Unfortunately, medications come with an extensive list of side effects that range from mild discomfort to major cognitive impairment. Usually, the adverse cognitive effects are ablated following dose reduction or cessation of the drug.
Medicating a child is not always easy. Many pills are made only to be swallowed, which can be difficult for a child. For some medications, chewable versions do exist.
The ketogenic diet is used to treat children who have not responded successfully to other treatments. This diet is low in carbohydrates, adequate in protein and high in fat. It has proven successful in two thirds of epilepsy cases.
In some cases, severe epilepsy is treated with the hemispherectomy, a drastic surgical procedure in which part or all of one of the hemispheres of the brain is removed.
The prognosis of ICOE-G is unclear, although available data indicate that remission occurs in 50–60% of patients within 2–4 years of onset. Seizures show a dramatically good response to carbamazepine in more than 90% of patients. However, 40–50% of patients may continue to have visual seizures and infrequent secondarily generalized convulsions, particularly if they have not been appropriately treated with antiepileptic drugs.
Jeavons syndrome is a lifelong disorder, even if seizures are well controlled with antiepileptic drugs. Men have a better prognosis than women. There is a tendency for photosensitivity to disappear in middle age, but eyelid myoclonia persists. It is highly resistant to treatment and occurs many times a day, often without apparent absences and even without demonstrable photosensitivity.
Concerning more serious afflictions, the complex origins of myoclonus may be treated with multiple drugs, which have a limited effect individually, but greater when combined with others that act on different brain pathways or mechanisms. Treatment is most effective when the underlying cause is known, and can be treated as such. Some drugs being studied in different combinations include clonazepam, sodium valproate, piracetam, and primidone. Hormonal therapy may improve responses to antimyoclonic drugs in some people.
Some studies have shown that doses of 5-hydroxytryptophan (5-HTP) leads to improvement in patients with some types of action myoclonus and PME. These differences in the effect of 5-HTP on patients with myoclonus have not yet been explained.
Many of the drugs used for myoclonus, such as barbiturates, phenytoin and primidone, are also used to treat epilepsy. Barbiturates slow down the central nervous system and cause tranquilizing or antiseizure effects. Phenytoin and primidone are effective antiepileptics drugs, although phenytoin can cause liver failure or have other harmful long-term effects in patients with PME. Sodium valproate is an alternative therapy for myoclonus and can be used either alone or in combination with clonazepam. Some people have adverse reactions to clonazepam and/or sodium valproate.
When patients are taking multiple medications, the discontinuation of drugs suspected of causing myoclonus and treatment of metabolic derangements may resolve some cases of myoclonus. When pharmacological treatment is indicated anticonvulsants are the main line of treatment. Paradoxical reactions to treatment are notable. Drugs which most people respond to may in other individuals worsen their symptoms. Sometimes this leads to the mistake of increasing the dose, rather than decreasing or stopping the drug. Treatment of myoclonus focuses on medications that may help reduce symptoms. Drugs used include sodium valproate, clonazepam, the anticonvulsant levetiracetam, and piracetam. Dosages of clonazepam usually are increased gradually until the patient improves or side effects become harmful. Drowsiness and loss of coordination are common side effects. The beneficial effects of clonazepam may diminish over time if the patient develops a tolerance to the drug.
In forms of myoclonus where only a single area is affected, and even in a few other various forms, Botox injections (OnabotulinumtoxinA) may be helpful. The chemical messenger responsible for triggering the involuntary muscle contractions is blocked by the Botulinum toxins of the Botox.
Surgery is also a viable option for treatment if the symptoms are caused by a tumor or lesion in the brain or spinal cord. Surgery may also correct symptoms in those where myoclonus affects parts of the face or ear. While DBS is still being studied for use with myoclonus, Deep Brain Stimulation has also been tried in those with this and other movement disorders.
Most generalized epilepsy starts during childhood. While some patients outgrow their epilepsy during adolescence and no longer need medication, in others, the condition remains for life, thereby requiring lifelong medication and monitoring.