Download PDF
Semin Neurol 2002; 22(3): 309-320
DOI: 10.1055/s-2002-36650
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Epilepsy in the Elderly

Ilo E. Leppik1,2 , Angela Birnbaum3
  • 1MINCEP Epilepsy Care, Minneapolis, Minnesota
  • 2Department of Neurology, University of Minnesota, Minneapolis, Minnesota
  • 3Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota
Further Information

Publication History

Publication Date:
15 January 2003 (online)

    Permissions and Reprints

ABSTRACT

The elderly are the most rapidly growing segment of our population, and onset of epilepsy is higher in this age group than in any other. With advancing age, there are changes in drug absorption, disposition, and binding. In addition, within the elderly are subgroups: (1) elderly healthy except for epilepsy (EH) and (2) elderly with multiple medical problems (EMMP). This review examines the factors that need to be considered when selecting the appropriate antiepileptic drug (AED) for an elderly person with epilepsy. Both the older and newer AEDs are reviewed.

KEYWORD

Elderly - epilepsy - antiepileptic drugs - pharmacokinetics

REFERENCES

  • 1 Hauser W A. Epidemiology of seizures in the elderly. In: Rowan AJ, Ramsay RE, eds. Seizures and Epilepsy in the Elderly Boston: Butterworth-Heinemann 1997: 7-20
    Google Scholar
  • 2 Epilepsy Foundation of America. Epilepsy, a Report to the Nation Landover, MD: Author 1999
  • 3 Cloyd J C, Lackner T E, Leppik I E. Antiepileptics in the elderly. Pharmacoepidemiology and pharmacokinetics.  Arch Fam Med . 1994;  3 589-598
    CrossrefPubMedGoogle Scholar
  • 4 Garrard J, Cloyd J C, Gross C. Factors associated with antiepileptic drug use among nursing home elderly.  J Geriatr Med Sci . 2000;  55 384-392
    PubMedGoogle Scholar
  • 5 Lackner T E, Cloyd J C, Thomas L W, Leppik K E. Antiepileptic drug use in nursing home residents: effect of age, gender, and comedication on patterns of use.  Epilepsia . 1998;  39 1083-1087
    PubMedGoogle Scholar
  • 6 Schachter S S, Cramer G W, Thompson G D, Chaponis R J, Mendelson M A, Lawhorne L. An evaluation of antiepileptic drug therapy in nursing facilities.  J Am Geriatr Soc . 1998;  46 1137-1141
    PubMedGoogle Scholar
  • 7 Dey A N. Characteristics of elderly home health care users; data from the 1994 National Home and Hospice Care Survey.  Adv Data . 1996;  279 1-12
    PubMedGoogle Scholar
  • 8 Leppik I E. Contemporary Diagnosis and Management of the Patient with Epilepsy. 5th ed. Newton, PA: Handbooks in Healthcare 2001
    Google Scholar
  • 9 Hauser W A, Hesdorffer D C. Epilepsy, Frequency, Causes and Consequences.  New York: Demos Publications 1990: 1-51
    Google Scholar
  • 10 Moor S A, Teal T W, eds. Adverse Drug Reaction Surveillance in the Geriatric Population: A Preliminary Review. Proceedings of the Drug Information Association Workshop Geriatric Drug Use: Clinical and Social Perspectives.  Washington, DC: Pergamon Press 1985
    Google Scholar
  • 11 Wallace S M, Verbeeck R K. Plasma protein binding of drugs in the elderly.  Clin Pharmacokinet . 1987;  12 41-72
    PubMedGoogle Scholar
  • 12 Greenblatt D J. Reduced serum albumin concentrations in the elderly: a report from the Boston Collaborative Drug Surveillance Program.  J Am Geriatr Soc . 1979;  27 20-22
    PubMedGoogle Scholar
  • 13 Rowe J W, Andres R, Tobin J D, Norris A H, Shock N W. The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study.  J Gerontol . 1976;  31 155-163
    Google Scholar
  • 14 Verbeeck R K, Cardinal J A, Wallace S M. Effect of age and sex on the plasma binding of acidic and basic drugs.  Eur J Clin Pharmacol . 1984;  27 91-97
    CrossrefPubMedGoogle Scholar
  • 15 Wynne H A, Cope L H, Mutch E, Rawlins M D, Woodhouse K W, James O F. The effect of age on liver volume and apparent liver blood flow in healthy man.  Hepatology . 1989;  9 297-301
    CrossrefPubMedGoogle Scholar
  • 16 Tiula E, Neuvonen P J. Antiepileptic drugs and alpha-1 acid glycoprotein.  N Engl J Med . 1982;  307 1148
    PubMedGoogle Scholar
  • 17 Cusack B J. Drug metabolism in the elderly.  J Clin Pharmacol . 1988;  28 571-576
    PubMedGoogle Scholar
  • 18 Dawling S, Crome P. Clinical pharmacokinetic considerations in the elderly: an update.  Clin Pharmacokinet . 1989;  17 236-263
    PubMedGoogle Scholar
  • 19 Woodhouse K W, Wynne H A. Hepatic drug metabolism and aging.  Br Med Bull . 1988;  15 287-296
    PubMedGoogle Scholar
  • 20 Vestal R E, Norris A H, Tobin J D, Cohen B H, Shock N W, Andres R. Antipyrine metabolism in man: influence of age, alcohol, caffeine and smoking.  Clin Pharmacol Ther . 1975;  18 425-432
    PubMedGoogle Scholar
  • 21 Greenblatt D J, Divoll M, Harmatz J S, Shader R I. Oxazepam kinetics: effects of age and sex.  J Pharmacol Exp Ther . 1980;  215 86-91
    PubMedGoogle Scholar
  • 22 Faich G A, Dreis M, Tomita D. National adverse drug reaction surveillance 1986.  Arch Intern Med . 1988;  148 785-787
    CrossrefPubMedGoogle Scholar
  • 23 Mattson R H, Cramer J A, Collins J F. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures.  N Engl J Med . 1985;  313 145-151
    CrossrefPubMedGoogle Scholar
  • 24 Bauer L A, Blouin R A. Age and phenytoin kinetics in adult epileptics.  Clin Pharmacol Ther . 1982;  31 301-304
    PubMedGoogle Scholar
  • 25 Bach B, Hansen J M, Kampmann J P, Rasmussen S N, Skovsted L. Disposition of antipyrine and phenytoin correlated with age and liver volume in man.  Clin Pharmacokinet . 1981;  6 389-396
    PubMedGoogle Scholar
  • 26 Hayes M J, Langman M JS, Short A H. Changes in drug metabolism with increasing age: II. Phenytoin clearance and protein binding.  Br J Clin Pharmacol . 1975;  2 73-79
    PubMedGoogle Scholar
  • 27 Houghton G W, Richens A, Leighton M. Effects of age, height, weight and sex on serum phenytoin concentrations in epileptic patients.  Br J Clin Pharmacol . 1975;  2 251-256
    PubMedGoogle Scholar
  • 28 Lambie D C, Caird F L. Phenytoin dosage in the elderly.  Age Ageing . 1977;  6 133-137
    PubMedGoogle Scholar
  • 29 Troupin A S, Johannessen S I. Epilepsy in the elderly: a pharmacologic perspective. In: Smith DB, ed. Epilepsy: Current Approaches to Diagnosis and Treatment New York: Raven Press 1990: 141-153
    Google Scholar
  • 30 Mooradian A D, Hernandez L, Tamai I C, Marshall C. Variability of serum phenytoin concentrations in nursing home patients.  Arch Intern Med . 1989;  149 890-892
    CrossrefPubMedGoogle Scholar
  • 31 Nelson M H, Birnbaum A K, Remmel R P. Inhibition of phenytoin hydroxylation in human liver microsomes by several selective serotonin re-uptake inhibitors.  Epilepsy Res . 2001;  44 71-82
    CrossrefPubMedGoogle Scholar
  • 32 Bohannon A D, Hanlon J T, Landerman R, Gold D T. Association of race and other potential risk factors with nonvertebral fractures in community-dwelling elderly women.  Am J Epidemiol . 1999;  149 1002-1009
    PubMedGoogle Scholar
  • 33 Bauer L A, Davis R, Wilensky A. Valproic acid clearance: unbound fraction and diurnal variation in young and elderly adults.  Clin Pharmacol Ther . 1985;  37 697-700
    PubMedGoogle Scholar
  • 34 Bryson S M, Verma N, Scott P JW. Pharmacokinetics of valproic acid in young and elderly subjects.  Br J Clin Pharmacol . 1983;  16 104-105
    PubMedGoogle Scholar
  • 35 Perucca E, Grimaldi R, Gatti G, Pirracchio S, Crema F, Frigo G M. Pharmacokinetics of valproic acid in the elderly.  Br J Clin Pharmacol . 1984;  17 665-669
    PubMedGoogle Scholar
  • 36 Graves N M. Felbamate.  Ann Pharmacother . 1993;  27 1073-1081
    PubMedGoogle Scholar
  • 37 Richens A. Clinical pharmacokinetics of gabapentin. In: Chadwick D, ed. New Trends in Epilepsy Management: The Role of Gabapentin London: Royal Society of Medicine Services 1993: 41-46
    Google Scholar
  • 38 Peck A W. Clinical pharmacology of lamotrigine.  Epilepsia . 1991;  32 (suppl 2) S9-S12
    PubMedGoogle Scholar
  • 39 Posner J, Holdich T, Crome P. Comparison of lamotrigine pharmacokinetics in young and elderly healthy volunteers.  J Pharm Med . 1991;  1 121-128
    PubMedGoogle Scholar
  • 40 Hussein Z, Posner J. Population pharmacokinetics of lamo-trigine monotherapy in patients with epilepsy: retrospective analysis of routine monitoring data.  Br J Clin Pharmacol . 1997;  43 457-465
    CrossrefPubMedGoogle Scholar
  • 41 Yuen A W, Land G, Weatherley B C, Peck A W. Sodium valproate acutely inhibits lamotrigine metabolism.  Br J Clin Pharmacol . 1992;  33 511-513
    CrossrefPubMedGoogle Scholar
  • 42 Sachdeo R C, Sachdeo S K, Walker S A, Kramer L D, Nayak R K, Doose D R. Steady-state pharmacokinetics of topiramate and carbamazepine in patients with epilepsy during monotherapy and concomitant therapy.  Epilepsia . 1996;  37 774-780
    PubMedGoogle Scholar
  • 43 Levy R H, Bishop F, Streeter A J. Explanation and prediction of drug interactions with topiramate using a CYP450 inhibition spectrum. In: Cereghino J, ed. Annual Meeting of the American Epilepsy Society Baltimore: Lippincott-Raven 1995: 47
    Google Scholar
  • 44 Faigle J W, Menge G P. Metabolic characteristics of oxcarbazepine (Trileptal) and their beneficial implications for enzyme induction and drug interactions.  Behav Neurol . 1990;  3 21-30
    PubMedGoogle Scholar
  • 45 van Heiningen N P, Eve M D, Oosterhuis B. The influence of age on the pharmacokinetics of the antiepileptic agent oxcarbazepine.  Clin Pharmacol Ther . 1991;  50 410-419
    PubMedGoogle Scholar
  • 46 Klosterskov J P, Saano V, Harin P, Svenstrup B, Nenge G. Possible interaction between oxcarbazepine and an oral contraceptive.  Epilepsia . 1992;  33 1149-1152
    PubMedGoogle Scholar
  • 47 Zaccara G, Gangemi P F, Bendoni L, Menge G P, Schwabe S, Monza G C. Influence of single and repeated doses of oxcarbazepine on the pharmacokinetic profile of felodipine.  Ther Drug Monit . 1993;  15 39-42
    PubMedGoogle Scholar
  • 48 Hossain M, Sallas W, Gasparini M. Drug-drug interaction profile of oxcarbazepine in children and adults (abstract).  Neurology . 1999;  52 (suppl 2) A525
    PubMedGoogle Scholar
  • 49 Isojarvi J IT, Huuskonen U EJ, Pakarinen A J, Vuolteenaho O, Myllyla V V. The regulation of serum sodium after replacing carbamazepine with oxcarbazepine.  Epilepsia . 2001;  42 741-745
    CrossrefPubMedGoogle Scholar
  • 50 Leppik I E. The place of levetiracetam in the treatment of epilepsy.  Epilepsia . 2001;  42 44-45
    PubMedGoogle Scholar
  • 51 Patsalos P N, Sander J W. Newer antiepileptic drugs. Towards an improved risk-benefit ratio.  Drug Saf . 1994;  11 37-67
    PubMedGoogle Scholar
  • 52 French J. Use of levetiracetam in special populations.  Epilepsia . 2001;  42 40-43
    CrossrefPubMedGoogle Scholar
  • 53 Cook P J, Flanagan R, James I M. Diazepam tolerance: effect of age, regular sedation and alcohol.  Br Med J . 1984;  289 351-353
    PubMedGoogle Scholar
  • 54 Hansten P D, Horn J R. Drug Interactions: A Clinical Perspective and Analysis of Current Developments.  Vancouver, WA: Applied Therapeutics Inc 1993: 331-371
    Google Scholar
  • 55 Nation R L, Evans A M, Milne R W. Pharmacokinetic drug interactions with phenytoin, I, II.  Clin Pharmacokinet . 1990;  18 37-150
    PubMedGoogle Scholar
  • 56 Bollini P, Riva R, Albani F. Decreased phenytoin levels during antineoplastic therapy: a case report.  Epilepsia . 1983;  24 75-78
    PubMedGoogle Scholar
  • 57 Neef C, de Voogd-van den Straaten I. An interaction between cytostatic and anticonvulsant drugs.  Clin Pharmacol Ther . 1988;  43 372-375
    PubMedGoogle Scholar
  • 58 Haley C J, Nelson J. Phenytoin-enteral feeding interaction.  Ann Pharmacother . 1989;  23 796-798
    PubMedGoogle Scholar
  • 59 Sandor P, Sellers E M, Dumbrell M, Khouse V. Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics.  Clin Pharmacol Ther . 1981;  30 390-397
    PubMedGoogle Scholar
  • 60 Cold J A, Wells B G, Froemming J H. Seizure activity associated with antipsychotic therapy.  Ann Pharmacother . 1990;  24 601-606
    PubMedGoogle Scholar
  • 61 Bender A D, Post A, Meier J P, Higson J E, Reichard Jr G. Plasma protein binding of drugs as a function of age in adult human subjects.  J Pharm Sci . 1975;  64 1711-1713
    PubMedGoogle Scholar
  • 62 Drinka P J, Miller J, Voeks S K, Hamel P. Phenytoin binding in a nursing home.  J Geriatr Drug Ther . 1988;  3 73-82
    PubMedGoogle Scholar
  • 63 Eadie M J, Lander C M, Hooper W D, Tyrer J H. Factors influencing plasma phenobarbital levels in epileptic patients.  Br J Clin Pharmacol . 1977;  4 41-47
    PubMedGoogle Scholar
  • 64 Edwards G B, Culberton V L, Anresen G B, Rhodes P J. Free phenytoin concentrations in geriatrics.  J Geriatr Drug Ther . 1988;  3 97-102
    PubMedGoogle Scholar
  • 65 Martines C, Gatti G, Sasso E, Calzetti S, Perucca E. The disposition of primidone in elderly patients.  Br J Clin Pharmacol . 1990;  30 607-611
    CrossrefPubMedGoogle Scholar
  • 66 Morselli P L. Carbamazepine: Absorption, Distribution and Excretion.  Antiepileptic Drugs. 3rd ed. New York: Raven Press 1989: 473-490
    Google Scholar
  • 67 Patterson M, Heazelwood R, Smithhurst B, Eadie M J. Plasma protein binding of phenytoin in the aged: in-vivo studies.  Br J Clin Pharmacol . 1982;  13 423-425
    PubMedGoogle Scholar
  • 68 Sherwin A L, Loynd J S, Bock G W, Sokolowski C D. Effects of age, sex, obesity, and pregnancy on plasma diphenylhydantoin levels.  Epilepsia . 1974;  15 507-521
    PubMedGoogle Scholar
  • 69 Umstead G S, Morales M, McKercher P l. Comparison of total, free, and salivary phenytoin concentrations in geriatric patients.  Clin Pharm . 1986;  5 59-62
    PubMedGoogle Scholar
      >