eMedicine Specialties > Neurology > Seizures and Epilepsy

Complex Partial Seizures: Treatment & Medication

Author: Anthony M Murro, MD, Laboratory Director, Professor, Department of Neurology, Medical College of Georgia
Contributor Information and Disclosures

Updated: Oct 11, 2006

Treatment

Medical Care

  • Anticonvulsant therapy is generally indicated when patients have more than 1 seizure.
  • The goal is to make the patient seizure free.
  • Even 1 seizure per year may prevent the patient from working and/or driving.
  • Therapy with 1 agent is generally preferred to therapy with 2 or more anticonvulsants. Cognitive adverse effects are common with anticonvulsants.
  • The newer anticonvulsants gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, and zonisamide have the following characteristics:
    • They are more costly than older anticonvulsants.
    • There are excellent drugs to use when treatment with 2 anticonvulsants is needed because they have minimal hepatic drug interactions.
    • They do not require serum drug-concentration monitoring.
    • They have a high therapeutic index.
    • They are well tolerated and can be used at doses greater than the maximum recommended dose.
  • Although many anticonvulsants are listed as category D (unsafe in pregnancy), the use of anticonvulsants during pregnancy is usually safer for women who require these drugs for seizure control than for others. Valproate is more likely than other anticonvulsants to cause congenital birth defects. The valproate-related congenital birth defect risk is greater at higher valproate doses.
  • Phenytoin and valproate have the following characteristics:
    • They bind strongly to serum proteins.
    • Free drug levels are required if the patient is pregnant or if the patient has abnormal serum protein levels (eg, due to hepatic and/or renal disease).
  • Phenobarbital is not a first-line anticonvulsant because of its sedative qualities.
  • Felbamate is not a first-line anticonvulsant because it has a significantly higher risk of aplastic anemia and hepatic injury than that of other agents.
  • Anticonvulsant drug-level monitoring may be needed.
    • Screening laboratory studies before the start of anticonvulsant therapy may provide information about risk factors, which may be important in selecting an anticonvulsant.
    • Subsequent, periodic blood and urine monitoring in otherwise asymptomatic patients receiving anticonvulsants does not help in identifying patients at risk for life-threatening adverse drug reactions.
    • Mild elevations in transaminase levels and mild depressions in blood cell counts often occur with anticonvulsant therapy. These mild abnormalities do not indicate pending hepatic failure or aplastic anemia, and anticonvulsant therapy is usually continued in otherwise asymptomatic patients.
    • Periodic blood and urine monitoring may be useful in select patients who are at increased risk for life-threatening adverse drug reactions.
    • Periodic blood and urine monitoring may be useful in select patients, such as those with mental disability who are unable to communicate.
  • Patients should be educated about how to recognize the signs of a severe adverse drug reaction.
  • Criteria for anticonvulsant withdrawal are as follows:
    • The patient should have been seizure free for a minimum of 2 years while taking anticonvulsants.
    • The patient has a single type of partial or generalized seizure.
    • Neurologic examination yields normal findings.
    • The patient has a normal IQ.
    • The EEG is normal.

Surgical Care

  • Epilepsy surgery is indicated for patients who have frequent, disabling seizures despite adequate trials of 2 or more anticonvulsants.
  • Surgical procedures include temporal lobectomy, extratemporal resections, corpus callosotomy, placement of a vagus-nerve stimulator, hemispherectomy, and multiple subpial transection.

Consultations

  • Refer the patient to an epilepsy specialist for EEG-video monitoring if his or her history and previous EEGs have been nondiagnostic, refer for EEG-video monitoring.
  • Refer the patient to an epilepsy specialist if the patient has seizures despite previous trials with multiple anticonvulsants.
  • Refer the patient to an epilepsy specialist if the patient is a possible candidate for epilepsy surgery.

Activity

  • All persons with uncontrolled seizures must be advised to refrain from high-risk activities that put themselves and/or others in danger in the event of a seizure. These activities include, but are not limited to the following:
    • Operating a motor vehicle
    • Operating a stove or other dangerous machinery
    • Working at heights
  • Persons with uncontrolled epilepsy should be advised to contact the appropriate state agency regarding driving regulations. Some states require physician reporting of drivers who experience seizures.
  • These activity restrictions should be reviewed in detail (and documented in the medical record) with the patient, family, and/or caregivers.

Medication

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Anticonvulsants

These agents are used to terminate clinical and electrical seizure activity as rapidly as possible and to prevent seizure recurrence.


Carbamazepine (Carbamazepine, Tegretol, Tegretol XR)

Effective for treatment of complex partial seizures. Appears to act by reducing polysynaptic responses and blocking posttetanic potentiation. Major mechanism of action is reducing sustained, high-frequency, repetitive neural firing.

Adult

200 mg PO bid (100 mg qid of suspension); increase qwk by no more than 200 mg/d tid/qid (bid with extended release) until best response; generally not to exceed 1600 mg/d

Pediatric

<6 years: 10-20 mg/kg/d PO bid/tid (qid with suspension); increase qwk to achieve optimal clinical response with tid/qid
6-12 years: 100 mg bid (50 mg qid of suspension); gradually increase qwk by 100 mg/d tid/qid (bid with extended release) until best response; generally not to exceed 1000 mg/d
>12 years: Administer as in adults; generally not to exceed 1000 mg/d in children 12-15 y or 1200 mg/d in adolescents >15 y

Do not use concomitantly with MAOIs; discontinue MAOIs at least 14 d before initiating carbamazepine; may decrease serum concentrations of primidone or phenobarbital, which may increase serum concentration of carbamazepine, possibly because of altered hepatic metabolism; cimetidine may increase plasma levels and toxicity; interaction appears to be most important when cimetidine added during first 4 wk of therapy; use of danazol within 30 d may increase levels 38-123% (avoid concomitant administration if possible)

Documented hypersensitivity; history of bone-marrow depression

Pregnancy

D - Unsafe in pregnancy

Precautions

Not simple analgesic; do not use for relief of minor aches or pains; caution in increased intraocular pressure; manufacturer recommends pretreatment CBC count, including platelets and possibly reticulocytes, and serum iron level; CBC count, platelets, and differential should be performed monthly in first 2 mo and then yearly or every other year; patients should observe caution while driving or performing other tasks requiring alertness, coordination, or physical dexterity (may produce drowsiness, dizziness, or blurred vision); hyponatremia


Phenytoin (Dilantin, Phenytek)

Primary site of action of hydantoins, appears to be motor cortex, where it may inhibit spread of seizure activity. May reduce maximal activity of brainstem, centers responsible for tonic phase of grand mal seizures. Individualize dose. If daily dosage cannot be divided equally, large dose should be taken at bedtime. Phosphorylated formulation (fosphenytoin) available for parenteral use and may be given IM or IV.

Adult

Initial dose: 100 mg (125 mg suspension) PO/IV tid
Maintenance: 300-400 mg/d PO/IV divided tid, or qd/bid if using extended release; increase to 600 mg/d (625 mg/d suspension) may be necessary; not to exceed 1500 mg/24h

Pediatric

Initial dose: 5 mg/kg/d PO/IV divided bid/tid
Maintenance: 4-8 mg/kg PO/IV divided bid/tid
>6 years: May require minimum adult dose (300 mg/d); not to exceed 300 mg/d

Amiodarone, benzodiazepines, chloramphenicol, cimetidine, disulfiram, ethanol (acute ingestion), fluconazole, isoniazid, metronidazole, miconazole, omeprazole, phenacemide, phenylbutazone, succinimides, sulfonamides, trimethoprim, and valproic acid may increase toxicity; barbiturates, carbamazepine, diazoxide, ethanol (chronic ingestion), rifampin, theophylline, antacids, charcoal, and sucralfate may decrease effects; may decrease effects of acetaminophen, amiodarone, carbamazepine, cardiac glycosides, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, methadone, metyrapone, mexiletine, oral contraceptives, quinidine, theophylline, and valproic acid

Documented hypersensitivity; because of effect on ventricular automaticity, do not use in sinoatrial block, sinus bradycardia, second- or third-degree AV block, or Adams-Stokes syndrome

Pregnancy

D - Unsafe in pregnancy

Precautions

Death from cardiac arrest has occurred after too-rapid IV administration, sometimes preceded by marked QRS widening; blood dyscrasias have occurred (manufacturer recommends CBC counts and urinalyses at start and monthly intervals for several months thereafter); discontinue if skin rash appears, and do not resume if rash is exfoliative, bullous, or purpuric; caution in acute intermittent porphyria or diabetes (may raise blood glucose levels); discontinue if hepatic dysfunction occurs


Valproic acid (Depakote, Depakene, Depacon)

Chemically unrelated to other drugs used to treat seizure disorders. Mechanism of action not established, but activity may be related to increased brain levels of GABA or enhanced GABA action. May also potentiate postsynaptic GABA responses, affect potassium channel, or have direct membrane-stabilizing effect.
For conversion to monotherapy, concomitant AED dosage ordinarily reduced by approximately 25% q2wk. Reduction may be started at beginning of therapy or delayed 1-2 wk if seizures likely to occur with reduction. Monitor patients closely during this period for increased seizure frequency.
As adjunctive therapy, divalproex sodium 10-15 mg/kg/d may be added to regimen; dosage may be increased 5-10 mg/kg/d qwk to optimal clinical response (usually with <60 mg/kg/d).

Adult

Monotherapy: 10-15 mg/kg/d PO in 1-3 divided doses; increase by 5-10 mg/kg/wk until seizures controlled or adverse effects prevent further increases; not to exceed 60 mg/kg/d; if total daily dose >250 mg, give in divided doses

Pediatric

Administer as in adults

Cimetidine may slightly but significantly decrease clearance and increase half-life; erythromycin may increase serum concentrations, producing toxicity; felbamate may increase mean peak levels by 35%; rifampin may increase oral clearance by 40%; in children, salicylates decrease protein binding and metabolism
May cause variable changes in carbamazepine concentration with increased levels of active metabolite; carbamazepine may decrease levels, with possible loss of seizure control; displaces diazepam from plasma albumin-binding sites and inhibits metabolism, increasing toxicity; inhibits ethosuximide metabolism, and thus serum levels of both drugs should be monitored, especially in presence of other anticonvulsants; inhibits phenobarbital metabolism; phenobarbital can increase clearance; may increase action of phenytoin, even at therapeutic levels; phenytoin may increase metabolism, with decreased pharmacologic effects; may displace warfarin from protein binding sites (monitor coagulation); may decrease zidovudine clearance in HIV-seropositive patients

Documented hypersensitivity; hepatic disease/dysfunction

Pregnancy

D - Unsafe in pregnancy

Precautions

Thrombocytopenia and abnormal coagulation parameters have occurred; probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations >110 mcg/mL in females and 135 mcg/mL in males; manufacturer recommends determining platelet counts and bleeding time before therapy, at periodic intervals, and before surgery; hemorrhage, bruising, or hemostasis/coagulation disorder indication for dosage reduction or withdrawal; hyperammonemia may occur if patient has increased renal ammonium production and inhibited urea synthesis (combined effect may contribute to hepatotoxicity; pancreatitis possible; closely monitor patients for malaise, weakness, facial edema, anorexia, jaundice, and vomiting; patients should use caution while driving or performing other tasks requiring alertness, coordination, or physical dexterity


Gabapentin (Neurontin)

Has properties in common with other anticonvulsants but exact mechanism of action unknown. Structurally related to GABA but does not interact with GABA receptors.

Adult

Day 1: 100 mg PO tid or 300 mg hs
Day 2: Increase dose to 400 mg PO tid over 3 d and titrate dose prn
Increases in daily dose best tolerated when done slowly; not to exceed 1200 mg qid

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Antacids may reduce bioavailability by about 20% and should be administered at least 2 h before; cimetidine may reduce clearance but may not be of clinical significance; may increase norethindrone levels by 13%

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in severe renal disease


Lamotrigine (Lamictal)

Triazine derivative useful in treatment of seizures and neuralgic pain. Inhibits release of glutamate and inhibits voltage-sensitive sodium channels, which stabilizes neuronal membrane. Follow manufacturer's recommendations for dose adjustments.

Adult

Adjunctive therapy with enzyme-inducing anticonvulsant
Weeks 1-2: 50 mg/d PO
Weeks 3-4: 100 mg/d in 2 divided doses
Maintenance: 300-500 mg/d (in 2 divided doses); to achieve maintenance, increase by 100 mg/d q1-2wk
Adjunctive therapy with anticonvulsant regimen containing valproate
Weeks 1-2: 25 mg PO qod
Weeks 3-4: 25 mg/d
Maintenance: 100-200 mg/d PO qd/bid; to achieve maintenance, increase by 25-50 mg/d PO q1-2wk
Conversion from single enzyme-inducing anticonvulsant to lamotrigine monotherapy
Weeks 1-2: 50 mg/d
Weeks 3-4: 100 mg/d in 2 divided doses
Maintenance: 300-500 mg/d (in 2 divided doses); to achieve maintenance, increase by 100 mg/d PO q1-2wk; enzyme-inducing anticonvulsant gradually withdrawn over 4 wk by 20% decrements q1wk

Pediatric

2-12 years

Adjunctive therapy with enzyme-inducing anticonvulsant
Weeks 1-2: 0.6 mg/kg/d PO in 2 divided doses, rounded down to nearest 5 mg
Weeks 3-4: 1.2 mg/kg/d PO in 2 divided doses, rounded down to nearest 5 mg
Maintenance: 5-15 mg/kg/d; not to exceed 400 mg/d divided bid; to achieve usual maintenance dose, increase subsequent doses q1-2wk as follows: Calculate 1.2 mg/kg/d, round down to nearest 5 mg, and add amount to previous daily dose
As concomitant therapy with valproic acid
Weeks 1-2: 0.15 mg/kg/d PO qd or divided bid, rounded down to nearest 5 mg; if initially calculated daily dose is 2.5-5 mg, then 5 mg PO qod for first 2 wk
Weeks 3-4: 0.3 mg/kg/d PO qd or divided bid, rounded down to nearest 5 mg
Maintenance: 1-5 mg/kg/d PO; not to exceed 200 mg/d qd or divided bid; to achieve usual maintenance dose, increase subsequent doses q1-2wk as follows: Calculate 0.3 mg/kg/d, round down to nearest 5 mg, and add amount to previous qd dose

>12 years

As adjunctive therapy with enzyme-inducing anticonvulsant
Weeks 1-2: 50 mg/d
Weeks 3-4: 100 mg/d PO divided bid
Maintenance: 300-500 mg/d PO divided bid; to achieve maintenance, increase by 100 mg/d q1-2wk
As concomitant therapy with valproic acid
Weeks 1-2: 25 mg PO qod
Weeks 3-4: 25 mg PO qd
Maintenance: 100-400 mg/d PO qd or divided bid; to achieve maintenance, increase by 25-50 mg/d PO q1-2wk

Acetaminophen increases renal clearance, decreasing effects; phenobarbital and phenytoin increase metabolism, decreasing levels; valproic acid increases half-life

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in impaired renal or hepatic function; rash in 5% of patients; children who take with valproate have significantly increased risk of severe allergic drug reactions


Topiramate (Topamax)

Sulfamate-substituted monosaccharide with broad spectrum of antiepileptic activity; may have state-dependent sodium channel blocking action; potentiates inhibitory activity of neurotransmitter GABA. May block glutamate activity. Monitoring plasma concentrations not necessary to optimize therapy. If added to phenytoin, may need to adjust phenytoin dose to achieve optimal clinical outcome.

Adult

50 mg/d PO; titrate by 50 mg/d qwk to target dose of 200 mg PO bid; not to exceed 1600 mg/d

Pediatric

Not established

Phenytoin can decrease levels by as much as 48%; carbamazepine and valproic acid reduce levels by 40% and 14%, respectively; reduces digoxin and norethindrone levels; carbonic anhydrase inhibitors may increase risk of renal stone formation and should be avoided; may have additive effect with CNS depressants in CNS depression and other cognitive or neuropsychiatric adverse effects

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Increases risk of kidney stone by 2-4 times that of untreated population (1.5%); increasing fluid intake may reduce this risk; caution in renal or hepatic impairment


Tiagabine (Gabitril)

Mechanism of action in antiseizure effect unknown but thought related to its ability to enhance activity of GABA, major inhibitory neurotransmitter in CNS. May block GABA uptake into presynaptic neurons, increasing GABA for receptor binding on surfaces of postsynaptic cells and possibly preventing propagation of neural impulses that contribute to seizures by GABAergic action. Modification of concomitant AED doses not necessary unless clinically indicated.

Adult

4 mg PO qd in 2 or 4 divided doses; increase 4-8 mg/wk until clinical response achieved or total daily dose of 56 mg/d; Doses >56 mg/d not systematically evaluated in well-controlled trials

Pediatric

<12 years: Not established
12-18 years: 4 mg PO qd; increase by 4 mg at beginning of wk 2; thereafter, may increase total daily dose by 4-8 mg/wk until clinical response achieved or 32 mg/d administered
Doses >32 mg/d tolerated in small number of adolescent patients for relatively short duration

Hastened clearance in patients treated with carbamazepine, phenytoin, primidone, or phenobarbital

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Patients receiving valproate monotherapy may require low doses or slow dose titration for clinical response; moderately severe to incapacitating generalized weakness reported in as many as 1% of patients with epilepsy; weakness may resolve after dose reduction or discontinuation; withdraw slowly to reduce potential for increased seizure frequency


Felbamate (Felbatol)

Oral AED with weak inhibitory effects on GABA receptor binding and benzodiazepine receptor binding but interacts as antagonist at strychnine-insensitive glycine recognition site of NMDA receptor-ionophore complex. Not indicated as first-line antiepileptic treatment. Recommended only in those patients whose epilepsy is so severe that benefits outweigh risks of aplastic anemia or liver failure.

Adult

Monotherapy
Initial dose: 1200 mg/d PO divided tid/qid; titrate to 2400 mg/d by 600-mg q2wk and to 3600 mg/d if clinically indicated
Conversion to monotherapy
Initial dose: 1200 mg/d PO divided tid/qid
Week 1: Reduce dose of concomitant AEDs by one third at start
Week 2: Increase dosage to 2400 mg/d while reducing dosage of other AEDs by additional one third of original dosage
Week 3: Increase dosage up to 3600 mg/d and continue to reduce dosage of other AEDs prn
Adjunctive therapy
Week 1: 1200 mg/d PO and reduce dose of concomitant AEDs
Week 2: 2400 mg/d PO and reduce original AED doses by 33%
Week 3: 3600 mg/d PO and reduce AED doses as clinically indicated

Pediatric

<14 years: Not established
Adjunctive therapy
2-14 years: 15 mg/kg/d PO divided tid/qid while reducing AED doses by 20% to control plasma levels of concurrent phenytoin, valproic acid, phenobarbital, and carbamazepine (and metabolites)
Increase felbamate dosage by 15 mg/kg/d PO qwk to 45 mg/kg/d; most adverse effects during adjunctive therapy resolve as dosage of concomitant AEDs decreased
>14 years: Administer as in adults

May increase steady-state phenytoin levels (reduction of phenytoin dose by as much as 40% may be necessary); phenytoin may double felbamate clearance, resulting in >45% decrease in steady-state levels; may increase phenobarbital plasma concentrations; phenobarbital may reduce plasma levels; may decrease steady-state carbamazepine levels and increase steady-state carbamazepine metabolite levels; may increase steady-state valproic acid levels

Documented hypersensitivity; history of any blood dyscrasia or hepatic dysfunction

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Associated with marked increase in incidence of aplastic anemia (risk may be greatest during first year of therapy); manufacturer recommends periodic CBC count monitoring; increases risk of hepatic failure resulting in death; manufacturer recommends liver function testing (ALT, AST, bilirubin) before start and then q1-2wk during therapy; immediately discontinue if any liver abnormalities detected during treatment


Phenobarbital (Luminal)

Anticonvulsant activity at anesthetic doses and can be administered orally. If IM chosen, should be injected into large muscle, eg, gluteus maximus, vastus lateralis, or other areas with little risk of encountering nerve trunk or major artery. Injection into or near peripheral nerves may result in permanent neurologic deficit.
Restrict IV use to conditions in which other routes not feasible because patient unconscious (eg, cerebral hemorrhage, eclampsia, status epilepticus) or when prompt action imperative

Adult

PO: 60-100 mg/d
IV or IM: 200-320 mg q6h prn

Pediatric

PO: 3-6 mg/kg/d
IV or IM: 4-6 mg/kg/d for 7-10 d to blood level of 10-15 mcg/mL, or 10-15 mg/kg/d

Alcohol may produce additive CNS effects and death; chloramphenicol may inhibit metabolism (phenobarbital may enhance chloramphenicol metabolism); MAOIs may enhance sedative effects; rifampin induces hepatic microsomal enzymes and may decrease effectiveness; valproic acid may decrease metabolism and increase toxicity; can decrease effects of anticoagulants (patients whose PT/aPTT stabilized with anticoagulants may require dosage adjustments if phenobarbital added to or withdrawn from regimen); may decrease serum carbamazepine levels
May decrease contraceptive effects because of induction of microsomal enzymes; menstrual irregularities and pregnancy may occur (alternate birth control suggested); may enhance corticosteroid metabolism by inducing hepatic microsomal enzymes; may increase digitoxin metabolism; may decrease antimicrobial effectiveness of metronidazole; decreases theophylline levels, possibly decreasing effects; may increase clearance and decrease bioavailability of verapamil

Documented hypersensitivity; marked impairment of liver function; severe respiratory disease; nephritis

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

In select patients receiving prolonged therapy, periodic laboratory evaluation of organ (eg, hematopoietic, renal, hepatic systems) may be useful; caution in fever, hyperthyroidism, diabetes mellitus, or severe anemia (adverse reactions possible); caution in myasthenia gravis or myxedema


Oxcarbazepine (Trileptal)

Pharmacologic activity primarily by 10-monohydroxy metabolite (MHD). May block voltage-sensitive sodium channels, inhibit repetitive neuronal firing, and impair synaptic impulse propagation. Anticonvulsant effect may occur by affecting potassium conductance and high-voltage activated calcium channels. Pharmacokinetics similar in children > 8 y and adults. Children <8 y have 30-40% increased clearance. Use in children <2 y not studied in controlled clinical trials.

Adult

Adjunctive therapy
Initial dose: 600 mg/d PO divided bid; may increase by maximum of 600 mg/d qwk; recommended daily dose is 1200 mg/d PO; monitor for adverse effects
Conversion to monotherapy
Initial dose: 600 mg/d PO divided bid; gradually reduce dose of concomitant anticonvulsants over about 3-6 wk, and gradually increase oxcarbazepine dose over 2-4 wk; may increase dose as needed by maximum 600 mg/d PO qwk; closely monitor during transition adverse effects
Initiation of monotherapy
Initial dose: 600 mg/d PO divided bid; increase by 300 mg/d PO q3d to 1200 mg/d; monitor patients for adverse effects

Pediatric

Adjunctive therapy
4-16 years: 8-10 mg/kg/d PO divided bid; not to exceed 600 mg/d; gradually increase to target dose over 2 wk
Target dose based on body weight as follows:
20-29 kg: 900 mg/d PO
29.1-39 kg: 1200 mg/d PO
>39 kg: 1800 mg/d PO

May inhibit CYP2C19 and induce CYP3A4/5; CYPP450 inducers can decrease plasma concentrations of oxcarbazepine and MHD; may decrease levels of dihydropyridine calcium antagonists and oral contraceptives; significant drug interactions related to protein binding unlikely because MHD plasma protein binding low (40%); can reduce serum concentrations of carbamazepine, phenobarbital, phenytoin, and valproic acid; doses >1200 mg/d may increase phenytoin serum concentration by as much as 40% and phenobarbital concentrations by as much as 15%; drugs metabolized by CYP450 enzymes (eg, carbamazepine, phenytoin, phenobarbital) can decrease MHD serum concentration by about 29-40%; can reduce serum concentrations of oral contraceptives and make them ineffective; can increase clearance of felodipine; verapamil may reduce serum MHD levels

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Adverse cognitive effects (eg, psychomotor slowing, impaired concentration, impaired speech, impaired language); in impaired renal function (CrCl <30 mL/min), begin at half usual starting dose and increase increments slowly; can cause hyponatremia ( <125 mmol/L); 25-30% of people with hypersensitivity to carbamazepine hypersensitive to oxcarbazepine; rapid withdrawal can exacerbate seizures (closely observe patient for drug adverse effects, and monitor plasma levels of concomitant anticonvulsants during titration)


Levetiracetam (Keppra)

For adjunctive treatment of partial seizures. Binds to presynaptic vesicle protein (SV2A). Blocks high-voltage calcium currents. Suppresses several negative modulators of GABA and glycine-gated currents.

Adult

500 mg PO bid initially; may increase by 1000 mg/d q2wk; not to exceed 3000 mg/d; reduce dose in reduced renal clearance

Pediatric

<4 years: Not established
4-15 years: 20 mg/kg/d PO divided bid; may increase by 20-mg/kg/d q2wk; not to exceed 60 mg/kg/d; use oral solution if weight <20 kg
>16 years: Administer as in adults

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in renal impairment (reduce dose); major adverse effects include somnolence, asthenia, incoordination, mild leukopenia (3%), and behavioral changes (eg, anxiety, hostility, emotional lability, depression and psychosis [1-2%], depersonalization); seizure frequency may increase following discontinuation (do so gradually); statistically significant decreases in RBCs and WBCs have been observed


Pregabalin (Lyrica)

Binds to the alpha2-delta subunit site of voltage-gated calcium channels) in central nervous system tissues. Modulates calcium channel function and reduces release of multiple neurotransmitters.

Adult

50 mg PO tid initially; increase dose gradually, not to exceed 300 mg/d PO; adjust dose in reduced renal function

Pediatric

Not established

May cause additive effects on cognitive and gross motor functioning when coadministered with drugs that cause dizziness or somnolence

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Discontinue gradually (over a minimum of 1 wk) to minimize increased seizure frequency in patients with seizure disorders; may cause insomnia, nausea, headache, or diarrhea with abrupt withdrawal; common adverse effects include dizziness, somnolence, blurred vision, weight gain, and peripheral edema; may elevate creatinine kinase level, decrease platelet count, and increase PR interval; doses >300 mg/d associated with higher rate of adverse effects and treatment discontinuation; decrease dose with renal impairment (ie, CrCl <60 mL/min)


Zonisamide (Zonegran)

May block sodium channels and reduce voltage-dependent, T-type Ca2+ currents and transient inward currents. Binds to the allosteric GABA/benzodiazepine receptor ionophore. Has weak carbonic anhydrase inhibiting activity.

Adult

100 mg/d PO for 2 wk, then increase by 100 mg/d PO q2wk, not to exceed 400 mg/d; may be given qd or bid

Pediatric

Not established

May increase serum carbamazepine levels; carbamazepine may increase concentrations; phenobarbital may decrease levels

Documented hypersensitivity to sulfonamides or zonisamide

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

May cause drowsiness, weight loss, ataxia, nausea, and slowing of mental activity; pediatric patients have an increased risk for oligohidrosis and hyperthermia

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References
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Further Reading

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Keywords

attacks, convulsions, fainting, spells, impaired consciousness, simple motor automatisms, manual automatisms, oral automatisms, perseverative automatisms, bizarre automatisms, temporal lobe complex partial seizures, parietal lobe seizures, frontal lobe seizures, extratemporal lobe seizures, occipital lobe seizures, complex partial status epilepticus, sudden unexpected death in epilepsy, SUDEP, brain trauma, encephalitis, meningitis, stroke, perinatal brain injuries, vascular malformations, cortical dysplasia, neoplasms, febrile seizures, temporal lobe epilepsy, mesial temporal sclerosis

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Contributor Information and Disclosures

Author

Anthony M Murro, MD, Laboratory Director, Professor, Department of Neurology, Medical College of Georgia
Anthony M Murro, MD is a member of the following medical societies: American Academy of Neurology and American Epilepsy Society
Disclosure: Nothing to disclose.

Medical Editor

Joseph F Hulihan, MD, Vice President, Medical Affairs, Ortho-McNeil Janssen Scientific Affairs, LLC
Joseph F Hulihan, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, American Headache Society, and American Medical Association
Disclosure: Johnson & Johnson Salary Employment; Johnson & Johnson Stock Employment

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
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