eMedicine Specialties > Neurology > Seizures and Epilepsy
Epilepsy in Children with Mental Retardation: Treatment & Medication
Updated: Aug 29, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Seizure disorders are generally more severe in people with mental retardation. The basic treatment principles of epileptic disorders also apply to patients with mental retardation. There are several options for the long-term treatment of epileptic seizures, including antiseizure medications, vagal nerve stimulation, ketogenic diet, and surgery. These options are not mutually exclusive and should be used concurrently in the same individual if needed.
Monotherapy is ideal, and polytherapy should be used only when no other options are available. Starting the treatment with one medication in small doses and increasing in increments weekly or biweekly is the preferred method. Most of the side effects are seen when the full dose of medication is achieved in a short period of time. Titration periods of 4-6 weeks are usually safe in terms of preventing side effects. The only inconvenience is the possibility of a seizure during the titration period; however, in the long-term, whenever possible, start with a low dose and increase the medication slowly.
It is not unusual for people with a first seizure to be seen in the emergency department and be sent home with a full dose of medication. These individuals are more prone to have side effects a few days after the initiation of the therapy. In these cases, the medication should be decreased or even stopped and then restarted later when the signs of intoxication have subsided. Unfortunately, in many instances this is seen as intolerance to the medications or an allergy, which is not the case. Medications that are potentially useful should not be excluded due to side effects that could have been avoided with a slow titration.
In many instances, discontinuing antiepileptic medications is possible after a seizure-free period. The time varies among physicians, but discontinuing medications after 2 years without seizures is usually considered safe. However, in the author's practice, medications may be safely discontinued after 4-5 years without seizures in persons with brain damage. Discontinue antiepileptic medications slowly. In children treated with multiple medications, the author recommends tapering one medication at a time, allowing approximately 6-12 months to discontinue each medication. Withdrawal seizures are not unusual and are not necessarily an indication that the medication being tapered is needed. However, in most instances delaying the tapering of the medications is safer.
Many individuals with brain damage present with paradoxical reactions to medications. Sedation, a common side effect of these medications, is more obvious when the medications are used at maximal dose from the beginning of the therapy. Behavior deterioration or the emergence of new abnormal behaviors can be the result of the use of antiepileptic medications.
In 60-70% of persons without mental retardation, seizures are controlled with the available antiepileptic medications either alone or in combination. In children with mental retardation, the success rate is much lower, around 50% or less in certain subgroups, eg, children with the Lenox-Gastaut syndrome.
Establishing that the patient has epileptic seizures is essential before the initiation of treatment. One of the most serious pitfalls in the treatment of recurrent epileptic seizures is failure to differentiate them from nonepileptic events. Nonepileptic events are a confounding factor in persons with and without mental retardation. The lack of recognition leads to unnecessary treatment in addition to the complications of missing the right diagnosis (eg, syncope, migraine, cardiac arrhythmias, vestibular disorders, sleep disturbances).
Reaching the correct diagnosis requires obtaining an accurate history of the event, performing physical and neurologic examinations, obtaining EEG (including EEG-video monitoring or some form of long-term monitoring if there is any doubt about the diagnosis), and conducting neuroradiologic evaluation in any case of new-onset seizure. Once the diagnosis of epileptic seizure is established, the next step is to determine the type of seizure and if possible the epileptic syndrome. Even though some of the antiepileptic medications are effective in many different types of seizures, some are more useful in certain syndromes. For example, valproic acid, lamotrigine, and topiramate are effective in the Lennox-Gastaut syndrome, while carbamazepine would be a poor choice in this syndrome.
- The mainstay of medical care is the use of antiseizure medications.
- Until 1993, only a limited number of antiepileptic medications was available to choose from if practicing in the United States. These are recognized today as the old drugs (ie, phenobarbital, primidone, carbamazepine, valproic acid, ethosuximide, acetazolamide, several benzodiazepines such as diazepam, clonazepam, and Tranxene).
- In the last decade, several antiepileptic medications have been approved in United States; the new drugs include felbamate, gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine, and zonisamide.
- Other therapeutic options have not been approved in United States but are available in other countries; these include vigabatrin, sulthiame, and clobazam.
- The majority of the new antiseizure drugs recently introduced in United States were approved after studies conducted mostly in persons with intractable seizures of the partial or focal type. In most instances, these medications were used as add-on medications. Few of the new antiepileptic drugs have been evaluated in monotherapy trials. Very few studies have compared these medications with each other.
- Few studies evaluate these medications in children; however, the pathophysiology of partial seizures in children is similar to the pathophysiology of seizures in adults. Furthermore, each antiseizure medication tested as adjunctive therapy in children older than 2 years with refractory partial seizures has demonstrated the same efficacy as in adults. Although not the ideal situation, studies in adults can indicate efficacy in children.
- A meta-analysis of randomized controlled trials involving some of the new medications (ie, gabapentin, lamotrigine, topiramate, zonisamide, tiagabine, vigabatrin) showed than when compared with placebo there was no conclusive evidence for a difference in efficacy or tolerability among the drugs.
- Even though more information is needed about these new drugs, some evidence suggests that there are advantages with these new agents.
- Lamotrigine, topiramate, and zonisamide have broad-spectrum activity and are effective in the treatment of generalized seizures, besides being effective in local-onset seizures. These drugs might help in the treatment of the Lenox-Gastaut syndrome.
- Gabapentin, lamotrigine, and oxcarbazepine are as effective as carbamazepine in individuals with partial-onset seizures but with fewer side effects.
- Unlike the old drugs, most of the new antiepileptic drugs do not induce hepatic enzymes. Consequently, the interaction with other drugs is decreased or eliminated. Most of the old drugs enhance the metabolism of oral contraceptives, which might result in unexpected pregnancies. With the exception of felbamate, oxcarbazepine, and topiramate, the new drugs do not interfere with oral contraceptives.
- The incidence of congenital malformations in the offspring of women with epilepsy is 4-6%, twice that of the general population. Phenobarbital, phenytoin, carbamazepine, and valproic acid are proven teratogenics and should be avoided during pregnancy, mostly in the first trimester. The teratogenic effects are increased with polypharmacy. The teratogenic mechanism is not known but is probably related to folate deficiency. Folate supplementation is recommended in women of childbearing age taking antiepileptic medication.
- The North American Antiepileptic Drug Pregnancy Registry tracks the incidence of malformations in women with epilepsy taking medication during pregnancy. Data showed that major birth defects were found in 8.8% of the participants on valproic acid, in 6.3% of participants on phenobarbital, and in 1.6% of the control group.
- The Lamotrigine Pregnancy Registry, which collects information on women exposed to lamotrigine in the first trimester, found an incidence of major birth defects of 1.8%, which is comparable with the general population.
- Information regarding the other new drugs is lacking.
- With the exception of felbamate, which has been associated with aplastic anemia and also hepatic failure, the new antiepileptic drugs do not have major severe side effects.
- The old antiepileptic drugs have been associated with decreased bone mineral content and osteoporosis. This is particularly worrisome in individuals with disabilities, especially if they are nonambulatory. The mechanism in the enzyme inducers is probably related to increased catabolism of vitamin D. However, decreased bone mineral density has also been reported with valproic acid, which is not an enzyme inducer, and also in individuals with normal vitamin D. Whether the new antiepileptic medications might also result in osteoporosis is not clear. Supplementation of the diet with vitamin D might not be sufficient to prevent osteoporosis.
- Felbamate, topiramate, and zonisamide are associated with weight loss. Valproic acid, carbamazepine, gabapentin, and vigabatrin might result in weight gain. Lamotrigine, levetiracetam, and phenytoin do not affect weight.
- On the negative side, the new medications are much more expensive than the old ones and there is no evidence of superior cost-effectiveness.
- The evaluation of cognitive deficiencies due to the use of antiseizure drugs is difficult. This task is even more difficult in persons with intellectual disabilities. A large number of studies address this issue. Unfortunately, the findings of many are inconclusive and even contradictory. However, it seems clear that no single drug causes problems in all patients taking that drug, and all the drugs can result in some form of cognitive impairment in some patients. Also, a subgroup of individuals seem to be at higher risk for cognitive impairment, but at the present time there are no markers to identify that subgroup.
- Very little is known in persons with developmental disabilities because very little research has been conducted in this area.
- The degree of cognitive impairment is probably related to the total dose of the medication, rather than the type of medication.
- The effect occurs while the patient is taking the medication, and in most instances, patients return to baseline after the medications is discontinued.
- Among the old drugs, phenobarbital and the benzodiazepines were considered the most prone to produce some cognitive deficiencies.
- Among the new drugs, topiramate seems to cause more cognitive problems, while lamotrigine seems to be safer. However, more studies are needed to evaluate the cognitive effects of the new drugs.
- In general, the cognitive effects are more often seen in polypharmacy. In persons with intractable seizures and multiple medications, cognitive impairment is a limiting factor in the use of antiepileptic medication.
- In some cases, the use of antiepileptic medications has been associated with improvement in cognitive function and degree of alertness. This could be the result of a positive psychotropic effect of the medications or just more effective seizure control.
- In general, when these medications are used within standard dose, the cognitive impairment added by the medication is minimal.
- Measuring serum levels of the antiepileptic medications routinely has become an integral part of the treatment of epileptic seizures even though the therapeutic levels often do not correlate with an individual's response. However, titration and determination of the dose of medication should not be done on the basis of the serum levels, and unfortunately this is a common practice. The serum level is more useful when poor compliance is suspected or to evaluate the interactions between medications. Some serum levels might be confusing and might lead to wrong therapeutic decisions. For example, serum levels of total phenytoin in persons also taking valproic acid might be low, while the free phenytoin might be high. There are therapeutic values for the old drugs, but there are no such values for the new drugs, and the benefits of the use of serum levels to determine therapeutic effect of the new drugs is minimal.
- Periodic adjustments of the medications might be needed. No fixed guidelines indicate how to proceed. The author recommends closely examining the number of seizures and side effects. Quality of life is an important issue. In many instances, an aggressive attempt to control the number of seizures with a high dose of antiepileptic medications or polypharmacy might result in a decrease in the quality of life. Seizure control and quality of life should be balanced, and the input of other people who are familiar with the patient should be requested. Guidelines may be established based on clinical criteria rather than blood levels of medication.
- Dose adjustments have been established under certain conditions. Gabapentin and levetiracetam are not metabolized in the liver and are good drugs in the presence of liver damage. However, because they are excreted through the kidneys, the dose should be decreased in individuals with kidney damage. For these drugs, guidelines based on creatinine clearance have been established.
- In the presence of kidney insufficiency, the half-life of topiramate, oxcarbazepine, and zonisamide is prolonged. Although guidelines are not established, the dose should be decreased. Blood levels are not necessarily useful but might help to identify changes in the pharmacokinetics of the drug involved.
- Valproic acid has a recognized liver toxicity and might be dangerous to use in persons with history of viral hepatitis.
Surgical Care
This is a valid option for persons with mental retardation. Consider surgery in every case of epileptic disorder that is resistant to antiepileptic drugs.
- The presurgical evaluation is similar to the one performed in individuals without mental retardation.
- Hemispheric surgery is indicated in individuals with intractable seizures and diffuse hemispheric disease. Anatomic hemispherectomy, the removal of the hemisphere, was the first approach; however, because of complications with other techniques, such as subtotal resection, functional hemispherectomy and hemidecortication were developed. Hemispherectomy has been indicated in cases of Sturge-Weber syndrome, hemimeganencephaly, infantile hemiplegia, cortical dysplasi, Rasmussen encephalitis, and infarction. In general, the results are encouraging, with some series showing complete seizure control in 50-79% of the patients who have undergone operation and in most of these patients the AED was discontinued.
In spite of the improvement in the operative techniques, complications do occur in a small number of individuals. The most common complications are intracranial bleeding and hydrocephalus requiring shunt treatment, and a few cases of postoperative headaches and chronic intracranial hypertension. Contralateral hemiparesis affecting mostly the hand function, but with some preservation of proximal upper limb function, and homonymous hemianopsia are usually present after the operation. The prognosis varies with the etiology of the epileptic disorder. Epileptic disorders secondary to vascular etiology have better prognosis, while malformation of cortical development, hemimegalencephaly, and Rasmussen encephalitis have a worse prognosis. Younger age at time of surgery might improve the prognosis in terms of future development, probably by limiting the effect of the epileptic disorder on the nonoperated hemisphere. - Focal resections can be useful in patients with cortical focal dysplasias or tuberous sclerosis.
- Callosotomy might be useful in patients with intractable seizure and predominance of the atonic type of seizures. Complete callosotomy seems to be more effective than partial anterior corpus callosotomy. A recent series showed that at least a 75% reduction in seizures occurred in 75% of the total callosotomy patients compared with 55% of the partial callosotomy patients. No prolonged neurologic deficits were observed in either group and treatment for secondary generalized intractable seizures not amenable to focal resection in children. No disconnection syndrome has been described in children with callosotomies performed before the age of 10 years.
- Multiple subpial transection is to be considered when the seizure foci is in or near eloquent cortex, (eg, in the Landau-Klefner syndrome). This might also be useful in cases with multifocal epileptic foci not amenable to surgical excision.
- Vagal nerve stimulation (VNS) has not been widely used in children with mental retardation and epilepsy, mostly in children with Lennox-Gastaut syndrome in whom this treatment seems to be effective. VNS does not seems to be effective in infantile spasm. Regarding specific seizure types, VNS seems to be more effective in the drop attacks, with some children being seizure-free, and it is also effective, but much less, in individuals with focal epilepsy. At the present time, VNS seems to be indicated in children with drug-resistant epilepsy who are not candidates for surgical resection. Whether VNS would be better that total callosotomy for children with drop attacks is not clear.
Diet
- Ketogenic diet
- This diet was first used for the treatment of epilepsy in the 1920s. Implementing the diet is difficult as are managing its side effects. At the present, the ketogenic diet is indicated in patients with refractory epilepsy.
- The ketogenic diet is more effective in children younger than 12 years than in adolescents or adults.
- Even with advanced dietary techniques the ketogenic diet requires a high level of commitment from the parents and the patients, which limits the use of the diet to a select group of patients.
- This is an option to be considered in children with refractory epilepsy in whom the antiseizure medications are not effective or are toxic.
Activity
The limitation in activities is similar to that for any other person with epilepsy.
Medication
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Anticonvulsants
These agents prevent seizure recurrence and may terminate clinical and electrical seizure activity.
Carbamazepine (Tegretol, Carbatrol)
First-line antiepileptic medication for partial seizures as well as for generalized tonic-clonic seizures.
Adult
200 mg PO bid initially; increase weekly in increments of 200 mg; depending upon pharmaceutical preparation, should be used bid/tid; not to exceed approximately 2000 mg/d
Pediatric
10 mg/kg/d PO initially; increase weekly; not to exceed 20-25 mg/kg/d
Do not coadminister with MAOIs; danazol may increase serum levels significantly if given within 30 d (avoid coadministration whenever possible); cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; may decrease primidone and phenobarbital levels, either may increase carbamazepine levels
Documented hypersensitivity; history of bone marrow depression; MAOI use within last 14 d
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Do not use to relieve minor aches or pains; caution with increased intraocular pressure; obtain CBCs and serum iron baseline prior to treatment, during first 2 months, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision, use caution while driving or performing other tasks requiring alertness
Ethosuximide (Zarontin)
First choice in treatment of simple absences. Also effective in treatment of myoclonic seizures as well as atonic-akinetic seizures.
Adult
250 mg PO bid; titrate to 1500 mg
Pediatric
<3 years: Not recommended
>3 years: Start with small dose, around 5 mg/kg/d PO; increase slowly; not to exceed 20-25 mg/kg/d
Phenytoin, carbamazepine, primidone, or phenobarbital may decrease effects; isoniazid may inhibit hepatic metabolism, increasing toxicity
Documented hypersensitivity; blood dyscrasias; renal or hepatic disease
Pregnancy
D - Unsafe in pregnancy
Precautions
Blood dyscrasias, which may be fatal, may occur; monitor CBC; caution in hepatic or renal disease; abrupt withdrawal of drug may precipitate absence status
Felbamate (Felbatol)
Can be effective in different types of seizures. Because of severe adverse effects, use is limited to those patients in whom no other medication is effective. Felbamate is particularly effective in Lenox-Gastaut syndrome.
Adult
300 mg PO qid or 400 mg PO tid initially as monotherapy; increase dose gradually by 600 mg q2wk; not to exceed 3.6 g/d
Pediatric
<2 years: Not established
2-14 years: 15 mg/kg/d PO in 3-4 divided doses initially; increase by 15 mg/kg/d qwk to 45 mg/kg/d
>14 years: Administer as in adults
May increase steady-state phenytoin levels; 40% dose-reduction of phenytoin may be necessary in some patients; phenytoin may double felbamate clearance, resulting in more than 45% decrease in steady-state levels; coadministration of felbamate and phenobarbital may cause increase in phenobarbital plasma concentrations; phenobarbital may reduce plasma felbamate levels; felbamate may decrease steady-state carbamazepine levels and increase steady-state carbamazepine metabolite levels; felbamate may increase steady-state valproic acid levels
Documented hypersensitivity; blood dyscrasia; hepatic dysfunction
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Associated with marked increase in incidence of aplastic anemia (monitor CBC periodically); marked increase in fatal hepatic failure reported in patients receiving felbamate; perform liver function testing (ALT, AST, bilirubin) before felbamate therapy and at 1- to 2-wk intervals during therapy; discontinue immediately if liver abnormalities detected during treatment
Gabapentin (Neurontin)
Introduced as adjuvant in treatment of partial seizures with and without secondary generalization. Might also be effective in generalized tonic-clonic seizures. Not effective in absence seizures.
Adult
300 mg PO tid recommended initially; increase to 600 mg tid; if necessary and no adverse effects, may increase up to 4000 mg/d
Manufacturer recommendations for impaired kidney function:
CrCl >60 mL/min, 400 mg PO tid
CrCl 30-60 mL/min, 300 mg PO bid
CrCl 15-30 mL/min, 300 mg qd
CrCl <15 mL/min, 300 mg qod
Hemodialysis: supplement dose with 200-300 mg
Pediatric
<12 years: Not established
>12 years: Not established; may start with small dose of 300 mg/d PO and increase weekly depending upon tolerance and clinical effect
Antacids may reduce bioavailability significantly (administer at least 2 h following antacids); may increase norethindrone levels significantly
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in severe renal disease (use smaller dose in persons with renal insufficiency); drowsiness is dose dependent; dizziness, ataxia, fatigue, and nystagmus may occur
Lamotrigine (Lamictal)
Recently introduced. Effective as adjunct and primary drug in management of partial seizures. Also effective in generalized seizures. Indicated in patients aged 2-12 y with Lennox-Gastaut syndrome.
Adult
<16 years: Not established
>16 years: Start with 50 mg PO qd for 2 wk, then 50 mg bid for 2 wk; depending upon tolerance, increase weekly up to 300-500 mg/d; if patient is on valproic acid then use half this dose
Pediatric
Not established; start with small doses of 12.5 mg/d PO and increase slowly at 2-wk intervals
Acetaminophen increases renal clearance, decreasing effects; similarly, phenobarbital and phenytoin increase metabolism, causing decrease in levels; valproic acid increases half-life
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Several cases of Stevens-Johnson syndrome reported; 1% of children (<16 y) and 0.3% of adults may develop rashes; few deaths related to toxic epidermal necrolysis; should be discontinued at first indication of rash; behavior problems can be induced in persons with brain damage; safety in children <16 y, other than those with Lennox-Gastaut syndrome, has not been established
Levetiracetam (Keppra)
Indicated as adjunctive therapy in treatment of partial onset seizures.
Adult
500 mg PO bid initially; increase by 1000 mg/d q2wk; not to exceed 3000 mg/d
Dose change in people with renal damage according to creatinine clearance:
CrCl 50-80 mL/min, 500-1000 mg PO q12h
CrCl 30-50 mL/min, 250-750 mg PO q12h
CrCl <30 mL/min, 250-500 mg PO q12h
End stage renal disease on dialysis: 500-1000 mg/d PO; supplement by 250-500 mg after dialysis
Pediatric
<16 years: Not established
>16 years: Administer as in adults
None reported
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Excreted in breast milk; physicians are encouraged to contact Antiepileptic Drug Pregnancy Registry (888-233-2334) and report women exposed to levetiracetam during pregnancy
Caution in renal impairment; major side effects include somnolence, asthenia, incoordination, mild leukopenia (3%), and behavioral changes such as anxiety, hostility, emotional lability, depression and psychosis (1-2%), and depersonalization
Oxcarbazepine (Trileptal)
The pharmacologic activity of oxcarbazepine is primarily by the 10-monohydroxy metabolite (MHD) of oxcarbazepine. May block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. The anticonvulsant effect may also occur by affecting potassium conductance and high-voltage activated calcium channels. Drug pharmacokinetics are similar in older children (>8 y) and adults. Young children (<8 y) have a 30-40% increased clearance compared with older children and adults. Children <2 y of age have not been studied in controlled clinical trials.
Adult
300 mg PO bid initially; increase 300 mg/d qwk; 1200 mg/d maintenance dose
Renal impairment: CrCl <30 mL/min, 300 mg/d PO initially
Pediatric
<4 years: Not established
4-16 years: 4-5 mg/kg/d PO initially; increase by 5 mg/kg/d qwk; 20-30 mg/kg/d maintenance dose
Renal impairment: Initial dose should be lower and increased slowly
>16 years: Administer as in adults
May decrease levels of dihydropyridine calcium antagonists and oral contraceptives; can reduce serum concentrations of carbamazepine, phenobarbital, phenytoin, and valproic acid; when oxcarbazepine is given in doses >1200 mg/d may increase phenytoin and phenobarbital serum concentrations significantly; oxcarbazepine can reduce serum concentrations of oral contraceptives and make oral contraceptives ineffective; can increase clearance of felodipine; not to be used while nursing
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Can cause cognitive adverse effects (eg, psychomotor slowing, impaired concentration, impaired speech, impaired language); decrease initiation dose by 50% with renal impairment (CrCl <30 mL/min) and increase dose more slowly; oxcarbazepine can cause hyponatremia (sodium <125 mmol/L); among persons with hypersensitivity to carbamazepine, 25-30% have hypersensitivity to oxcarbazepine; rapid withdrawal of oxcarbazepine can cause exacerbation of seizures; observe for side effects and monitor plasma levels of concomitant anticonvulsants during dose titration
Phenobarbital (Barbital, Luminal)
Oldest antiepileptic medication. Effective in partial seizures, generalized tonic, and tonic-clonic seizures. Not effective in absence, atonic akinetic seizures.
Adult
200-260 mg/d PO qd; titrate slowly
Pediatric
1-4 mg/kg/d PO; titrate slowly
Alcohol may produce additive CNS effects and death; may decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients with coagulation parameters stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); chloramphenicol, valproic acid, and MAOIs may increase toxicity; rifampin may decrease effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy); menstrual irregularities also may occur
Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritis
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; caution in myasthenia gravis and myxedema
Phenytoin (Dilantin)
One of oldest antiepileptic drugs. Effective for generalized as well as focal seizures. Not effective in absence seizures, poorly effective in akinetic seizures.
Adult
150-300 mg PO qd
Pediatric
5 mg/kg/d PO initially; increase slowly to 10-15 mg/kg/d
Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase toxicity
Barbiturates, diazoxide, ethanol (long-term ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate may decrease effects
May decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, valproic acid
Documented hypersensitivity; sinoatrial block; second- or third-degree AV block; sinus bradycardia; Adams-Stokes syndrome
Pregnancy
D - Unsafe in pregnancy
Precautions
Rapid IV infusion may result in death from cardiac arrest, marked by QRS widening
Perform blood counts and urinalyses when therapy is begun and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if skin rash appears and do not resume use if rash is exfoliative, bullous, or purpuric; caution in acute intermittent porphyria and diabetes (may elevate blood glucose); discontinue use if hepatic dysfunction occurs
Primidone (Mysoline)
Effective in generalized tonic, tonic-clonic, or partial seizures. Not effective in absence seizures.
Adult
125 mg PO hs; titrate slowly by increasing q3-4d; usually 250 mg PO tid is enough; not to exceed 2000 mg
Pediatric
50 mg PO hs initially, increase slowly; not to exceed 20-25 mg/kg/d
Alcohol may produce additive CNS effects and death; may decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients with coagulation parameters stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); chloramphenicol, valproic acid, and MAOIs may increase toxicity; rifampin may decrease effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy); menstrual irregularities also may occur
Documented hypersensitivity; porphyria; severe respiratory disease; marked impairment of liver function; nephritis
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; caution in myasthenia gravis and myxedema
Tiagabine (Gabitril)
Mechanism of antiseizure action unknown. Believed related to ability to enhance activity of GABA, major inhibitory neurotransmitter in CNS. May block GABA uptake into presynaptic neurons, making more GABA available for receptor binding on surfaces of postsynaptic cells and possibly preventing propagation of neural impulses that contribute to seizures by GABA-ergic action.
It is indicated as adjunct medication in the treatment of partial seizures. Modification of concomitant antiepilepsy drug doses not necessary, unless clinically indicated.
Adult
4 mg/d PO initially, may increase qwk by 4-8 mg/d; not to exceed 56 mg/d
Pediatric
<12 years: Not established
>12 years: 4 mg/d PO initially; may be increased by 4 mg/d qwk; not to exceed 32 mg/d
Cleared more rapidly in patients treated with carbamazepine, phenytoin, primidone, or phenobarbital than in patients who have not received these drugs
Documented hypersensitivity; rash; hepatic impairment
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Patients receiving valproate monotherapy may require lower doses or slower dose titration of tiagabine for clinical response; moderately severe to incapacitating generalized weakness has been reported following administration of tiagabine in as many as 1% of patients with epilepsy; weakness may resolve after reduction in dose or discontinuation; should be withdrawn slowly to reduce potential for increased seizure frequency; may result in stupor or spike wave stupor; CNS depression, poor concentration, fatigue, and somnolence may occur; may exacerbate EEG abnormalities; sudden death and status epilepticus reported; adverse reactions include dizziness, asthenia, somnolence, nausea, and abdominal pain
Topiramate (Topamax)
Sulfamate-substituted monosaccharide with broad spectrum of antiepileptic activity that may have state-dependent sodium channel blocking action. Potentiates inhibitory activity of neurotransmitter GABA. May block glutamate activity.
Adult
50 mg PO qd pm for 1 wk; titrate in increments of 50 mg bid qwk; doses >400 mg/d do not improve responses
Pediatric
Not established; start with small dose of 25 mg/d PO and increase q2wk
On occasions, addition of topiramate to phenytoin may require adjustment of phenytoin dose to achieve optimal clinical outcome; phenytoin, carbamazepine, and valproic acid can decrease levels significantly; reduces digoxin and norethindrone levels; carbonic anhydrase inhibitors may increase risk of renal stone formation, and coadministration should be avoided; coadminister with CNS depressants only with extreme caution because may have additive effect in CNS depression as well as other adverse cognitive or neuropsychiatric events
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Risk of kidney stone formation increased 2-4 times that of untreated population; risk may be reduced by increasing fluid intake; caution in renal or hepatic impairment; open angle glaucoma; hypohidrosis; not necessary to monitor plasma concentrations to optimize therapy (trough plasma concentrations do not correlate with clinical responses)
Valproic acid (Depakene), divalproex sodium (Depakote)
Considered one of main antiepileptic medications. Effective in many different types of seizure disorders, primary or secondary. Particularly effective in treatment of akinetic-atonic seizures and typical and atypical absences. Dosing regimen variable.
Adult
1500-2000 mg PO; 3000 mg or more can be used if tolerated
Pediatric
10-15 mg/kg/d PO initially; may increase to 60 mg/kg/d
Cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may reduce levels significantly; in children, salicylates decrease protein binding and metabolism; may result in variable changes of carbamazepine concentrations with possible loss of seizure control; may increase diazepam and ethosuximide toxicity (monitor closely); may increase phenobarbital and phenytoin levels, while either may decrease valproate levels; may displace warfarin from protein-binding sites (monitor coagulation tests); may increase zidovudine levels in HIV-seropositive patients
Documented hypersensitivity; hepatic disease/dysfunction
Pregnancy
D - Unsafe in pregnancy
Precautions
Thrombocytopenia and abnormal coagulation parameters have occurred; risk of thrombocytopenia increases significantly at total trough valproate plasma concentrations >110 mcg/mL in females and >135 mcg/mL in males; at periodic intervals and prior to surgery, determine platelet counts and bleeding times before initiating therapy; reduce dose or discontinue therapy if hemorrhage, bruising, or hemostasis/coagulation disorder occurs
Hyperammonemia may occur, resulting in hepatotoxicity; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause drowsiness
Zonisamide (Zonegran)
Indicated for adjunctive treatment of partial seizures with or without secondary generalization. Evidence indicates that it is effective in myoclonic and other generalized seizure types as well.
Adult
100 mg/d PO initially for 2 wk; increase by 100 mg/d PO q2wk; not to exceed 400 mg/d
Pediatric
<16 years: Not established
>16 years: Administer as in adults
May cause drowsiness, weight loss, ataxia, nausea, and slowing of mental activity; pediatric patients have an increased risk for oligohidrosis and hyperthermia
Documented hypersensitivity
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
May increase serum carbamazepine levels; carbamazepine may increase zonisamide concentrations; phenobarbital may decrease zonisamide levels; not for use in nursing women
More on Epilepsy in Children with Mental Retardation |
| Overview: Epilepsy in Children with Mental Retardation |
| Differential Diagnoses & Workup: Epilepsy in Children with Mental Retardation |
 Treatment & Medication: Epilepsy in Children with Mental Retardation |
| Follow-up: Epilepsy in Children with Mental Retardation |
| References |
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Further Reading
Keywords
antiepileptic medications, anti-epileptic medications, epilepsy in children with mental retardation, epilepsy in MR, epilepsy in mental retardation
