Overtreatment in epilepsy: How it occurs and how it can be avoided

CNS Drugs

Volumn 19, Issue 11, 2005, Pages 897-908

  Perucca, Emilio ^a,b   Kwan, Patrick ^c  

^a C MONDINO NATIONAL NEUROLOGICAL INSTITUTE   (Italy)

^b UNIVERSITY OF PAVIA   (Italy)

^c CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

[No Author keywords available]

Indexed keywords

ANTICONVULSIVE AGENT; BENZODIAZEPINE; CARBAMAZEPINE; ETIRACETAM; GABAPENTIN; LAMOTRIGINE; METHYLPHENOBARBITAL; OXCARBAZEPINE; PHENOBARBITAL; PHENYTOIN; PRIMIDONE; TIAGABINE; TOPIRAMATE; VALPROIC ACID; VIGABATRIN; ZONISAMIDE;

BRAIN SURGERY; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL TRIAL; COMORBIDITY; DETERIORATION; DISEASE SEVERITY; DOSE RESPONSE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG COST; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG INTOXICATION; DRUG MEGADOSE; DRUG METABOLISM; DRUG MONITORING; DRUG POTENTIATION; DRUG SAFETY; DRUG TOLERABILITY; DRUG TOLERANCE; EPILEPSY; FOCAL EPILEPSY; GRAND MAL SEIZURE; HEAD INJURY; HEALTH CARE COST; HUMAN; HYPONATREMIA; LONG TERM CARE; LOW DRUG DOSE; MONOTHERAPY; MYOCLONUS; NEUROTOXICITY; POLYPHARMACY; PRESCRIPTION; PRIORITY JOURNAL; PROPHYLAXIS; RASH; REVIEW; RISK BENEFIT ANALYSIS; SIDE EFFECT; TERATOGENICITY; TITRIMETRY; TONIC CLONIC SEIZURE;

ANTICONVULSANTS; EPILEPSY; HUMANS; OVERDOSE; PRESCRIPTIONS, DRUG; RISK; TREATMENT FAILURE;

EID: 27644448562     PISSN: 11727047     EISSN: 11727047     Source Type: Journal    
DOI: 10.2165/00023210-200519110-00001     Document Type: Review

References (97)

1. Sander JW. The epidemiology of epilepsy revisited. Curr Opin Neurol 2003; 16: 165-70
2. Sander JW. The problem of the drug-resistant epilepsies. Novartis Found Symp 2002; 243: 4-12
3. Kwan P, Brodie MJ. Refractory epilepsy: a progressive, intractable but preventable condition? Seizure 2002; 11: 77-84
4. Perucca E, Beghi E, Dulac O, et al. Assessing risk to benefit ratio in antiepileptic drug therapy. Epilepsy Res 2000; 41: 107-39
5. Brodie MJ, Kwan P. Staged approach to epilepsy management. Neurology 2002; 58 (8 Suppl. 5): S2-8
6. Kwan P, Brodie MJ. Neuropsychological effects of epilepsy and antiepileptic drugs. Lancet 2001; 357: 216-22
7. Battino D, Dukes MNG, Perucca E. Anticonvulsants. In: Dukes MNG, Aronson. JK, editors. Meyler's side effects of drugs, 14th ed. Amsterdam: Elsevier Science BV, 2000: 164-97
8. Arroyo S, De La Morena A. Life-threatening adverse events of antiepileptic drugs. Epilepsy Res 2001; 47: 155-74
9. Perucca E. Overtreatment in epilepsy: adverse consequences and mechanisms. Epilepsy Res 2002; 52: 25-33
10. Schmidt D, Elger C, Holmes GL. Pharmacological overtreatment in epilepsy: mechanisms and management. Epilepsy Res 2002; 52: 3-14
11. Smith D, Defalla BA, Chadwick DW. The misdiagnosis of epilepsy and the management of refractory epilepsy in a specialist clinic. Q J Med 1999; 92: 15-23
12. Devinsky O. Patients with refractory seizures. N Engl J Med 1999; 340: 1565-70
13. Kuyk J, Leijten F, Meinardi H, et al. The diagnosis of psychogenic non-epileptic seizures: a review. Seizure 1997; 6: 243-53
14. Schierhout G, Roberts I. Anti-epileptic drugs for preventing seizures following acute traumatic brain injury. Cochrane Database Syst Rev 2001; (4): CD000173
15. Foy PM, Chadwick DW, Rajgopalan N, et al. Do prophylactic anticonvulsant drugs alter the pattern of seizures after craniotomy? J Neurol Neurosurg Psychiatry 1992; 55: 753-7
16. Rosman NP, Colton T, Labazzo J, et al. A controlled trial of diazepam administered during febrile illnesses to prevent recurrence of febrile seizures. N Engl J Med 1993; 329: 79-84
17. Temkin NR, Dikmen SS, Wilensky AJ, et al. A randomized, double-blind study of phenytoin for the prevention of posttraumatic seizures. N Engl J Med 1990; 323: 497-502
18. Temkin NR, Dikmen SS, Anderson GD, et al. Valproate therapy for prevention of posttraumatic seizures: a randomized trial. J Neurosurg 1999; 91: 593-600
19. Temkin NR. Antiepileptogenesis and seizure prevention trials with antiepileptic drugs: metanalysis of controlled trials. Epilepsia 2001; 42: 515-24
20. De Santis A, Villani R, Sinisi M, et al. Add-on phenytoin fails to prevent early seizures after surgery for supratentorial brain tumors: a randomized, controlled study. Epilepsia 2002; 43:175-82
21. Musicco M, Beghi E, Solari A, et al. Treatment of first tonicclonic seizure does not improve the prognosis of epilepsy. First Seizure Trial Group (FIRST Group). Neurology 1997; 49:991-8
22. Manson A, Jacoby A, Johnson A, et al. Immediate versus deferred antiepileptic drug treatment for early epilepsy adn single seizures: a randomized controlled trial. Lancet 2005; 365: 2007-13
23. Beghi E, Perucca E. The management of epilepsy in the 1990s: acquisitions, uncertainties and perspectives for future research. Drugs 1995; 49: 680-94
24. Hauser WA, Rich SS, Annegers JF, et al. Seizure recurrence after a 1st unprovoked seizure: an extended follow-up. Neurology 1990; 40: 1163-70
25. Camfield P, Camfield C. Epileptic syndromes in childhood: clinical features, outcomes, and treatment. Epilepsia 2002; 43 Suppl. 3: 27-32
26. Perucca E, Dulac O, Shorvon S, et al. Harnessing the clinical potential of antiepileptic drug therapy: dosing optimisation. CNS Drugs 2001; 15: 609-12
27. Bateson AN. Basic pharmacologic mechanisms involved in benzodiazepines tolerance and withdrawal. Curr Pharm Des 2002; 8: 5-21
28. Walker MC, Sander JW. Difficulties in extrapolating from clinical trial data to clinical practice: the case of antiepileptic drugs. Neurology 1997; 49: 333-7
29. Stephen LJ, Sills GJ, Brodie MJ. Topiramate in refractory epilepsy: a prospective observational study. Epilepsia 2000;41: 977-80
30. Aldenkamp AP, Baker G, Mulder OG, et al. A multicenter, randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures. Epilepsia 2000; 41: 1167-78
31. Guberman AH, Besag FM, Brodie MJ, et al. Lamotrigine-associated rash: risk/benefit considerations in adults and children. Epilepsia 1999; 40: 985-91
32. Wong IC, Mawer GE, Sander JW. Factors influencing the incidence of lamotrigine-related skin rash. Ann Pharmacother 1999; 33: 1037-42
33. Sullivan JR, Shear NH. The drug hypersensitivity syndrome: what is the pathogenesis? Arch Dermatol 2001; 137: 357-64
34. Perucca E. General principles of medical treatment. In: Shorvon SD, Perucca E, Fish D, et al., editors, The treatment of epilepsy. Oxford: Blackwell Science, 2003: 139-60
35. Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342: 314-9
36. Kwan P, Brodie MJ. Effectiveness of first antiepileptic drug. Epilepsia 2001; 42: 1255-60
37. Privitera MD, Brodie MJ, Mattson RH, et al. Topiramate, carbamazepine and valproate monotherapy: double-blind comparison in newly diagnosed epilepsy. Acta Neurol Scand 2003; 107: 165-75
38. Perucca E, Gram L, Avanzini G, et al. Antiepileptic drugs as a cause of worsening of seizures. Epilepsia 1998; 39: 5-17
39. Richens A, Davidson DLW, Cartlidge NEF, et al. A multicentre comparative trial of sodium valproate and carbamazepine in adult-onset epilepsy. J Neurol Neurosurg Psychiatry 1994; 57: 682-7
40. Schmidt D, Haenel F. Therapeutic plasma levels of phenytoin, phenobarbital, and carbamazepine: individual variation in relation to seizure frequency and type. Neurology 1984; 34: 1252-5
41. Gidal BE, DeCerce J, Bockbrader HN, et al. Gabapentin bioavailability: effect of dose and frequency of administration in adult patients with epilepsy. Epilepsy Res 1998; 31: 91-9
42. Luer MS, Hamani C, Dujovny M, et al. Saturable transport of gabapentin at the blood-brain barrier. Neurol Res 1999; 21: 559-62
43. Wilson EA, Sills GJ, Forrest G, et al. High dose gabapentin in refractory partial epilepsy: clinical observations in 50 patients. Epilepsy Res 1998; 29: 161-6
44. Richens A, Dunlop A. Serum-phenytoin levels in management of epilepsy. Lancet 1975; II: 247-8
45. Elger CE, Bauer J, Scherrmann J, et al. Aggravation of focal epileptic seizures by antiepileptic drugs. Epilepsia 1998; 39 Suppl. 3: S15-8
46. Perucca E. Seizures provoked by antiepileptic drugs and by other medications. Neurologia (Barcelona) 2001; 16 Suppl. 2: 43-51
47. Genton P, Gelisse P, Thomas P, et al. Do carbamazepine and phenytoin aggravate juvenile myoclonic epilepsy? Neurology 2000 Oct 24; 55: 1106-9
48. Guerrini R, Belmonte A, Genton P. Antiepileptic drug-induced worsening of seizures in children. Epilepsia 1998; 39 Suppl. 3: S2-10
49. Somerville ER. Aggravation of partial seizures by antiepileptic drugs: Is there evidence from clinical trials? Neurology 2002; 59: 79-83
50. Willmore LJ. Choice and use of newer anticonvulsant drugs in older patients. Drugs Aging 2000; 17: 441-52
51. Perucca E. The clinical pharmacokinetics of the new antiepileptic drugs. Epilepsia 1999; 40 Suppl. 9: S7-13
52. Zhang C, Glenn DG, Bell WL, et al. Gabapentin-induced myoclonus in end-stage renal disease. Epilepsia 2005 Jan; 46 (1): 156-8
53. Ball S, Borman N. Pharmacogenetics and drug metabolism. Nat Biotech 1998; 16: S4-5
54. Pirmohamed M, Park BK. Genetic susceptibility to adverse drug reactions. Trends Pharmacol Sci 2001; 22: 298-305
55. Caraco Y, Muszkat M, Wood AJ. Phenytoin metabolic ratio: a putative marker of CYP2C9 activity in vivo. Pharmacogenetics 2001; 11: 587-96
56. Van der Weide J, Steijns LS, van Weelden MJ, et al. The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. Pharmacogenetics 2001; 11: 287-91
57. Kidd RS, Curry TB, Gallagher S, et al. Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Pharmacogenetics 2001; 11: 803-8
58. Brandolese R, Scordo MG, Spina E, et al. Severe phenytoin intoxication in a subject homozygous for CYP2C9*3. Clin Pharmacol Ther 2001; 70: 391-4
59. Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med 2005; 352: 2211-21
60. Kupfer A, Branch RA. Stereoselective mephobarbital hydroxylation cosegregates with mephenytoin hydroxylation. Clin Pharmacol Ther 1985; 38: 414-8
61. Mamiya K, Hadama A, Yukawa E, et al. CYP2C19 polymorphism effect on phenobarbitone: pharmacokinetics in Japanese patients with epilepsy: analysis by population pharmacokinetics. Eur J Clin Pharmacol 2000; 55: 821-5
62. Jannuzzi G, Cian P, Fattore C, et al. A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. Epilepsia 2000; 41: 222-30
63. McKee PJW, Brodie MJ. Therapeutic drug monitoring. In: Engel Jr J, Pedley TA, editors. Epilepsy: a comprehensive textbook. Philadelphia (PA): Lippincott-Raven, 1997: 1181-94
64. Johannessen SI, Tomson T. Laboratory monitoring of antiepileptic drugs. In: Levy RH, Mattson RH, Meldrum BS, et al., editors, Antiepileptic drugs. 4th ed. Philadelphia (PA): Lippincott Williams and Wilkins, 2002: 103-11
65. Perucca E. Is there a role for therapeutic drug monitoring of new anticonvulsants? Clin Pharmacokinet 2000; 38: 191-204
66. Woo E, Chan YM, Wu YK, et al. If a well stabilised epileptic patient has a subtherapeutic antiepileptic drug level, should the dose be increased? A randomised prospective study. Epilepsia 1989; 29: 129-39
67. Perucca E, Grimaldi R, Crema A. Interpretation of drug levels in acute and chronic disease states. Clin Pharmacokinet 1985; 10: 498-513
68. Specht U, Elsner H, May TW, et al. Postictal serum levels of antiepileptic drugs for detection of noncompliance. Epilepsy Behav 2003; 4: 487-95
69. Holmes GL. Overtreatment in children with epilepsy. Epilepsy Res 2002; 52: 35-42
70. Deckers C. Overtreatment in adults with epilepsy. Epilepsy Res 2002; 52: 43-52
71. Bourgeois BFD. Reducing overtreatment. Epilepsy Res 2002; 52: 53-60
72. Hakkarainen H. Carbamazepine vs diphenylhydantoin vs their combination in adult epilepsy [abstract]. Neurology 1980; 30: 354
73. Tanganelli P, Regesta G. Vigabatrin vs carbamazepine monotherapy in newly diagnosed focal epilepsy: a randomized response conditional cross-over study. Epilepsy Res 1996; 25: 257-62
74. Walker JE, Koo P. Carbamazepine versus valproate versus combined therapy for refractory partial complex seizures with secondary generalization [abstract]. Epilepsia 1988; 29: 693
75. Schmidt D, Richter K. Alternate single anticonvulsant drug therapy for refractory epilepsy. Ann Neurol 1986; 19: 85-7
76. Kwan P, Brodie MJ. Epilepsy after the first drug fails: substitution or add-on? Seizure 2000; 9: 464-8
77. Stephen LJ, Brodie MJ. Seizure freedom with more than one antiepileptic drug. Seizure 2002; 11 (6): 349-51
78. Deckers CLP, Hekster YA, Keyser A, et al. Monotherapy versus polytherapy for epilepsy: a multicenter double-blind randomized study. Epilepsia 2001; 42: 1387-94
79. Beghi E, Gatti G, Tonini C, et al. Adjunctive therapy versus alternative monotherapy in patients with partial epilepsy failing on a single drug: a multicentre, randomized, pragmatic, controlled trial. Epilepsy Res 2003; 57: 1-13
80. Brodie MJ, Yuen AWC, 105 Study Group. Lamotrigine substitution study: evidence for synergism with sodium valproate. Epilepsy Res 1997; 26: 423-32
81. Pisani F, Oteri G, Russo MF, et al. The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction. Epilepsia 1999; 40: 1141-6
82. Kwan P, Sander JW. Natural history of epilepsy: an epidemiological view. J Neurol Neurosurg Psychiatry. 2004 Oct; 75 (10): 1376-81
83. Perucca E. Pharmacoresistance in epilepsy: how should it be defined? CNS Drugs 1998; 10: 171-9
84. Baldy-Moulinier M, Covanis A, D'Urso C, et al. Therapeutic strategies against epilepsy in Mediterranean countries: a report from an international collaborative survey. Seizure 1998; 7: 513-20
85. Patsalos PN, Froscher W, Pisani F, et al. The importance of drug interactions in epilepsy therapy. Epilepsia 2002; 43: 365-85
86. Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs. Lancet Neurol 2003; 2: 347-56
87. Patsalos PN, Perucca E. Clinically important drug interactions in epilepsy: interactions between antiepileptic drugs and other drugs. Lancet Neurol 2003; 2: 473-81
88. Patel JH, Levy RH, Cutler RE. Phenobarbital-valproic acid interaction in normal man. Clin Pharmacol Ther 1980; 27: 515-21
89. Yuen AWC, Land G, Weatherley B, et al. Sodium valproate inhibits lamotrigine metabolism. Br J Clin Pharmacol 1992; 33: 511-3
90. Besag FMC, Berry DJ, Pool F, et al. Carbamazepine toxicity with lamotrigine: pharmacokinetic or pharmacodynamic interaction? Epilepsia 1998; 39: 183-7
91. Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Elipsoy and Pregnancy Register, Neurol Neurosurg. Psychiatry. Epub 2005 Sep 12
92. Berg AT, Shinnar S. Relapse following discontinuation of antiepileptic drugs: a meta-analysis. Neurology 1994; 44: 601-8
93. Dreifuss FE. Juvenile myoclonic epilepsy: characteristics of a primary generalized epilepsy. Epilepsia 1989; 30 Suppl. 4: S1-7
94. Medical Research Council Antiepileptic Drug Withdrawal Study Group. Prognostic index for recurrence of seizures after remission of epilepsy. BMJ 2003; 306: 1374-8
95. Schmidt D, Baumgartner C, Löscher W. Seizure recurrence after planned discontinuation of antiepileptic drugs in seizure-free patients after epilepsy surgery: a review of current clinical experience. Epilepsia 2004; 45: 179-86
96. Berg AT. Stopping antiepileptic drugs after successful surgery: what do we know? And what do we still need to learn? Epilepsia 2004; 45: 101-2
97. Schmidt D. Strategies to prevent overtreatment with antiepileptic drugs in patients with epilepsy. Epilepsy Res 2002; 52: 61-9