Management

• Antiepileptic Drug Therapy– Goal: completely prevent seizures without causing

untoward side effects

• Treat the underlying conditions– Reverse the problem and prevent its recurrence

Medical Management

• Current Perspectives in Epilepsy Treatment: Focus on Monotherapy, 2006– Initial treatment of epilepsy should begin with

AED monotherapy– If initial trial fails, try monotherapy with a second

AED– Combination therapy should be considered only if

the patient fails at least 2 monotherapy trials

Pellock, John, and Michael Privitera. Current Perspectives in Epilepsy Treatment: Focus on Monotherapy. CME Discovery, USA: ArcMesa Educators and Scinexa, LLC., 2006.

Drugs of Choice for Adults with Partial Seizure

Ropper, Allan, and Robert Brown. Adams and Victor's Principles of Neurology. 8th. McGraw-Hill, 2005.

• Phenytoin, carbamazepine, and valproate equally effective in the treatment of both generalized and partial seizures

• Phenytoin– Idiosyncratic phenytoin hypersensitivity– similar therapeutic and side-effect profile with valproate

• Carbamazepine preferred as initial drug because of fewer side effects

Initial Choice Second ChoiceCarbamazepine Valproate

Phenytoin Lamotrigine

Oxcarbazepine

Drug of Choice for Elderly Adults with Partial-Onset Seizures

• ILAE Treatment Guidelines, 2006• Based on available efficacy and effectiveness evidence

alone, LTG and GBP are established as efficacious or effective as initial monotherapy for elderly adults with newly diagnosed or untreated partial-onset seizures (level A)

Glauser, T, Elinor BM, Blaise Bs, et. al. "ILAE Treatment Guidelines: Evidence-based Analysis of Antiepileptic Drug Efficacy and Effectiveness as Initial Monotherapy for Epileptic Seizures and Syndromes." (International League Against Epilepsy) 27, no. 7 (2006): 1094 -1120.

Drug of Choice for Elderly Adults with Partial-Onset Seizures

• ILAE Treatment Guidelines, 2006– Class I Trial• Efficacy: CBZ = LTG and GBP• Effectiveness: LTG and GBP>> CBZ

An International Multicenter Randomized Double-Blind Controlled Trial of Lamotrigine and Sustained-Release Carbamazepine in the Treatment

of Newly Diagnosed Epilepsy in the Elderly (Satre, Erik, et al., 2007)

• P: Patients aged 65 years or older, who had experienced at least two unprovoked partial and/or generalized tonic– clonic seizures

• I: LTG (n = 93) or CBZ (n = 92)– 40-week treatment period: initial 4-week dose

escalation phase and a 36-week maintenance phase

An International Multicenter Randomized Double-Blind Controlled Trial of Lamotrigine and Sustained-Release Carbamazepine in the Treatment

of Newly Diagnosed Epilepsy in the Elderly (Satre, Erik, et al., 2007)

• O: – In the LTG group, 68 patients (73%) completed the 40-

week study period compared with 61 (67%) in the CBZ group

– Higher seizure-free rates for CBZ 46 (75%) than LTG 37 (54%) [OR=0.39, p=0.0129, CI 0.018 to 0.83] in the per-protocol analysis

– Better tolerability for LTG where 13 patients (14%) withdrew due to AEs in the LTG group, compared with 23 (25%) in the CBZ group

• M: Randomized Double-Blind Controlled Trial Saetre, Erik, et al. "An International Multicenter Randomized Double-Blind Controlled Trial of Lamotrigine and Sustained-Release Carbamazepine in the Treatment of Newly Diagnosed Epilepsy in the Elderly." Epilepsia 48.7 (2007): 1292-1302.

Carbamazepine

• Many side effects • Leukopenia is common• Rare instances of pancytopenia,hyponatremia,

and diabetes insipidus as idiosyncratic reactions.

• CBC should be done before treatment – white cell count should be checked regularly

Ropper, Allan, and Robert Brown. Adams and Victor's Principles of Neurology. 8th. McGraw-Hill, 2005.

Lamotrigine

• Lamotrigine– closely resembles phenytoin– less risk of teratogenic effects– selectively blocks the slow sodium channel

prevent release of glutamate and aspartate– effective as a first-line and adjunctive drug for

generalized and focal seizure

Ropper, Allan, and Robert Brown. Adams and Victor's Principles of Neurology. 8th. McGraw-Hill, 2005.

Gabapentin

• chemically similar to GABA• enhances the intrinsic inhibitory system of

GABA in the brain• anticonvulsant mechanism is not known• moderately effective in partial and secondary

generalized seizures • not metabolized by the liver

Ropper, Allan, and Robert Brown. Adams and Victor's Principles of Neurology. 8th. McGraw-Hill, 2005.

Carbamazepine vs. LamotrigineCarbamazepine Lamotrigine

Efficacy CBZ=LTG

Effectiveness CBZ < LTG ✓Tolerability CBZ < LTG ✓CostFrom www.mims.com.ph

Maintenance: 800 mg-1.2 g daily in divided dose or up to 2 g daily

Epazin CR 200mg/tab: Php 20.2/tab x 4 = Php80 daily

Maintenance: 100-200 mg/day once a day or in 2 divided doses

Lamictal 100mg/tab: Php63/tab x 1 = Php63 daily

CBZ <<< LTG

Post-stroke Maintenance Medications

• International Stroke Trial (IST, Lancet 1997;349:1569-1581)– Aspirin treated patients had slightly fewer deaths at 14 days, significantly

fewer recurrent ischemic strokes at 14 days and no excess of hemorrhagic strokes

Post-stroke Maintenance Medications

Dipyridamole for Preventing Stroke and Other Vascular Events in Patients With Vascular Disease: An Update (Schryver, Algra and Gijn 2008)

Discontinuation of Anticonvulsants

• Studies show that the rate of seizure recurrence after AED withdrawal is about two to three times the rate in patients who continue AEDs

• ED discontinuation may be considered in patients whose seizures have been completely controlled for a prolonged period– 1 to 2 years for children & 2 to 5 years for adults

Hixson, John. "Stopping Antiepileptic Drugs." Current Treatment Options in Neurology (Springerlink), 12, no 5 (June 2010): 434-442.

Discontinuation of Anticonvulsants

• Factors such known to increase risk of recurrence• longer duration of epilepsy• an abnormal neurologic examination• an abnormal EEG

– In patients with a favorable prognosis, risk of relapse can be as high as 20% to 25%

– Before withdrawing AEDs, patients should be counseled about their individual risk for relapse and the potential implications of a recurrent seizure, particularly for safety and driving.