CNS Drugs

, Volume 18, Issue 10, pp 617–628 | Cite as

Prescribing Antiepileptic Drugs

Should Patients Be Switched on the Basis of Cost?
Current Opinion

Abstract

To assess the costs of switching from one antiepileptic drug (AED) to another, all associated direct and indirect costs, not only drug acquisition costs, must be considered. The perspective of the healthcare system evaluated in cost-effectiveness analysis is of crucial importance. Multiple clinical factors can influence clinical decisions regarding switching AEDs. The economic cost of poorly controlled epilepsy is enormous and the most cost-effective intervention is an AED that provides total seizure control. Cost-minimisation studies have evaluated costs associated with various medications. If only efficacy and adverse events were considered, then the ‘older’ AEDs were generally more cost effective than the ‘newer’ AEDs. Most studies only examine very specific clinical situations and are not suitable for establishing general clinical recommendations. The pharmacoeconomics of AED choice is highly country specific. While switching to generic formulations is, in general, cost effective, some changes may be detrimental and more costly than remaining on the trade name preparation. For example, as a result of differences in bioavailability and possible loss of seizure control, changing patients to generic phenytoin and carbamazepine can be problematic. Fosphenytoin may only be cost effective in certain clinical situations compared with intravenous phenytoin. Seizure control should not be sacrificed on the basis of costs alone, as the major endpoint in treating epilepsy with AEDs is seizure control without adverse effects. Switching AEDs in clinical practice still depends on the individual clinical situation and choosing AED therapy solely on the basis of initial acquisition costs is unlikely to be cost effective in the long-term care of patients with epilepsy.

References

  1. 1.
    Heaney DC, Sander JWAS. Ensuring appropriate care in epilepsy: an overview of epidemiological and cost of illness considerations. Dis Manag Health Outcomes 1998; 4: 303–13CrossRefGoogle Scholar
  2. 2.
    Begley CE, Famulari M, Annegers JF, et al. The cost of epilepsy in the United States: an estimate from population-based clinical and survey data. Epilepsia 2000; 41(3): 342–51PubMedCrossRefGoogle Scholar
  3. 3.
    Cockerell OC, Hart YM, Sander JW, et al. The cost of epilepsy in the United Kingdom: an estimation based on the results of two population-based studies. Epilepsy Res 1994; 18(3): 249–60PubMedCrossRefGoogle Scholar
  4. 4.
    Berto P, Tinuper P, Viaggi S. Cost-of-illness of epilepsy in Italy: data from a multicentre observational study (Episcreen). Pharmacoeconomics 2000; 17(2): 197–208PubMedCrossRefGoogle Scholar
  5. 5.
    Boon P, D’Have M, Van Walleghem P, et al. Direct medical costs of refractory epilepsy incurred by three different treatment modalities: a prospective assessment. Epilepsia 2002; 43(1): 96–102PubMedCrossRefGoogle Scholar
  6. 6.
    British National Formulary [online]. Available from URL: http://www.bnf.org. [Accessed 2003 Sep]
  7. 7.
    Heaney DC, Shorvon SD, Sander JW, et al. Cost minimization analysis of antiepileptic drugs in newly diagnosed epilepsy in 2 European countries. Epilepsia 2000; 41Suppl. 5: S37–44PubMedGoogle Scholar
  8. 8.
    Daranzi Y, Mikati M. Treatment-refractory epilepsy: an overview of treatment options and costs. Dis Manag Health Outcomes 1997; 2: 111–23CrossRefGoogle Scholar
  9. 9.
    Begley CE, Annegers JF, Lairson DR, et al. Cost of epilepsy in the United States: a model based on incidence and prognosis. Epilepsia 1994; 35(6): 1230–43PubMedCrossRefGoogle Scholar
  10. 10.
    Maltoni S, Messori A. Lifetime cost-utility analysis of patients with refractory epilepsy treated with adjunctive topiramate therapy. Clin Drug Invest 2003; 23(4): 225–32CrossRefGoogle Scholar
  11. 11.
    Selai CE, Smith K, Trimble MR. Adjunctive therapy in epilepsy: a cost-effectiveness comparison of two AEDs. Seizure 1999; 8(1): 8–13PubMedCrossRefGoogle Scholar
  12. 12.
    van Hout B, Gagnon D, McNulty P, et al. The cost effectiveness of two antiepileptic therapies in the absence of direct comparative data. Pharmacoeconomics 2003; 21(5): 315–26PubMedCrossRefGoogle Scholar
  13. 13.
    Levy P. Economic evaluation of antiepileptic drug therapy: a ethodologic review. Epilepsia 2002; 43(5): 550–8PubMedCrossRefGoogle Scholar
  14. 14.
    Weinstein MC, Siegel JE, Gold MR, et al. Recommendations of the panel on cost-effectiveness in health and medicine. JAMA 1996; 276(15): 1253–8PubMedCrossRefGoogle Scholar
  15. 15.
    Shorvon SD. The epidemiology and treatment of chronic and refractory epilepsy. Epilepsia 1996; 37Suppl. 2: S1–3PubMedCrossRefGoogle Scholar
  16. 16.
    Nashef L, Fish DR, Garner S, et al. Sudden death in epilepsy: a study of incidence in a young cohort with epilepsy and learning difficulty. Epilepsia 1995; 36(12): 1187–94PubMedCrossRefGoogle Scholar
  17. 17.
    Sperling MR, Feldman H, Kinman J, et al. Seizure control and mortality in epilepsy. Ann Neurol 1999; 46(1): 45–50PubMedCrossRefGoogle Scholar
  18. 18.
    Wirrell EC, Camfield PR, Camfield CS, et al. Accidental injury is a serious risk in children with typical absence epilepsy. Arch Neurol 1996; 53(9): 929–32PubMedCrossRefGoogle Scholar
  19. 19.
    Jones MW. Consequences of epilepsy: why do we treat seizures? Can J Neurol Sci 1998; 25(4): S24–6PubMedGoogle Scholar
  20. 20.
    Appelton R, Group MRPEI. Seizure-related injuries in children with newly diagnosed epilepsy. Epilepsia 2002; 43: 764–7CrossRefGoogle Scholar
  21. 21.
    Baker GA, Nashef L, van Hout BA. Current issues in the management of epilepsy: the impact of frequent seizures on cost of illness, quality of life, and mortality. Epilepsia 1997; 38Suppl. 1: S1–8PubMedCrossRefGoogle Scholar
  22. 22.
    Baker G, Jacoby A, Buck D, et al. Quality of life of people with epilepsy: a European study. Epilepsia 1997; 38: 353–62PubMedCrossRefGoogle Scholar
  23. 23.
    van Hout B, Gagnon D, Souetre E, et al. Relationship between seizure frequency and costs and quality of life of outpatients with partial epilepsy in France, Germany, and the United Kindgom. Epilepsia 1997; 38(11): 1221–6PubMedCrossRefGoogle Scholar
  24. 24.
    Bourgeois BF, Prensky AL, Palkes HS, et al. Intelligence in epilepsy: aprospective study in children. Ann Neurol 1983; 14(4): 438–44PubMedCrossRefGoogle Scholar
  25. 25.
    Helmstaedter C, Kurthen M, Lux S, et al. Chronic epilepsy and cognition: a longitudinal study in temporal lobe epilepsy. Ann Neurol 2003; 54(4): 425–32PubMedCrossRefGoogle Scholar
  26. 26.
    Hermann BP, Seidenberg M, Bell B. The neurodevelopmental impact of childhood onset temporal lobe epilepsy on brain structure and function and the risk of progressive cognitive effects. Prog Brain Res 2002; 135: 429–38PubMedCrossRefGoogle Scholar
  27. 27.
    Mattson RH, Cramer JA, Collins JF, et al. Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N Engl J Med 1985; 313(3): 145–51PubMedCrossRefGoogle Scholar
  28. 28.
    Mattson RH, Cramer JA, Collins JF. A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group. N Engl J Med 1992; 327(11): 765–71Google Scholar
  29. 29.
    Navarro R, Ashraf T. Cost analysis of carbamazepine, phenytoin, and valproate for the use in complex partial seizures. Med Interface 1993; 6: 113–8Google Scholar
  30. 30.
    Brodie MJ, Richens A, Yuen AW. Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. UK Lamotrigine/Carbamazepine Monotherapy Trial Group. ancet 1995; 345(8948): 476–9Google Scholar
  31. 31.
    Shakespeare A, Simeon G. Economic analysis of epilepsy treatment: a cost minimization analysis comparing carbamazepine and lamotrigine in the UK. Seizure 1998; 7: 119–25PubMedGoogle Scholar
  32. 32.
    Heaney DC, Shorvon SD, Sander JW. An economic appraisal of carbamazepine, lamotrigine, phenytoin and valproate as initial treatment in adults with newly diagnosed epilepsy. Epilepsia 1998; 39Suppl. 3: S19–25PubMedCrossRefGoogle Scholar
  33. 33.
    Lathers CM, Schraeder PL, Claycamp HG. Clinical pharmacology of topiramate versus lamotrigine versus phenobarbital: comparison of efficacy and side effects using odds ratios. J Clin Pharmacol 2003; 43(5): 491–503PubMedGoogle Scholar
  34. 34.
    Vining EP, Mellitis ED, Dorsen MM, et al. Psychologic and behavioral effects of antiepileptic drugs in children: a double-blind comparison between phenobarbital and valproic acid. Pediatrics 1987; 80(2): 165–74PubMedGoogle Scholar
  35. 35.
    Camfield CS, Chaplin S, Doyle AB, et al. Side effects of phenobarbital in toddlers; behavioral and cognitive aspects. J Pediatr 1979; 95(3): 361–5PubMedCrossRefGoogle Scholar
  36. 36.
    de Silva M, MacArdle B, McGowan M, et al. Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy. Lancet 1996; 347(9003): 709–13PubMedCrossRefGoogle Scholar
  37. 37.
    Messori A, Trippoli S, Becagli P, et al. Adjunctive lamotrigine therapy in patients with refractory seizures: a lifetime cost-utility analysis. Eur J Clin Pharmacol 1998; 53(6): 421–7PubMedCrossRefGoogle Scholar
  38. 38.
    O’Neill B, Trimble M, Bloom D. Adjunctive therapy in epilepsy: a cost-effectiveness comparison of alternative treatment options. Seizure 1995; 4: 37–44PubMedCrossRefGoogle Scholar
  39. 39.
    Hughes D, Cockerell OC. A cost minimization study comparing vigabatrin, lamotrigine and gabapentin for the treatment of intractable partial epilepsy. Seizure 1996; 5(2): 89–95PubMedGoogle Scholar
  40. 40.
    Miller P, Millac P. Audit of the management of patients with refractory epilepsy. Seizure 1994; 3(4): 295–9CrossRefGoogle Scholar
  41. 41.
    McLachlan RS, Maher J. Management of antiepileptic drugs following epilepsy surgery: a review. Can J Neurol Sci 2000; 27Suppl. 1: S106–10PubMedGoogle Scholar
  42. 42.
    Wilner AN. Physicians underestimate the frequency of generic carbamazepine substitution: results of a survey and review of the problem. Epilepsy Behav 2002; 3(6): 522–5PubMedCrossRefGoogle Scholar
  43. 43.
    Tyrer JH, Eadie MJ, Sutherland JM, et al. Outbreak of anticonvulsant intoxication in an Australian city. BMJ 1970; 4(730): 271–3PubMedCrossRefGoogle Scholar
  44. 44.
    Besag FM. Is generic prescribing acceptable in epilepsy? Drug Saf 2000; 23(3): 173–82PubMedCrossRefGoogle Scholar
  45. 45.
    Crawford P, Hall WW, Chappell B, et al. Generic prescribing for epilepsy: is it safe? Seizure 1996; 5(1): 1–5PubMedCrossRefGoogle Scholar
  46. 46.
    Rosenbaum DH, Rowan AJ, Tuchman L, et al. Comparative bioavailability of a generic phenytoin and Dilantin. Epilepsia 1994; 35(3): 656–60PubMedCrossRefGoogle Scholar
  47. 47.
    Chen SS, Allen J, Oxley J, et al. Comparative bioavailability of phenytoin from generic formulations in the United Kingdom. Epilepsia 1982; 23(2): 149–52PubMedCrossRefGoogle Scholar
  48. 48.
    Soryal I, Richens A. Bioavailability and dissolution of proprietary and generic formulations of phenytoin. J Neurol Neurosurg Psychiatry 1992; 55(8): 688–91PubMedCrossRefGoogle Scholar
  49. 49.
    Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Assessment: generic substitution for antiepileptic medication. Neurology 1990; 40 (11): 1641–3Google Scholar
  50. 50.
    Welty TE, Pickering PR, Hale BC, et al. Loss of seizure control associated with generic substitution of carbamazepine. Ann Pharmacother 1992; 26(6): 775–7PubMedGoogle Scholar
  51. 51.
    Revankar SN, Desai ND, Bhatt AD, et al. Comparison of absorption rate and bioavailability of two brands of carbamazepine. J Assoc Physicians India 1999; 47(7): 699–702PubMedGoogle Scholar
  52. 52.
    Silpakit O, Amornpichetkoon M, Kaojarern S. Comparative study of bioavailability and clinical efficacy of carbamazepine in epileptic patients. Ann Pharmacother 1997; 31(5): 548–52PubMedGoogle Scholar
  53. 53.
    Oles KS, Penry JK, Smith LD, et al. Therapeutic bioequivalency study of brand name versus generic carbamazepine. Neurology 1992; 42(6): 1147–53PubMedCrossRefGoogle Scholar
  54. 54.
    MacDonald JT. Breakthrough seizure following substitution of Depakene capsules (Abbott) with a generic product. Neurology 1987; 37(12): 1885PubMedCrossRefGoogle Scholar
  55. 55.
    Vadney VJ, Kraushaar KW. Effects of switching from Depakene to generic valproic acid on individuals with mental retardation. Ment Retard 1997; 35(6): 468–72PubMedCrossRefGoogle Scholar
  56. 56.
    Sherwood Brown E, Shellhorn E, Suppes T. Gastrointestinal side-effects after switch to generic valproic acid. Pharmacopsychiatry 1998; 31(3): 114PubMedCrossRefGoogle Scholar
  57. 57.
    DeToledo JC, Ramsay RE. Fosphenytoin and phenytoin in patients with status epilepticus: improved tolerability versus increased costs. Drug Saf 2000; 22(6): 459–66PubMedCrossRefGoogle Scholar
  58. 58.
    Marchetti A, Magar R, Fischer J, et al. A pharmacoeconomic evaluation of intravenous fosphenytoin (Cerebyx) versus intravenous henytoin (Dilantin) in hospital emergency departments. Clin Ther 1996; 18(5): 953–66PubMedCrossRefGoogle Scholar
  59. 59.
    Touchette DR, Rhoney DH. Cost-minimization analysis of phenytoin and fosphenytoin in the emergency department. Pharmacotherapy 2000; 20(8): 908–16PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  1. 1.Neuroscience Center at Dartmouth, Section of NeurologyDartmouth Medical SchoolHanoverUSA
  2. 2.Section of NeurologyDartmouth-Hitchcock Medical CenterLebanonUSA

Personalised recommendations