Management

1. Management • Antiepileptic Drug Therapy • Goal: completely prevent seizures without causing untoward side effects • Treat the underlying conditions • Reverse the problem and prevent its recurrence

2. 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.

3. Drugs of Choice for Adults with Partial Seizure • Phenytoin, carbamazepine, and valproateequally effective in the treatment of both generalized and partial seizures • Phenytoin • Idiosyncratic phenytoin hypersensitivity • similar therapeutic and side-effect profile with valproate • Carbamazepinepreferred as initial drug because of fewer side effects Ropper, Allan, and Robert Brown. Adams and Victor's Principles of Neurology. 8th. McGraw-Hill, 2005.

4. Drug of Choice forElderly 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, ElinorBM, BlaiseBs,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.

5. 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

6. 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

7. 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.

8. 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.

9. Lamotrigine • Lamotrigine • closely resembles phenytoin • less risk of teratogeniceffects • 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.

10. 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.

11. Carbamazepine vs. Lamotrigine

12. 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

13. Post-stroke Maintenance Medications Dipyridamole for Preventing Stroke and Other Vascular Events in Patients With Vascular Disease: An Update (Schryver, Algra and Gijn2008)

15. 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.

16. 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.