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Neuropsychological and Behavioral Effects of Antiepilepsy Drugs

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Abstract

Antiepilepsy drugs work by decreasing neuronal irritability, which may also result in the non-desired side effect of decreased neuropsychological function. In addition to cognitive side effects, antiepilepsy drugs (AEDs) may be associated with behavioral effects which may range from irritability and hyperactivity to positive psychotropic effects on mood. There have been many new medications released since the 1990s, and although they tend to have more favorable side effect profiles compared to their older counterparts, there continues to be a risk of decreased cognitive function with the majority of these agents. The effects of in utero antiepilepsy drug exposure are increasingly being investigated, and differential drug risk is beginning to be described for both anatomic and cognitive outcomes. Patients with epilepsy undergoing neuropsychological evaluations are commonly on AEDs, and it is important for the clinician to recognize the potential contribution of AED therapy to neuropsychological profiles. The present article serves to provide an overview of our current understanding regarding the risks of antiepilepsy drug use for both cognitive and behavioral side effects.

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References

  • Adab, N., Jacoby, A., Smith, D., & Chadwick, D. (2001). Additional educational needs in children born to mothers with epilepsy. Journal of Neurology, Neurosurgery & Psychiatry, 70, 15–21.

    Article  CAS  Google Scholar 

  • Adab, N., Kini, U., Vinten, J., Ayres, J., Baker, G., & Clayton-Smith, J., et al. (2004). The longer term outcome of children born to mothers with epilepsy. Journal of Neurology, Neurosurgery & Psychiatry, 75(11), 1575–1583.

    Article  CAS  Google Scholar 

  • Adams, J., Vorhees, C. V., & Middaugh, L. D. (1990). Developmental neurotoxicity of anticonvulsants: Human and animal evidence on phenytoin. Neurotoxicology & Teratology, 12(3), 203–214.

    Article  CAS  Google Scholar 

  • Aikia, M., Jutila, L., Salmenpera, T., Mervaala, E., & Kalviainen, R. (2006a). Comparison of the Cognitive effects of tiagabine and carbamazepine as monotherapy in newly diagnosed adult patients with partial epilepsy: Pooled analysis of two long-term, randomized, follow-up studies. Epilepsia, 47(7), 1121–1127.

    Article  PubMed  CAS  Google Scholar 

  • Aikia, M., Jutila, L., Salmenpera, T., Mervaala, E., & Kalviainen, R. (2006b). Long-term effects of tiagabine monotherapy on cognition and mood in adult patients with chronic partial epilepsy. Epilepsy & Behavior, 8(4), 750–755.

    Article  Google Scholar 

  • Aikia, M., Kalviainen, R., Sivenius, J., Halonen, T., & Riekkinen, P. J. (1992). Cognitive effects of oxcarbazepine and phenytoin monotherapy in newly diagnosed epilepsy: One year follow-up. Epilepsy Research, 11(3), 199–203.

    Article  PubMed  CAS  Google Scholar 

  • Aldenkamp, A. P., Arends, J., Bootsma, H. P., Diepman, L., Hulsman, J., & Lambrechts, D., et al. (2002). Randomized double-blind parallel-group study comparing cognitive effects of a low-dose lamotrigine with valproate and placebo in healthy volunteers. Epilepsia, 43(1), 19–26.

    Article  PubMed  CAS  Google Scholar 

  • Aldenkamp, A. P., Baker, G., Mulder, O. G., Chadwick, D., Cooper, P., & Doelman, J., et al. (2000). 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, 41(9), 1167–1178.

    Article  PubMed  CAS  Google Scholar 

  • Aldenkamp, A. P., Dreifuss, F. E., Renier, W. O., & Suumeijer, P. B. M. (1995). Epilepsy in children and adolescents. Boca Raton, FL: CRC Press.

    Google Scholar 

  • Anonymous (1992). Correction. New England Journal of Medicine, 326, 144.

    Article  Google Scholar 

  • Artama, M., Auvinen, A., Raudaskoski, T., Isojarvi, I., & Isojarvi, J. (2005). Antiepileptic drug use of women with epilepsy and congenital malformations in offspring. Neurology, 64(11), 1874–1878.

    Article  PubMed  CAS  Google Scholar 

  • Berent, S., Sackellares, J. C., Giordani, B., Wagner, J. G., Donofrio, P. D., & Abou-Khalil, B. (1987). Zonisamide (CI-912) and cognition: Results from preliminary study. Epilepsia, 28(1), 61–67.

    Article  PubMed  CAS  Google Scholar 

  • Bittigau, P., Sifringer, M., & Ikonomidou, C. (2003a). Antiepileptic drugs and apoptosis in the developing brain. Annals of the New York Academy of Sciences, 993, 103–114.

    PubMed  CAS  Google Scholar 

  • Bittigau, P., Sifringer, M., & Ikonomidou, C. (2003b). Antiepileptic drugs and apoptosis in the developing brain. Annals of the New York Academy of Sciences, 993(1), 103–114.

    PubMed  CAS  Google Scholar 

  • Blum, D., Meador, K., Biton, V., Fakhoury, T., Shneker, B., & Chung, S., et al. (2006). Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy. Neurology, 67(3), 400–406.

    Article  PubMed  CAS  Google Scholar 

  • Bootsma, H. P. R., Ricker, L., Diepman, L., Gehring, J., Hulsman, J., Lambrechts, D., et al. (2007). Long-term effects of levetiracetam and topiramate in clinical practice: A head-to-head comparison. Seizure, In Press, Corrected Proof.

  • Brodie, M. J., Richens, A., & Yuen, A. W. (1995). Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. UK lamotrigine/carbamazepine monotherapy trial group. Lancet, 345(8948), 476–479.

    Article  PubMed  CAS  Google Scholar 

  • Buchanan, N. (1995). The efficacy of lamotrigine on seizure control in 34 children, adolescents and young adults with intellectual and physical disability. Seizure, 4(3), 233–236.

    Article  PubMed  CAS  Google Scholar 

  • Carpay, J. A., Aldenkamp, A. P., & van Donselaar, C. A. (2005). Complaints associated with the use of antiepileptic drugs: results from a community-based study. Seizure, 14(3), 198–206.

    Article  PubMed  CAS  Google Scholar 

  • Chadwick, D., Anhut, H., Greiner, M., Alexander, J., Murray, G., & Garofalo, E., et al. (1998). A double-blind trial of gabapentin monotherapy for newly diagnosed partial seizures. International Gabapentin Monotherapy Study Group 945-77. Neurology, 51(5), 1282–1288.

    PubMed  CAS  Google Scholar 

  • Chen, Y., Chi Chow, J., & Lee, I. (2001). Comparison the cognitive effect of anti-epileptic drugs in seizure-free children with epilepsy before and after drug withdrawal. Epilepsy Research, 44(1), 65–70.

    Article  PubMed  CAS  Google Scholar 

  • Cohen, A. F., Ashby, L., Crowley, D., Land, G., Peck, A. W., & Miller, A. A. (1985). Lamotrigine (BW430C), a potential anticonvulsant. Effects on the central nervous system in comparison with phenytoin and diazepam. British Journal of Clinical Pharmacology, 20(6), 619–629.

    PubMed  CAS  Google Scholar 

  • Cramer, J. A., De Rue, K., Devinsky, O., Edrich, P., & Trimble, M. R. (2003). A systematic review of the behavioral effects of levetiracetam in adults with epilepsy, cognitive disorders, or an anxiety disorder during clinical trials. Epilepsy and Behavior, 4(2), 124–132.

    Article  PubMed  Google Scholar 

  • Cumming, R. G., & Le Couteur, D. G. (2003). Benzodiazepines and risk of hip fractures in older people: a review of the evidence. CNS Drugs, 17(11), 825–837.

    Article  PubMed  CAS  Google Scholar 

  • Cunnington, M., & Tennis, P. (2005). Lamotrigine and the risk of malformations in pregnancy. Neurology, 64(6), 955–960.

    PubMed  CAS  Google Scholar 

  • Curran, H. V., & Java, R. (1993). Memory and psychomotor effects of oxcarbazepine in healthy human volunteers. European Journal of Clinical Pharmacology, 44(6), 529–533.

    Article  PubMed  CAS  Google Scholar 

  • Dodrill, C. B., Arnett, J. L., Deaton, R., Lenz, G. T., & Sommerville, K. W. (2000). Tiagabine versus phenytoin and carbamazepine as add-on therapies: Effects on abilities, adjustment, and mood. Epilepsy Research, 42(2–3), 123–132.

    Article  PubMed  CAS  Google Scholar 

  • Dodrill, C. B., Arnett, J. L., Hayes, A. G., Garofalo, E. A., Greeley, C. A., & Greiner, M. J., et al. (1999). Cognitive abilities and adjustment with gabapentin: Results of a multisite study. Epilepsy Research, 35(2), 109–121.

    Article  PubMed  CAS  Google Scholar 

  • Dodrill, C. B., Arnett, J. L., Sommerville, K. W., & Shu, V. (1997). Cognitive and quality of life effects of differing dosages of tiagabine in epilepsy. Neurology, 48(4), 1025–1031.

    PubMed  CAS  Google Scholar 

  • Dodrill, C. B., Arnett, J. L., Sommerville, K. W., & Sussman, N. M. (1993). Evaluation of the effects of vigabatrin on cognitive abilities and quality of life in epilepsy. Neurology, 43(12), 2501–2507.

    PubMed  CAS  Google Scholar 

  • Dodrill, C. B., Arnett, J. L., Sommerville, K. W., & Sussman, N. M. (1995). Effects of differing dosages of vigabatrin (Sabril) on cognitive abilities and quality of life in epilepsy. Epilepsia, 36(2), 164–173.

    Article  PubMed  CAS  Google Scholar 

  • Dodrill, C. B., & Troupin, A. S. (1991). Neuropsychological effects of carbamazepine and phenytoin: A reanalysis. Neurology, 41(1), 141–143.

    PubMed  CAS  Google Scholar 

  • Donati, F., Gobbi, G., Campistol, J., Rapatz, G., Daehler, M., & Sturm, Y., et al. (2006). Effects of oxcarbazepine on cognitive function in children and adolescents with partial seizures. Neurology, 67(4), 679−682.

    Article  PubMed  CAS  Google Scholar 

  • Donati, F., Gobbi, G., Campistol, J., Rapatz, G., Daehler, M., Sturm, Y., et al. (2007). The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures. Seizure, In Press, Corrected Proof.

  • Farwell, J. R., Lee, Y. J., Hirtz, D. G., Sulzbacher, S. I., Ellenberg, J. H., & Nelson, K. B. (1990). Phenobarbital for febrile seizures–effects on intelligence and on seizure recurrence. New England Journal of Medicine, 322(6), 364–369.

    Article  PubMed  CAS  Google Scholar 

  • Ferrie, C. D., Robinson, R. O., & Panayiotopoulos, C. P. (1996). Psychotic and severe behavioural reactions with vigabatrin: A review. Acta Neurologica Scandinavica, 93(1), 1–8.

    PubMed  CAS  Google Scholar 

  • Finnell, R. H., & Dansky, L. V. (1991). Parental epilepsy, anticonvulsant drugs, and reproductive outcome: Epidemiologic and experimental findings spanning three decades; 1: Animal studies. Reproductive Toxicology, 5(4), 281–299.

    Article  PubMed  CAS  Google Scholar 

  • Fisher, J. E., & Vorhees, C. V. (1992). Developmental toxicity of antiepileptic drugs: Relationship to postnatal dysfunction. Pharmacological Research, 26(3), 207–221.

    Article  PubMed  CAS  Google Scholar 

  • Fritz, N., Glogau, S., Hoffmann, J., Rademacher, M., Elger, C. E., & Helmstaedter, C. (2005). Efficacy and cognitive side effects of tiagabine and topiramate in patients with epilepsy. Epilepsy & Behavior, 6(3), 373–381.

    Article  CAS  Google Scholar 

  • Gaily, E., Kantola-Sorsa, E., Hiilesmaa, V., Isoaho, M., Matila, R., & Kotila, M., et al. (2004). Normal intelligence in children with prenatal exposure to carbamazepine. Neurology, 62(1), 28–32.

    PubMed  CAS  Google Scholar 

  • Garrard, J., Harms, S., Eberly, L.E., Leppik, I. E. (2007). In J. C. C. R. E. Ramsay, K. M. Kelly, I. E. Leppik, E. Perucca, & (Eds.) The neurobiology of epilepsy and aging Use of antiepileptic medications in nursing homes international review of neurobiology (vol. 81, pp. 165–182). San Diego: Academic.

    Chapter  Google Scholar 

  • Garrard, J., Harms, S., Hardie, N., Eberly, L. E., Nitz, N., & Bland, P., et al. (2003). Antiepileptic drug use in nursing home admissions. Annals of Neurology, 54(1), 75–85.

    Article  PubMed  Google Scholar 

  • Gilliam, F. (2002). Optimizing health outcomes in active epilepsy. Neurology, 58(8 Suppl 5), S9–S20.

    PubMed  Google Scholar 

  • Gillham, R., Baker, G., Thompson, P., Birbeck, K., McGuire, A., & Tomlinson, L., et al. (1996). Standardisation of a self-report questionnaire for use in evaluating cognitive, affective and behavioural side-effects of anti-epileptic drug treatments. Epilepsy Research, 24(1), 47–55.

    Article  PubMed  CAS  Google Scholar 

  • Gillham, R. A., Blacklaw, J., McKee, P. J., & Brodie, M. J. (1993). Effect of vigabatrin on sedation and cognitive function in patients with refractory epilepsy. Journal of Neurology, Neurosurgery & Psychiatry, 56(12), 1271–1275.

    Article  CAS  Google Scholar 

  • Glauser, T. A. (2004). Behavioral and psychiatric adverse events associated with antiepileptic drugs commonly used in pediatric patients. Journal of Child Neurology, 19, S25–S38.

    Article  PubMed  Google Scholar 

  • Glauser, T. A., Gauer, L. J., Chen, L., & Group, L. N. P. S. (2004). Multicenter, double-blind, placebo-controlled trial of adjunctive levetiracetam (Keppra ®) therapy (up to 60 mg/kg/day) in pediatric patients with refractory partial epilepsy. Epilepsia, 45(Suppl 7), 186.

    Google Scholar 

  • Glier, C., Dzietko, M., Bittigau, P., Jarosz, B., Korobowicz, E., & Ikonomidou, C. (2004). Therapeutic doses of topiramate are not toxic to the developing rat brain. Experimental Neurology, 187(2), 403–409.

    Article  PubMed  CAS  Google Scholar 

  • Gomer, B., Wagner, K., Frings, L., Saar, J., Carius, A., & Harle, M., et al. (2007). The influence of antiepileptic drugs on cognition: A comparison of levetiracetam with topiramate. Epilepsy & Behavior, 10(3), 486–494.

    Article  Google Scholar 

  • Gross-Tsur, V., & Shalev, R. S. (2004). Reversible language regression as an adverse effect of topiramate treatment in children. Neurology, 62(2), 299–300.

    PubMed  Google Scholar 

  • Grunewald, R. A., Thompson, P. J., Corcoran, R., Corden, Z., Jackson, G. D., & Duncan, J. S. (1994). Effects of vigabatrin on partial seizures and cognitive function. Journal of Neurology, Neurosurgery & Psychiatry, 57(9), 1057–1063.

    CAS  Google Scholar 

  • Hamilton, M. J., Cohen, A. F., Yuen, A. W., Harkin, N., Land, G., & Weatherley, B. C., et al. (1993). Carbamazepine and lamotrigine in healthy volunteers: Relevance to early tolerance and clinical trial dosage. Epilepsia, 34(1), 166–173.

    Article  PubMed  CAS  Google Scholar 

  • Herranz, J. L., Armijo, J. A., & Arteaga, R. (1988). Clinical side effects of phenobarbital, primidone, phenytoin, carbamazepine, and valproate during monotherapy in children. Epilepsia, 29(6), 794–804.

    Article  PubMed  CAS  Google Scholar 

  • Hindmarch, I., Trick, L., & Ridout, F. (2005). A double-blind, placebo- and positive-internal-controlled (alprazolam) investigation of the cognitive and psychomotor profile of pregabalin in healthy volunteers. Psychopharmacology, 183(2), 133–143.

    Article  PubMed  CAS  Google Scholar 

  • Kalviainen, R., Aikia, M., Mervaala, E., Saukkonen, A. M., Pitkanen, A., & Riekkinen Sr., P. J. (1996). Long-term cognitive and EEG effects of tiagabine in drug-resistant partial epilepsy. Epilepsy Research, 25(3), 291–297.

    Article  PubMed  CAS  Google Scholar 

  • Kalviainen, R., Aikia, M., Saukkonen, A. M., Mervaala, E., & Riekkinen, P. J. S. (1995). Vigabatrin vs carbamazepine monotherapy in patients with newly diagnosed epilepsy. A randomized, controlled study. Archives of Neurology, 52(10), 989–996.

    PubMed  CAS  Google Scholar 

  • Katz, I., Kim, J., Gale, K., & Kondratyev, A. (2006). Effects of lamotrigine on apoptotic cell death in the neonatal rat brain. http://aesnet.org/Visitors/AnnualMeeting/Abstracts/dsp_Abstract.cfm?id=6623.

  • Kim, J., Kondratyev, A., & Gale, K. (2006). Enhancement of phenytoin-induced neuronal death in neonatal rats by AEDs that do not induce neuronal death when given alone. http://aesnet.org/Visitors/AnnualMeeting/Abstracts/dsp_Abstract.cfm?id=6621.

  • Kim, J., Lapides, D., Kondratyev, A., & Gale, K. (2004). Repeated brief seizures in neonatal rats attenuates programmed cell death induced by MK-801. Epilepsia, 45(Suppl 7), 209.

    Google Scholar 

  • Kockelmann, E., Elger, C. E., & Helmstaedter, C. (2003). Significant improvement in frontal lobe associated neuropsychological functions after withdrawal of Topiramate in epilepsy patients. Epilepsy Research, 54(2–3), 171–178.

    Article  PubMed  CAS  Google Scholar 

  • Kossoff, E. H., Bergey, G. K., Freeman, J. M., & Vining, E. P. (2001). Levetiracetam psychosis in children with epilepsy. Epilepsia, 42(12), 1611–1613.

    Article  PubMed  CAS  Google Scholar 

  • Kwan, P., & Brodie, M. J. (2001a). Effectiveness of first antiepileptic drug. Epilepsia, 42(10), 1255–1260.

    Article  PubMed  CAS  Google Scholar 

  • Kwan, P., & Brodie, M. J. (2001b). Neuropsychological effects of epilepsy and antiepileptic drugs. Lancet, 357(9251), 216–222.

    Article  PubMed  CAS  Google Scholar 

  • Lackner, T. E., Cloyd, J. C., Thomas, L. W., & Leppik, I. E. (1998). Antiepileptic drug use in nursing home residents: Effect of age, gender, and comedication on patterns of use. Epilepsia, 39(10), 1083–1087.

    Article  PubMed  CAS  Google Scholar 

  • Leach, J. P., Girvan, J., Paul, A., & Brodie, M. J. (1997). Gabapentin and cognition: a double blind, dose ranging, placebo controlled study in refractory epilepsy. Journal of Neurology, Neurosurgery & Psychiatry, 62(4), 372–376.

    CAS  Google Scholar 

  • Leach, M. J., Marden, C. M., & Miller, A. A. (1986). Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action. Epilepsia, 27(5), 490–497.

    Article  PubMed  CAS  Google Scholar 

  • Lee, H.-W., Jung, D.-K., Suh, C.-K., Kwon, S.-H., & Park, S.-P. (2006). Cognitive effects of low-dose topiramate monotherapy in epilepsy patients: A 1-year follow-up. Epilepsy & Behavior, 8(4), 736–741.

    Article  Google Scholar 

  • Lee, D. O., Steingard, R. J., Cesena, M., Helmers, S. L., Riviello, J. J., & Mikati, M. A. (1996). Behavioral side effects of gabapentin in children. Epilepsia, 37(1), 87–90.

    Article  PubMed  CAS  Google Scholar 

  • Lee, S., Sziklas, V., Andermann, F., Farnham, S., Risse, G., & Gustafson, M., et al. (2003). The effects of adjunctive topiramate on cognitive function in patients with epilepsy. Epilepsia, 44(3), 339–347.

    Article  PubMed  CAS  Google Scholar 

  • Lennox, W. G. (1942). Brain injury, drugs and environment as causes of mental decay in epilepsy. American Journal of Psychiatry, 99, 174–180.

    Google Scholar 

  • Loring, D. W., & Meador, K. J. (2004). Cognitive side effects of antiepileptic drugs in children. Neurology, 62, 872–877.

    PubMed  CAS  Google Scholar 

  • Loring, D. W., Meador, K. J., Williamson, D. J., Wiegand, F., & Hulihan, J. (2007). Topiramate dose effects on neuropsychological function: Analysis from a randomized double-blind placebo-controlled study. Paper presented at the annual meeting of the American Epilepsy Society, Philadelphia, PA, December.

  • Mackay, F. J., Wilton, L. V., Pearce, G. L., Freemantle, S. N., & Mann, R. D. (1997). Safety of long-term lamotrigine in epilepsy. Epilepsia, 38(8), 881–886.

    Article  PubMed  CAS  Google Scholar 

  • Manthey, D., Asimiadou, S., Stefovska, V., Kaindl, A. M., Fassbender, J., & Ikonomidou, C., et al. (2005). Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat brain. Experimental Neurology, 193(2), 497–503.

    Article  PubMed  CAS  Google Scholar 

  • Marson, A. G., Al-Kharusi, A. M., Alwaidh, M., Appleton, R., Baker, G. A., & Chadwick, D. W., et al. (2007). The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: An unblinded randomised controlled trial. The Lancet, 369(9566), 1016–1026.

    Article  CAS  Google Scholar 

  • Martin, R., Kuzniecky, R., Ho, S., Hetherington, H., Pan, J., & Sinclair, K., et al. (1999). Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology, 52(2), 321–327.

    PubMed  CAS  Google Scholar 

  • Martin, R., Meador, K., Turrentine, L., Faught, E., Sinclair, K., & Kuzniecky, R., et al. (2001). Comparative cognitive effects of carbamazepine and gabapentin in healthy senior adults. Epilepsia, 42(6), 764–771.

    Article  PubMed  CAS  Google Scholar 

  • Mattson, R., Cramer, J., Collins, J., Smith, D., Delgado-Escueta, A., & Browne, T., et al. (1985). Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. New England Journal of Medicine, 313(3), 145–151.

    Article  PubMed  CAS  Google Scholar 

  • Meador, K. J. (2005). Cognitive effects of epilepsy and of antiepileptic medications. In E. Wyllie (Ed.) The treatment of epilepsy ((pp. 1215–1226)4th ed.). Baltimore, M.D.: Williams & Wilkins.

    Google Scholar 

  • Meador, K. J., & Baker, G. A. (1997). Behavioral and cognitive effects of lamotrigine. Journal of Child Neurology, 12(Suppl 1), S44–S47.

    Article  PubMed  Google Scholar 

  • Meador, K. J., Baker, G. A., Finnell, R. H., Kalayjian, L. A., Liporace, J. D., & Loring, D. W., et al. (2006). In utero antiepileptic drug exposure: Fetal death and malformations. Neurology, 67(3), 407–412.

    Article  PubMed  CAS  Google Scholar 

  • Meador, K. J., Browning, N., Cohen, M. J., Kalayjian, L. A., Liporace, J., & Pennell, P. B., et al. (2007a). Cognitive outcomes at 2 years old in children of women with epilepsy differ as function of in utero antiepileptic drug. Neurology, 68(Suppl 1), A337.

    Google Scholar 

  • Meador, K. J., Gevins, A., Loring, D. W., McEvoy, L. K., Ray, P. G., Smith, M. E., et al. (2007b). Neuropsychological and neurophysiological effects of carbamazepine and levetiracetam. Neurology, in press.

  • Meador, K. J., Loring, D. W., Abney, O. L., Allen, M. E., Moore, E. E., & Zamrini, E. Y., et al. (1993). Effects of carbamazepine and phenytoin on EEG and memory in healthy adults. Epilepsia, 34(1), 153–157.

    Article  PubMed  CAS  Google Scholar 

  • Meador, K. J., Loring, D. W., Allen, M. E., Zamrini, E. Y., Moore, E. E., & Abney, O. L., et al. (1991). Comparative cognitive effects of carbamazepine and phenytoin in healthy adults. Neurology, 41(10), 1537–1540.

    PubMed  CAS  Google Scholar 

  • Meador, K. J., Loring, D. W., Huh, K., Gallagher, B. B., & King, D. W. (1990). Comparative cognitive effects of anticonvulsants. Neurology, 40(3 Pt 1), 391–394.

    PubMed  CAS  Google Scholar 

  • Meador, K. J., Loring, D. W., Hulihan, J. F., Kamin, M., & Karim, R. (2003). Differential cognitive and behavioral effects of topiramate and valproate. Neurology, 60(9), 1483–1488.

    PubMed  CAS  Google Scholar 

  • Meador, K. J., Loring, D. W., Moore, E. E., Thompson, W. O., Nichols, M. E., & Oberzan, R. E., et al. (1995). Comparative cognitive effects of phenobarbital, phenytoin, and valproate in healthy adults. Neurology, 45(8), 1494–1499.

    PubMed  CAS  Google Scholar 

  • Meador, K. J., Loring, D. W., Ray, P. G., Murro, A. M., King, D. W., & Nichols, M. E., et al. (1999). Differential cognitive effects of carbamazepine and gabapentin. Epilepsia, 40(9), 1279–1285.

    Article  PubMed  CAS  Google Scholar 

  • Meador, K. J., Loring, D. W., Ray, P. G., Murro, A. M., King, D. W., & Perrine, K. R., et al. (2001). Differential cognitive and behavioral effects of carbamazepine and lamotrigine. Neurology, 56, 1177–1182.

    PubMed  CAS  Google Scholar 

  • Meador, K. J., Loring, D. W., Vahle, V. J., Ray, P. G., Werz, M. A., & Fessler, A. J., et al. (2005). Cognitive and behavioral effects of lamotrigine and topiramate in healthy volunteers. Neurology, 64(12), 2108–2114.

    Article  PubMed  CAS  Google Scholar 

  • Mecarelli, O., Vicenzini, E., Pulitano, P., Vanacore, N., Romolo, F. S., & Di Piero, V., et al. (2004). Clinical, cognitive, and neurophysiologic correlates of short-term treatment with carbamazepine, oxcarbazepine, and levetiracetam in healthy volunteers. Annals of Pharmacotherapy, 38(11), 1816–1822.

    Article  PubMed  CAS  Google Scholar 

  • Miller, N. R., Johnson, M. A., Paul, S. R., Girkin, C. A., Perry, J. D., & Endres, M., et al. (1999). Visual dysfunction in patients receiving vigabatrin: Clinical and electrophysiologic findings. Neurology, 53(9), 2082.

    PubMed  CAS  Google Scholar 

  • Mortimore, C., Trimble, M., & Emmers, E. (1998). Effects of gabapentin on cognition and quality of life in patients with epilepsy. Seizure, 7(5), 359–364.

    Article  PubMed  CAS  Google Scholar 

  • Mula, M., Trimble, M. R., Lhatoo, S. D., & Sander, J. W. A. S. (2003). Topiramate and psychiatric adverse events in patients with epilepsy. Epilepsia, 44(5), 659–663.

    Article  PubMed  Google Scholar 

  • Neyens, L. G., Alpherts, W. C., & Aldenkamp, A. P. (1995). Cognitive effects of a new pyrrolidine derivative (levetiracetam) in patients with epilepsy. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 19(3), 411–419.

    Article  CAS  Google Scholar 

  • Pellock, J. M., Faught, E., Leppik, I. E., Shinnar, S., & Zupanc, M. L. (2006). Felbamate: Consensus of current clinical experience. Epilepsy Research, 71(2–3), 89–101.

    Article  PubMed  Google Scholar 

  • Pennell, P. B. (2004). Pregnancy in women who have epilepsy. Neurologic Clinics: Neurology Illnesses and Pregnancy, 22(4), 799–820.

    Google Scholar 

  • Placidi, F., Marciani, M. G., Diomedi, M., Scalise, A., Pauri, F., & Giacomini, P., et al. (2000). Effects of lamotrigine on nocturnal sleep, daytime somnolence and cognitive functions in focal epilepsy. Acta Neurologica Scandinavica, 102(2), 81–86.

    Article  PubMed  CAS  Google Scholar 

  • Pressler, R. M., Binnie, C. D., Coleshill, S. G., Chorley, G. A., & Robinson, R. O. (2006). Effect of lamotrigine on cognition in children with epilepsy. Neurology, 66(10), 1495–1499.

    Article  PubMed  CAS  Google Scholar 

  • Prevey, M. L., Delaney, R. C., Cramer, J. A., Cattanach, L., Collins, J. F., & Mattson, R. H. (1996). Effect of valproate on cognitive functioning. Comparison with carbamazepine. The Department of Veterans Affairs Epilepsy Cooperative Study 264 Group. Archives of Neurology, 53(10), 1008–1016.

    PubMed  CAS  Google Scholar 

  • Pulliainen, V., & Jokelainen, M. (1994). Effects of phenytoin and carbamazepine on cognitive functions in newly diagnosed epileptic patients. Acta Neurologica Scandinavica, 89(2), 81–86.

    Article  PubMed  CAS  Google Scholar 

  • Reinisch, J. M., Sanders, S. A., Mortensen, E. L., & Rubin, D. B. (1995). In utero exposure to phenobarbital and intelligence deficits in adult men. Jama, 274(19), 1518–1525.

    Article  PubMed  CAS  Google Scholar 

  • Rowan, A. J., Ramsay, R. E., Collins, J. F., Pryor, F., Boardman, K. D., & Uthman, B. M., et al. (2005). New onset geriatric epilepsy: A randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology, 64(11), 1868–1873.

    Article  PubMed  CAS  Google Scholar 

  • Saletu, B., Grunberger, J., Linzmayer, L., Schwartz, L. L., Haegele, K. D., & Schechter, P. J. (1986). Psychophysiological and psychometric studies after manipulating the GABA system by vigabatrin, a GABA-transaminase inhibitor. International Journal of Psychophysiology, 4, 63–80.

    Article  PubMed  CAS  Google Scholar 

  • Salinsky, M. C., Binder, L. M., Oken, B. S., Storzbach, D., Aron, C. R., & Dodrill, C. B. (2002). Effects of gabapentin and carbamazepine on the EEG and cognition in healthy volunteers. Epilepsia, 43(5), 482–490.

    Article  PubMed  CAS  Google Scholar 

  • Salinsky, M. C., Spencer, D. C., Oken, B. S., & Storzbach, D. (2004). Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers. Epilepsy & Behavior, 5(6), 894–902.

    Article  CAS  Google Scholar 

  • Salinsky, M. C., Storzbach, D., Spencer, D. S., & Landry, T. (2005a). Topiramate effects on the EEG, alertness, and cognition: A unique profile of AED neurotoxicity. Epilepsia, 46(Suppl. 8), 185.

    Google Scholar 

  • Salinsky, M. C., Storzbach, D., Spencer, D. C., Oken, B. S., Landry, T., & Dodrill, C. B. (2005b). Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers. Neurology, 64(5), 792–798.

    PubMed  CAS  Google Scholar 

  • Schmidt, D., & Elger, C. E. (2004). What is the evidence that oxcarbazepine and carbamazepine are distinctly different antiepileptic drugs? Epilepsy & Behavior, 5(5), 627–635.

    Article  Google Scholar 

  • Smith, D., Baker, G., Davies, G., Dewey, M., & Chadwick, D. W. (1993). Outcomes of add-on treatment with lamotrigine in partial epilepsy. Epilepsia, 34(2), 312–322.

    Article  PubMed  CAS  Google Scholar 

  • Smith Jr., K. R., Goulding, P. M., Wilderman, D., Goldfader, P. R., Holterman-Hommes, P., & Wei, F. (1994). Neurobehavioral effects of phenytoin and carbamazepine in patients recovering from brain trauma: a comparative study. Archives of Neurology, 51(7), 653–660.

    PubMed  Google Scholar 

  • Sulzbacher, S., Farwell, J. R., Temkin, N., Lu, A. S., & Hirtz, D. G. (1999). Late cognitive effects of early treatment with phenobarbital. Clinical Pediatrics, 38(7), 387–394.

    Article  PubMed  CAS  Google Scholar 

  • Sveinbjornsdottir, S., Sander, J. W., Patsalos, P. N., Upton, D., Thompson, P. J., & Duncan, J. S. (1994). Neuropsychological effects of tiagabine, a potential new antiepileptic drug. Seizure, 3(1), 29–35.

    Article  PubMed  CAS  Google Scholar 

  • Thompson, P. J., Baxendale, S. A., Duncan, J. S., & Sander, J. W. (2000). Effects of topiramate on cognitive function. Journal of Neurology, Neurosurgery & Psychiatry, 69, 636–641.

    Article  CAS  Google Scholar 

  • Uvebrant, P., & Bauzienè, R. (1994). Intractable epilepsy in children. The efficacy of lamotrigine treatment, including non-seizure-related benefits. Neuropediatrics, 25(6), 284–289.

    PubMed  CAS  Google Scholar 

  • Vajda, F. J. E., & Eadie, M. J. (2005). Maternal valproate dosage and foetal malformations. Acta Neurologica Scandinavica, 112(3), 137–143.

    Article  PubMed  CAS  Google Scholar 

  • Vermeulen, J., & Aldenkamp, A. P. (1995). Cognitive side-effects of chronic antiepileptic drug treatment: A review of 25 years of research. Epilepsy Research, 22(2), 65–95.

    Article  PubMed  CAS  Google Scholar 

  • Vinten, J., Adab, N., Kini, U., Gorry, J., Gregg, J., & Baker, G. A., et al. (2005). Neuropsychological effects of exposure to anticonvulsant medication in utero. Neurology, 64(6), 949–954.

    PubMed  CAS  Google Scholar 

  • Weintraub, D., Buchsbaum, R., Resor Jr., S. R., & Hirsch, L. J. (2007). Psychiatric and behavioral side effects of the newer antiepileptic drugs in adults with epilepsy. Epilepsy & Behavior, 10(1), 105–110.

    Article  CAS  Google Scholar 

  • Wide, K., Winbladh, B., & Kallen, B. (2004). Major malformations in infants exposed to antiepileptic drugs in utero, with emphasis on carbamazepine and valproic acid: A nation-wide, population-based register study. Acta Paediatrica, 93(2), 174–176.

    Article  PubMed  CAS  Google Scholar 

  • Wolf, S. M., & Forsythe, A. (1978). Behavior disturbance, phenobarbital, and febrile seizures. Pediatrics, 61(5), 728–731.

    PubMed  CAS  Google Scholar 

  • Wolf, S. M., Forsythe, A., Stunden, A. A., Friedman, R., & Diamond, H. (1981). Long-term effect of phenobarbital on cognitive function in children with febrile convulsions. Pediatrics, 68(6), 820–823.

    PubMed  CAS  Google Scholar 

  • Wolf, S. M., Shinnar, S., Kang, H., Gil, K. B., & Moshe, S. L. (1995). Gabapentin toxicity in children manifesting as behavioral changes. Epilepsia, 36(12), 1203–1205.

    Article  PubMed  CAS  Google Scholar 

  • Wong, I. C., Mawer, G. E., & Sander, J. W. (2001). Adverse event monitoring in lamotrigine patients: a pharmacoepidemiologic study in the United Kingdom. Epilepsia, 42(2), 237–244.

    Article  PubMed  CAS  Google Scholar 

  • Wyszynski, D. F., Nambisan, M., Surve, T., Alsdorf, R. M., Smith, C. R., & Holmes, L. B., et al. (2005). Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology, 64(6), 961–965.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, University of Florida, Gainesville, USA

    David W. Loring & Kimford J. Meador

  2. Department of Clinical and Health Psychology, University of Florida, Gainesville, USA

    David W. Loring

  3. Department of Pharmacy Practice, University of Florida, Gainesville, USA

    Susan Marino

  4. McKnight Brain Institute, University of Florida, P.O. Box 100236, Gainesville, FL, 32610-0236, USA

    David W. Loring

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  1. David W. Loring
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  2. Susan Marino
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  3. Kimford J. Meador
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Correspondence to David W. Loring.

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Loring, D.W., Marino, S. & Meador, K.J. Neuropsychological and Behavioral Effects of Antiepilepsy Drugs. Neuropsychol Rev 17, 413–425 (2007). https://doi.org/10.1007/s11065-007-9043-9

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