Antiepileptic drugs utilized for seizure disorders, migraine, neuropathic pain, chronic pain processes and psychiatric disorders.
The goal of therapy with anti-seizure drugs is to achieve complete seizure remission without adverse event.
Patients with generalized epilepsy amor likely to become seizure free, 64-82%, than those with focal epilepsy at 25 to 70%.
Recurrent seizures are associated with seizure related injuries in approximately 28 to 40% of patients and the mortality rate that is 1.6 to 9.3 times higher than the general population during the first two years of after diagnosis.
Currently 20 medications approved in the US for seizures.
Diverse class of medications that reduce neuronal excitability, prevent seizures, and act on a range of molecular targets including sodium channels and the glutamate and gamma-aminobutyric acid (GABA) systems.
Antiepileptic drugs are divided into narrow spectrum and broad spectrum agents.
Narrow spectrum antiepileptic drugs only work for specific types of seizures and may be ineffective or worsen other types of seizures:carbamazepine, oxcarbazepine, gabapentin, pregabalin.
Narrow spectrum antiepileptic drugs can exacerbate myoclomic and absence seizures.
Broad-spectrum antiepileptic drugs have efficacy for a wide range of seizures including focal, absence, generalized tonic clonic and myoclonic.
Newer antiepileptic drugs have fewer side effects than older agents.
Potential side effects of all antiepileptic drugs include: fatigue, gastrointestinal side effects, mood changes, and cognitive side effects.
Older anti-epileptic drugs are associated with increased rates of fracture due to osteopenia.
Bone density screen is recommended with the use of: phenytoin, phenobarbital, primidone, valproate, carbamazine.
Accurate identification of the seizure type in epilepsy syndrome is important for selecting the appropriate anti-seizure drug.
Effective treatment for all types of neuropathic pain.
Most anti-epileptic drugs are efficacious in the treatment of focal epilepsy, but fewer are effective for generalized epilepsy.
Carbamazine and phenytoin are the most effective for focal epilepsy followed by valproic acid.
Valproic acid is the most effective drug for idiopathic generalized epilepsy syndromes.
Metaaanalyses shows that there is no significant differences in efficacy and adverse effects in multiple drugs including carbamazine, levetiracetam, zonisamide, lacosamide, and elsicarbezine.
Useful as prophylaxis for seizures, chronic pain syndromes, bipolar and other mood disorders and alcohol dependence disorders.
A number of drugs used for epilepsy treatment have apparent analgesic properties through their effects of lowering neurotransmitter release or reducing neuronal firing.
Anti-seizure drug therapy should be started as mono therapy and a low-dose with the stepwise titration to attain an initial moderate those that minimizes adverse effects.
If seizures recur, doses are increased until there’s no subsequent seizures, the maximum dose is reached, or adverse events occur, which ever happens first.
If persistent seizures occur at optimal doses or there are adverse events and alternative antiseizure drug is added until adequate dose is reached: at that point the first anti-seizure drug can be tapered to lower doses until it is discontinued.
Intravenous loading is considered when rapid attainment of therapeutic serum concentrations of an anti-seizure drug is necessary, such as with focal or generalized seizures occurring in clusters.
Treatment with more than one drug is typically considered with treatment resistant epilepsy defined as the persistent epilepsy after a trial with two appropriate anti-seizure drugs at optimal doses.
Folate supplementation is recommended for all women of childbearing age taking any antiepileptic drug.
Associated with osteopenia and osteoporosis.
Not associated with abuse.
Typically the dose of single drug is adjusted to reach maximally tolerated levels or until the patients is seizure free.
Initiating anti-seizure medication immediately after a first seizure can reduce the chances of having another one by more than one third within the next two years.
Seizure medicines carry risk of adverse events that ranges from 7-31% and include: nausea, blurred vision, and dizziness.
If patients continue to have seizures when maximum dose is reached a second drug can be added and the first drug tapered off or it can be added the first drug if it was partially successful.
Rare reactions to seizure medicines include serious allergic reactions, blood disorders, and liver problems.
Patients taking anticonvulsants have approximately twice the risk of suicidal ideation or behavior compared with placebo (FDA).
P
The use of gabapentin, lamotrigine, oxcarbazine, and tiagabine compared with topiramate may be associated with increased risk of suicidal acts or violent deaths (Patorno E)
All anti-seizure medications are potential teratogens, and could cause congenital malformations and congenital or behavioral impairments.
Can cause major malformations, microcephaly, growth retardation, and abnormalities of the face and fingers in infants exposed to them during pregnancy.
Lamotrigine and Levetiracetam are associated with the lowest rates of congenital malformations comparable to those with healthy women receiving no medication.
Valproic acid has the highest risk of teratogenic effects, up to 11%, which are dose dependent, and include CNS, cardiac, urologic, and facial malformations.
Fetal exposure to Topiramate and is associated with an increased risk of autism spectrum disorder,
All anti-seizure medications interact with sodium or calcium channels, or both, and can cause EKG abnormalities.
Studies have shown 7.7-12% of nursing home patients with falls were taking first generation antiepileptic drugs and 42% using the drugs for non seizure conditions.
First generation antiepileptic drugs include carbamazine, phenytoin and valproic acid.
Phenytoin, carbamazine, gabapentin,vigabatrin, tiagabine, and pregabalin may worsen absence epilepsy and myoclonic seizures.
Lamotrigine can exacerbate some myoclonic epilepsy syndromes.
Treatment resistant epilepsy associated with anxiety, depression, cognitive and memory disturbances.
Pseudo resistance results from the use of wrong anticonvulsants for the type of seizure and epilepsy or paroxysmal epileptic seizures due to some psychiatric disorders., some sleep disorders, migraines and migraine equivalents, TIAs, movement disorders and syncopal episodes:approximately one of every 4 to 5 patients referred to an epilepsy center with a diagnosis of treatment resistant epilepsy does not have epilepsy.
Treatment of resistant epilepsy alternatives include surgery, neuromodulation therapies such as vagal nerve stimulation and deep brain stimulation, ketogenic diet and the exclude the possibility of pseudo resistance.
Useful adjuncts for the treatment of alcohol withdrawal, but do not fully replace benzodiazepines, which remain the treatment of choice.
Anti-epileptic drug selection requires an understanding of the patients epilepsy and consideration of comorbidities and potential for adverse events.
Patients are considered medically refractory if they had failed at least two appropriate antiepileptic drugs.
First generation anticonvulsant increase the risk of bone loss, imbalance and risk of falls and fractures.
Exposure to anti-seizure drugs is associated with increased risk of cardiovascular disease, perhaps mediated in part by adverse effects on lipids, C reactive protein, and homocysteine.
Second generation antiepileptic drugs include felbamate, gabapentin, topiramate, oxycarbazepine, lamotrigine, levetiracetam, pregabalin, and zonisamide.
Second generation antiepileptic medications felt to be better tolerated and safer than first generation drugs.
Most second generation drugs are associated with a dose dependent risk of imbalance and ataxia, with the exception of gabapentin and levetiracetam.
Levetiracetam, topiramate, and vigabatrin anticonvulsant drugs exhibit linear kinetics.
Carbamazine, phenytoin, gabapentin, and valproic acid are anticonvulsant drugs with nonlinear kinetics.
Gabapentin and pre-Gabalin are ligands of the alpha2 delta subunit of neuronal voltage-gauge calcium channels, causing reduced calcium dependent release of excitatory neurotransmitters, thereby decreasing neuronal excitability.
Asian patients who receive phenytoin, fosphenytoin or carbamazine are at higher risk for development of skin reactions including Steven-Johnson syndrome or toxic dermal necrolysis.Individuals carrying HLA-B 1502 allele of the human leukocyte antigen gene, more common in Asians, may be more likely to develop severe skin reactions to such agents.
Useful in treating alcohol dependence.
About 3 to 60% of patients with epilepsy develop a drug hypersensitivity to anti-seizure drugs.
There is a five fold increase in the risk of anti-seizure drug associated rash.
Stevens-Johnson syndrome and or toxic epidermal necrosis occurs in 1 to 8 new cases per 10,000 new anti-seizure drug users.
TREATMENT:
Whether to prescribe anti-seizure medications after a first epileptic seizure depends whether the seizure is acute, symptomatic, or unprovoked.
Acute symptomatic seizures related to acute this stroke, toxic stimuli such as alcohol withdrawal or cocaine, or metabolic disorders of hyponatremia, hypoglycemia/hyperglycemia can be treated for the underlying condition, which is sufficient to minimize seizure recurrence.
The risk of seizure recurrence is lower for patients with provoked seizures than for patients with spontaneous seizures at 10 year follow-up.
In some strokes that seizures occur within the first seven days, will not require long-term therapy for seizures.
Seizures that are related to strokes beyond one week will be treated with long-term anti seizure therapy.
Discontinuing anti-seizure drugs is considered after a seizure free period of at least two years.
Even after two years the recurrence rate can be approximately 30 to 50%.
The risk of seizure recurrence is highest in the first 6 to 12 months after anticonvulsant agents are discontinued and decreases after the second year.
Slower tapering of anti-convulsion drugs over six months is considered for carbamazepine, barbiturates, and benzodiazepines, because they may be associated with withdrawal seizures.
Factors associated with seizure recurrence include a shorter period without a seizure, a history of focal epilepsy, EEG findings with eliptoform discharges, a history of myoclonic seizures, or multiple seizure types, poor initial response to treatment, family, history of epilepsy, mesial, temporal, sclerosis, and old age at the onset of epilepsy.
Treatment resistant is defined as persistent seizures after two trials with an appropriate anti-seizure medication at optimal doses, administered a single or multiple drug therapy.
Drug resistant epilepsy occurs in approximately 30 to 40% of all patients with epilepsy, but is more frequent in focal than generalized disease.