Managing seizures: Achieving control while minimizing risk

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Applied Evidence

Managing seizures: Achieving control while minimizing risk

J Fam Pract. 2011 August;60(8):464-472

References

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TABLE W1
A closer look at antiepileptic drugs^19-24

Drug name	Maintenance dosage	Adverse effects		Cost (30-day supply)*
Drug name	Maintenance dosage	Common	Rare/idiosyncratic	Cost (30-day supply)*
First generation
Carbamazepine	800-1200 mg/d	Dizziness, drowsiness, diplopia, nausea, vomiting, diarrhea, rash, pruritus, SIADH	Aplastic anemia, agranulocytosis, hyponatremia, SJS, hepatic failure, pancreatitis, suicidal ideation	$4-$50 (XR: $200)
Ethosuximide	20 mg/kg per day	Sleep disturbance, drowsiness, hyperactivity, behavior changes, headache, nausea, vomiting, hiccups	Agranulocytosis, aplastic anemia, SJS, hepatic failure, serum sickness, suicidal ideation	$40-150
Phenobarbital	1-4 mg/kg per day; 120-400 mg/d	Altered sleep cycles, sedation, ataxia, lethargy, behavior changes, hyperactivity, nausea, rash	Agranulocytosis, dermatitis, SJS, hepatic failure, serum sickness, connective tissue disorders, metabolic bone disease, intellect blunting, suicidal ideation	$4-$10
Phenytoin	300-600 mg/d	Confusion, slurred speech, double vision, ataxia, nystagmus, neuropathy, hirsutism, acne, gingival hyperplasia	Neuropathy, agranulocytosis, SJS, immune reactions/serum sickness, hepatic failure, skin thickening, metabolic bone disease, suicidal ideation	$35
Valproic acid	60-350 mg/kg per day	Tremor, weight gain, PCOS, nausea, vomiting, alopecia, easy bruising	Hepatic failure, pancreatitis, hearing loss, blood dyscrasias/thrombocytopenia, hyperammonemia, encephalopathy, osteoporosis, suicidal ideation	$40 (ER: $150)
Second generation
Felbamate	2400-3600 mg/d	Somnolence, nausea, vomiting, weight loss, anorexia	Aplastic anemia (>13 years), hepatic failure, suicidal ideation	$300-$500^†
Gabapentin	900-1800 mg/d	Somnolence, fatigue, weight gain, nystagmus	Pedal edema, suicidal ideation	$4-$100
Lacosamide	200-400 mg/d	Headache, dizziness, ataxia, nausea, diplopia	Euphoria, prolongation of PR interval, heart block, suicidal ideation	$420^†
Lamotrigine	300-500 mg/d	Dizziness, ataxia, nausea, somnolence, rash	SJS, hypersensitivity reactions (renal/hepatic failure), DIC, suicidal ideation	$30-$100
Levetiracetam	3000 mg/d	Somnolence, dizziness, aggression, agitation, anxiety, weight loss	Infection, pancytopenia, liver failure, suicidal ideation	$30-$100 (XR: $245^†)
Oxcarbazepine	1200 mg/d	Somnolence, fatigue, headache, ataxia, nausea, rash	Hyponatremia, SJS, TEN, angioedema	$250-$1000
Pregabalin	150-600 mg/d	Peripheral edema, dry mouth, dizziness, ataxia, diplopia, weight gain	Angioedema, CK elevation, mild PR interval prolongation, suicidal ideation	$100-$350^†
Rufinamide	3200 mg/d	Headache, dizziness, fatigue, nausea	Shortened QT interval, hypersensitivity rash, suicidal ideation	$400-$750^†
Tiagabine	32-56 mg/d	Difficulty concentrating, dizziness, headache, somnolence, nervousness	Spike-wave stupor, sudden death, suicidal ideation	$140-$650^†
Topiramate	200-400 mg/d	Somnolence, dizziness, fatigue, weight loss, difficulty concentrating, speech problems, paresthesias, diarrhea, nausea	Acute myopia and glaucoma, hyperthermia (children); metabolic acidosis, hyperammonemia, liver failure, oligohydrosis, SJS/TEN, kidney stones, suicidal ideation	$40 - $100
Vigabatrin	1500 mg/d	Fatigue, somnolence, nystagmus, tremor, weight gain	Vision loss (30% of patients) blurred vision, arthralgia, suicidal ideation	:$50 -$100^†
Zonisamide	400- 600 mg/d	Somnolence, difficulty concentrating, anorexia, nausea	SJS, TEN, aplastic anemia, agranulocytosis, nephrolithiasis/, oligohydrosis, acidosis, suicidal ideation	$50-$200
CK, creatine kinase; DIC, disseminated intravascular coagulation; ER, extended release; IV, intravenous; PCOS, polycystic ovarian syndrome; SIADH, syndrome of inappropriate antidiuretic hormone hypersecretion; SJS, Stevens-Johnson syndrome; TEN, toxic epidermal necrolysis, XR, extended release. *Costs from www.drugstore.com, www.savewithgenericdrugs.com, and www.pharmacychecker.com. ^†No generic available.

When to add a second AED

Monotherapy is the preferred method of epilepsy treatment, and controls seizures for 70% to 90% of patients.^31,32 If seizures continue and potential adverse effects prevent you from increasing the dosage, switching to a different AED, then tapering off the first agent, is recommended.^33,34

If the new AED fails to provide adequate seizure control, consider combination therapy. An additional 10% to 15% of patients with epilepsy achieve control with dual therapy.^33,34

Many second-generation agents are approved for adjunctive therapy. However, the use of 2 AEDs increases the risk of toxicities and drug interactions, and requires complex dosage adjustments, which should be done slowly and cautiously. Combination therapy also increases costs and may cause a decrease in compliance.^33,34

Noncompliance is the single most common reason for treatment failure in patients with epilepsy, occurring at an estimated rate of up to 60%.^35,36 The complexity of the drug regimen is the major cause, regardless of patient age, sex, psychomotor development, seizure type, or seizure frequency.^35,36

Because of the lack of good clinical trials of combination antiepilepsy therapy, no evidence is available to indicate which AEDs are safe and effective when taken together. There is, however, evidence that certain combinations should be avoided due to the risk of increased adverse effects. These include phenobarbital/valproate, phenytoin/carbamazepine, and carbamazepine/lamotrigine.²⁵

Managing the patient who is seizure-free

After a patient has been seizure-free for 2 to 5 years, consider a reduction in, or a discontinuation of, his or her AED. The relapse rate varies from 10% to 70%, with meta-analyses showing a rate of 25% in the first year and 29% in the second year.^19,37 The American Academy of Neurology (AAN) has published an evidence-based guideline for discontinuing AEDs in seizure-free patients, available at www.aan.com/professionals/practice/pdfs/gl0007.pdf.

Withdrawal should be gradual and, for patients on combination therapy, carried out one drug at a time to prevent a recurrence of seizures or status epilepticus. The AAN recommends a 2- to- 3-month withdrawal period for AEDs (and longer for benzodiazepines), although relapse rates have been found to be lower when the medication is withdrawn more slowly, over about 6 months.^19,34 If seizures recur after withdrawal, restart the AEDs at previous dosages.^19,34,38