Principles of Antiepileptic Drug Treatment

The selection of an AED is based on efficacy against specific seizure types and the potential for producing adverse effects ( Ta.ble.52.:6. ). First-line agents against TCS include phenytoin, carbamazepine, and valproic acid. Ethosuximide and valproic acid are effective against AS. Valproic acid is the only primary drug effective against tonic-clonic, absence, and myoclonic seizures, making it the drug of choice for JME. Myoclonic seizures are responsive to valproic acid and benzodiazepines. Carbamazepine and phenytoin, followed by valproic acid, are the drugs of choice in the treatment of partial seizures. Although primidone

1081

TABLE 52-6 -- ANTIEPILEPTIC AGENTS FOR SPECIFIC SEIZURE TYPES

Seizure Type

First-line Agents

Adjunctive Agents

Tonic-clonic

Phenytoin

Phenobarb

tal

Carbamazepine

Primidone

Valproic acid

Lamotrigine

Absence

Ethosuximide

Benzodiazepines

Valproic acid

Lamotngine

Acetazolamide

Myoclonic

Valproic acid

Lamotrigine

Benzodiazepines

Tonic/atonic

Valproie acid

Lamotrigine

Benzodiazepines

Focal (partial)

Carbamazepine

Gabapentin

Phenytoin

Lamotrigine

Valproic acid

Phenobarbital/primidone

and phenobarbital are effective against tonic-clonic and partial seizures, they are not considered first-line agents because of their sedative properties. In controlled trials, lamotrigine and gabapentin produced a 30 to 50 percent reduction in seizures in approximately one third of patients with partial epilepsy. 4ij , y Lamotrigine may also be effective against generalized seizures in patients with idiopathic generalized epilepsy and Lennox-Gastaut's syndrome. In unpublished series, topiramate proved to be effective as adjunctive therapy in adults with partial seizures, reducing seizure frequency by 50 percent in approximately 50 percent of patients. '43] Felbamate has a broad spectrum of action but is no longer indicated for routine use because of hematologic and hepatic toxicity. The potential for long-term complications has not been established for newer AEDs, and their cost is significantly greater than the older agents.

Dose-related adverse effects commonly occur in patients taking anticonvulsant medication and usually resolve spontaneously or with reduction in dosage or discontinuation of the drug. Gastrointestinal distress and dizziness are frequently reported with primidone, carbamazepine, valproic acid, and ethosuximide. Nystagmus, dysarthria, diplopia, and ataxia are associated with phenytoin, carbamazepine, primidone, and phenobarbital. The benzodiazepines, phenobarbital, primidone, and phenytoin may produce sedation and cognitive impairment. Dizziness, headache, diplopia, and ataxia are the most common adverse effects associated with lamotrigine. Somnolence, dizziness, ataxia, fatigue, and nystagmus may be observed with gabapentin. The institution of felbamate is usually associated with GI disturbances that occasionally require drug withdrawal.

Skin eruptions represent the most commonly encountered idiosyncratic reaction associated with AEDs. Generally appearing within the first 3 months of treatment, rashes are usual benign, and they resolve with dosage reduction or discontinuation. Severe reactions including Stevens-Johnson syndrome, exfoliative dermatitis, and toxic epidermal neurolysis occur rarely. Antiepileptic drugs can produce megaloblastic anemia, leukopenia, thrombocytopenia, aplastic anemia, asymptomatic elevations of hepatic transaminases, and life-threatening hepatotoxicity. Chronic idiosyncratic reactions include disorders of connective tissue and nervous system, endocrinopathies, and autoimmune disease.

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