ANTIEPILEPTIC DRUGS

                           

1.   Drug Selection

     a.   First correctly diagnose the type of epilepsy you are treating . This
          influences treatment, prognosis and genetic counseling.

     b.   Second, be aware that no prospective, double-blind, cross-over  (or
          randomized) study with sufficient numbers of patients followed
          long-term has been done to define which AED is best for most seizure
          types.

     c.   Use the least expensive AED (all things being equal, like efficacy).

     d.   Use AEDs which can be taken once daily over bid/tid as this improves
          compliance. AEDs almost never need qid dosing (based on half-life or
          side-effects).

     e.   For absence epilepsy (petit mal), ethosuximide (Zarontin) is the AED
          of choice.  Valproate is equally effective--BUT--fatal complications 
          (rare) make it an unacceptable first choice.

     f.   Use valproate for absence plus myoclonic/clonic/tonic/atonic.

     g.   Phenobarbital, primidone, phenytoin and carbamazepine are all equally
          effective against complex partial seizures.

     h.   Valproate, clorazepate are second line drugs for partial seizures.

     i.   Newer is not better, and almost certainly more expensive (Neurontin,
          Lamictal, Topamax, Gabitril)


2.   Monotherapy

     a.   No good study has been done to prove that multiple AED's are
          synergistic in the treatment of epilepsy. Of course, no good study
          says monotherapy is best either.

     b.   Polypharmacy is expensive, increases side effects and increases the
          complexity of adjusting AEDs in the refractory patient.

     c.   Recommend - Start with one AED and push the dose to clinical 
                      toxicity or seizure control.

     d.   Recommend - Withdraw AED's that are not effective.


     e.   Recommend - Arbitrarily never have a patient on more than three (3)
          AED's.

     f.   Recommend - Don't use combinations meds (e.g., Dilantin with
          phenobarbital).

3.   Monitoring

     a.   The quoted "therapeutic" range of blood levels for AED's is a 
          compromise between toxicity and efficacy. In fact, therapeutic means
          seizure control, which does not apply most of the time. If you must
          use blood levels, consider them a TARGET range when first
          instituting treatment.

     b.   AED levels can never substitute for clinical judgment.


     c.   Use AED levels to assess:

          i.   Poor clinical control (compliance, metabolism)

          ii.  Dose-related side effects

          iii. Drug or disease interaction

          iv.  "Routine" levels on controlled, nontoxic patients are not
                indicated.

4.   Guide to Adult Dosing based predominantly on drug half-life.

                             Initial                          Usual
                              Dose        Increment           Maximum
     Primary AED
     -----------
     diphenylhydantoin      300 mg qd   50-100 mg/1-2week      400 mg
     (Dilantin)                              

     phenobarbital           90 mg qd     30 mg/2 wks          180 mg
     (Luminal)

     carbamazepine          200 mg tid   200 mg/3 days        1200 mg
     (Tegretol)

     primidone              250 mg tid    250 mg/2 wks        1500 mg
     (Mysoline)

     ethosuximide           250 mg tid    250 mg/2 wks        1500 mg
     (Zarontin)

     Secondary AED
     -------------
     valproate              250 mg tid    250 mg/3 days        1500 mg
     (Depakote) 

     clorazepate            7.5 mg tid    7.5 mg/3 days          45 mg
     (Tranxene)

     methosuximide          300 mg tid    300 mg/week          1800 mg
     (Celontin)

     clonazepam             0.5 mg tid    0.5 mg/3 days           3 mg
     (Klonopin)

     gabapentin             300 mg tid    300 mg/3 days        3600 mg
     (Neurontin)

     lamotrigine              25 mg qd      25 mg/week          300 mg
     (Lamictal)

     felbamate
     (Felbatol)

     tiagabine                4 mg qd        4 mg/week          32 mg
     (Gabitril)

     topiramate              25 mg qd      25 mg/week          1600 mg
     (Topamax)

5.   Pearls

     a.   Administer two (2) multiple vitamin pills (800 IU vit. D) qd to
          prevent anticonvulsant osteomalacia.

     b.   Use bromides to treat epilepsy in porphyria.



                                REFERENCES

1.   International League Against Epilepsy.  Proposal for Revised Clinical and
     Electroencephalographic Classification of Epileptic Seizures, Epilepsia
     1981;22:489-501.  (Highly recommended.)

2.   Coatsworth, J.J.  Studies on the Clinical Efficacy of Marketed 
     Antiepileptic Drugs, NINDS Monograph No. 12, 1971.

3.   Reynolds, E.H., et al.  Phenytoin Monotherapy for Epilepsy, Epilepsia
     1981;22:475-488.

4.   Olanow, C.W. and Finn, A.L.  Phenytoin,  Pharmacokinetics and Clinical
     Therapeutics, Neurosurgery 1981;8:112-117.  (Required reading
      - illustrates all important principles about ANY AED.)

5.   Woodbury, D.M., Penry, J.K, and Schmidt, R.P.  Antiepileptic Drugs, Raven
     Press, NY, 1972.  (A reference book.)

6.   Beran, R.G., et al.  Doctors' Perspectives of Epilepsy, Epilepsia 
     1981;22:397-406.

7.   Hahn, T.J. and Avioli, L.F.  Anticonvulsant Osteomalacia, Arch Intern Med
     1975;135:997-1000.

8.   Bonkowsky, H.L., et al.  Seizure Management in Acute Hepatic Porphyria,
     Neurology 1980;30:588-592.