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1 3 2 2
14 21 days 4 7 days 4 5 days 4 days
10 40 mcg/mL 5 15 mcg/mL
Oxcarbazepine1,3 Levetiracetam1 Zonisamide1
900 1800 mg 1000 3000 mg 200 600 mg
2 2 1 2
2 3 days 2 days 10 days
Tiagabine1 Pregabalin1
32 56 mg 150 160 mg
2 days 2 4 days
Gabapentin1 Felbamate
1,3,6
900 1800 mg 1200 3600 mg
1 day 4 5 days
Absence (petit mal) seizures Ethosuximide 100 1500 mg 2 5 10 days 40 100 mcg/mL
Valproic acid Clonazepam Myoclonic seizures Valproic acid Clonazepam
1500 2000 mg 004 02 mg/kg
2 4 days
50 100 mcg/mL 20 80 ng/mL
1500 2000 mg 004 02 mg/kg
2 4 days
50 100 mcg/mL 20 80 ng/mL
Approved as adjunctive therapy for partial-onset seizures Approved as adjunctive therapy for primary generalized tonic-clonic seizures 3 Approved as initial monotherapy for partial-onset seizures 4 Approved as initial monotherapy for primary generalized tonic-clonic seizures 5 Approved as monotherapy (after conversion from another drug) in partial-onset seizures 6 Not to be used as a first-line drug; when used, blood counts should be performed regularly (every 2 4 weeks) Should be used only in selected patients because of risk of aplastic anemia and hepatic failure It is advisable to obtain written informed consent before use
Nervous System Disorders
cause aplastic anemia or fulminant hepatic failure, should be used only in selected patients unresponsive to other measures Tiagabine is another adjunctive agent for partial seizures In most patients with seizures of a single type, satisfactory control can be achieved with a single anticonvulsant drug Treatment with two drugs may further reduce seizure frequency or severity, but usually only at the cost of greater toxicity Treatment with more than two drugs is almost always unhelpful unless the patient is having seizures of different types 2 Monitoring Monitoring serum drug levels has led to major advances in the management of seizure disorders The same daily dose of a particular drug leads to markedly different blood concentrations in different patients, and this will affect the therapeutic response In general, the dose of an antiepileptic agent is increased depending on the clinical response regardless of the serum drug level The trough drug level is then measured to provide a reference point for the maximum tolerated dose Dosing should not be based simply on serum levels because many patients require levels that exceed the therapeutic range ( toxic levels ) but tolerate these without ill effect Steady-state drug levels in the blood should be measured after treatment is initiated, dosage is changed, or another drug is added to the therapeutic regimen and when seizures are poorly controlled Dose adjustments are then guided by the laboratory findings The most common cause of a lower concentration of drug than expected for the prescribed dose is poor patient compliance Compliance can be improved by limiting to a minimum the number of daily doses Recurrent seizures or status epilepticus may result if drugs are taken erratically, and in some circumstances noncompliant patients may be better off without any medication All anticonvulsant drugs have side effects, and some of these are shown in Table 24 3 In most patients, a complete blood count should be performed at least annually because of the risk of anemia or blood dyscrasia Treatment with certain drugs may require more frequent monitoring or use of additional screening tests For example, periodic tests of hepatic function are necessary if valproic acid, carbamazepine, or felbamate is used, and serial blood counts are important with carbamazepine, ethosuximide, or felbamate 3 Discontinuance of medication Only when patients have been seizure-free for several (at least 3) years should withdrawal of medication be considered Unfortunately, there is no way of predicting which patients can be managed successfully without treatment, although seizure recurrence is more likely in patients who initially failed to respond to therapy, those with seizures having focal features or of multiple types, and those with continuing electroencephalographic abnormalities Dose reduction should be gradual over a period of weeks or months, and drugs should be withdrawn one at a time If seizures recur, treatment is reinstituted with the same drugs used previously Seizures are no more difficult to control after a recurrence than before 4 Surgical treatment Patients with surgically remediable epilepsy or seizures refractory to pharmacologic manage-
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