Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-22T07:54:04.108Z Has data issue: false hasContentIssue false

Lamotrigine in Psychiatry: Pharmacology and Therapeutics

Published online by Cambridge University Press:  07 November 2014

Abstract

Following the introduction of lamotrigine in 1994 as a treatment for epilepsy in the United States, the drug has seen progressively greater application in psychiatry, particularly as a treatment for bipolar disorder. This review critically evaluates the support for lamotrigine use across a broad range of psychiatric disorders as well as discuss its pharmacology, side-effect profile, and interactions with other medications.

Type
Review Articles
Copyright
Copyright © Cambridge University Press 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Leadbetter, R, Messenheimer, J, Bentley, B, Greene, P, Huffman, R, Spaulding, T. Mood-stabilizing properties of lamotrigine: a review of data from controlled clinical trials. Psychiatr Ann. 2002;32:766777.Google Scholar
2. Goldsmith, DR, Wagstaff, AJ, Ibbotson, T, Perry, CM. Lamotrigine: a review of its use in bipolar disorder. Drugs. 2003;63:20292050.Google Scholar
3. Bowden, CL, Karren, NU. Lamotrigine in the treatment of bipolar disorder. Expert Opin Pharmacother. 2002;3:15131519.Google Scholar
4. Lamotrigine. In: Physicians' Desk Reference. 58th ed. Montvale, NJ: Thomson PDR; 2004;15371545.Google Scholar
5. Grunze, H, von Wegerer, J, Greene, RW, Walden, J. Modulation of calcium and potassium currents by lamotrigine. Neuropsychobiology. 1998;38:1313–1138.Google Scholar
6. Ketter, TA, Manji, HK, Post, RM. Potential mechanisms of action of lamotrigine in the treatment of bipolar disorders. J Clin Psychopharmacol. 2003;23:484495.Google Scholar
7. Braga, MFM, Aroniadou-Anderjaska, V, Post, RM, Li, H. Lamotrigine reduces spontaneous and evoked GABAA receptor-mediated synaptic transmission in the basolateral amygdala: implications for its effects in seizure and affective disorders. Neuropharmacology. 2002;42:522529.Google Scholar
8. Shiah, I-S, Yatham, LN, Gau, Y-C, Baker, BG. Effect of lamotrigine on plasma GABA levels in healthy humans. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:419423.Google Scholar
9. Southam, E, Kirby, D, Higgins, GA, Hagan, RM. Lamotrigine inhibits monoamine uptake in vitro and modulates 5-hydrxytryptamine uptake in rats. Eur J Pharmacol. 1998;358:1924.Google Scholar
10. Marcellin, P, de Bony, F, Garret, C, et al. Influence of cirrhosis on lamotrigine pharmacokinetics. Br J Clin Pharmacol. 2001;51:410414.Google Scholar
11. Wootton, R, Soul-Lawton, J, Rolan, PE, et al. Comparison of the pharmacokinetics of lamottigine in patients with chronic renal failure and healthy volunteers. Br J Clin Pharmacol. 1997;43:2327.Google Scholar
12. Chan, V, Morris, RG, Ilett, KF, Tett, SE. Population pharmacokinetics of lamotrigine. Ther Drug Monit. 2001;23:630635.Google Scholar
13. Grasela, TH, Fiedler-Kelly, J, Cox, E, Womble, GP, Risner, ME, Chen, C. Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy. J Clin Pharmacol. 1999;39:373384.Google Scholar
14. Pennell, PB, Newport, DJ, Stowe, ZN, Helmers, SL, Montgomery, JQ, Henry, TR. The impact of pregnancy and childbirth on the metabolism of lamotrigine. Neurology. 2004;62:292295.Google Scholar
15. Tran, TA, Leppik, IE, Blesi, K, Sathanandan, ST, Remmel, R. Lamotrigine clearance during pregnancy. Neurology. 2002;59:251255.Google Scholar
16. Ohman, I, Vitols, S, Tomson, T. Lamotrigine in pregnancy: pharmacokinetics during delivery, in the neonate, and during lactation. Epilepsia. 2000;4:709713.Google Scholar
17. Tomson, T, Öhman, I, Vitols, S. Lamotrigine in pregnancy and lactation: a case report. Epilepsia. 1997;38:10391041.CrossRefGoogle ScholarPubMed
18. Kilpatrick, ES, Forrest, G, Brodie, MJ. Concentration-effect and concentration-toxicity relations with lamotrigine: a prospective study. Epilepsia. 1996;37:534538.Google Scholar
19. Johannessen, SI, Battino, D, Berry, DJ, et al. Therapeutic drug monitoring of the newer antiepileptic drugs. Ther Drug Monit. 2003;25:347363.CrossRefGoogle ScholarPubMed
20. Smith, D, Baker, G, Davies, G, Dewey, M, Chadwick, DW. Outcomes of add-on treatment with lamotrigine in partial epilepsy. Epilepsy. 1993;34:312322.CrossRefGoogle ScholarPubMed
21. Weisleer, RH, Risner, ME, Ascher, JA, Houser, TL. Use of lamotrigine in the treatment of bipolar disorder. In: 1994 Sesquicentennial Annual Meeting New Research Program and Abstracts. Philadelphia, Penn: American Psychiatric Association; 1994;216. NR 611.Google Scholar
22. Ichim, L, Berk, M, Brook, S. Lamotrigine compared with lithium in mania: a double-blind randomized controlled trial. Ann Clin Psychiatry. 2000;12:510.Google Scholar
23. Calabrese, JR, Bowden, CL, Sachs, GS, Ascher, JA, Monaghan, E, Rudd, GD. A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I deptession. J Clin Psychiatry. 1999;60:7988.Google Scholar
24. Bowden, CL, Calabrese, JR, Sachs, G, et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch Gen Psychiatry. 2003;60:392400.Google Scholar
25. Calabrese, JR, Bowden, CL, Sachs, G, et al. A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry. 2003;64:10131024.Google Scholar
26. Goodwin, GM, Bowden, CL, Calabrese, JR, et al. A pooled analysis of 2 placebo-controlled 18-month trials of lamotrigine and lithium maintenance in bipolar I disorder. J Clin Psychiatry. 2004;65:432441.CrossRefGoogle ScholarPubMed
27. Fatemi, SH, Rapport, DJ, Calabrese, JR, Thuras, P. Lamotrigine in rapid-cycling bipolar disorder. J Clin Psychiatry. 1997;58:552–527.Google Scholar
28. Walden, J, Schaerer, L, Schloesser, S, Grunze, H. An open longitudinal study of patients with bipolar rapid cycling treated with lithium or lamotrigine for mood stabilization. Bipolar Disord. 2002;2:336339.Google Scholar
29. Calabrese, JR, Suppes, T, Bowden, CL, et al. A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. J Clin Psychiatry.. 2000;61:840850.Google Scholar
30. Calabrese, JR, Bowden, CL, McElroy, SL, et al. Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder. Am J Psychiatry. 1999;156:10191023.Google Scholar
31. Kusumakar, V, Yatham, LN. An open study of lamotrigine in refractory bipolar depression. Psychiatry Res. 1997;72:145148.Google Scholar
32. Fogelson, DL, Sternbach, H. Lamotrigine treatment of refractory bipolar disorder [letter]. J Clin Psychiatry. 1997;58:271273.Google Scholar
33. Sporn, J, Sachs, G. The anticonvulsant lamotrigine in treatment-resistant manicdepressive illness. J Clin Psychopharmacol. 1997;17:185189.Google Scholar
34. Frye, MA, Ketter, TA, Kimbrell, TA, et al. A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. J Clin Psychopharmacol. 2000;20:607614.Google Scholar
35. Londborg, PD, Cutler, NR, Cunningham, LA, et al. Lamotrigine in the treatment of unipolar depression. In: 1999 Annual Meeting New Research Program and Abstracts. Washington, DC: American Psychiatric Association; 1999;189190. NR 442.Google Scholar
36. Ascher, JA, Batey, SR, Beaman, M, et al. Controlled studies of lamotrigine in unipolar depression. In: 2000 Annwal Meeting New Research Program and Abstracts. Chicago, Ill: American Psychiatric Association; 2000;190191. NR 489.Google Scholar
37. Maltese, TM. Adjunctive lamotrigine treatment for major depression [letter]. Am J Psychiatry. 1999;156:1833.Google Scholar
38. Rocha, FL, Hara, C. Lamotrigine augmentation in unipolar depression. Int Clin Psychopharmacol. 2003;18:9799.Google Scholar
39. Barbee, JG, Jamhour, NJ. Lamotrigine as an augmentation agent in treatment-resistant depression. J Clin Psychiatry. 2002;63:737741.Google Scholar
40. Normann, C, Hummel, B, Lars, MD, et al. Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled, double-blind study. J Clin Psychiatry. 2002;63:337344.Google Scholar
41. Barbosa, L, Berk, M, Vorster, M. A double-blind, randomized, placebo-controlled trial of augmentation with lamotrigine or placebo in patients concomitantly treated with fluoxetine for resistant major depressive episodes. J Clin Psychiatry. 2003;64:403407.Google Scholar
42. Dursun, SM, Deakin, JFW. Augmenting antipsychotic treatment with lamotrigine or topiramate in patients with treatment-resistant schizophrenia: a naturalistic case-series outcome study. J Psychopharmacol. 2001;15:297301.Google Scholar
43. Erfurth, A, Walden, J, Grunze, H. Lamotrigine in the treatment of schizoaffective disorder. Neuropsychobiology. 1998;38:204205.Google Scholar
44. Pinto, OC, Akiskal, HS. Lamotrigine as a promising approach to borderline personality: an open case series without concurrent DSM-IV major mood disorder. J Affect Disord. 1998;51:333343.Google Scholar
45. Brown, ES, Frol, A, Bobadilla, L, Nejtek, VA, Perantie, DC, Dhillon, H. Effect of lamotrigine on mood and cognition in patients receiving chronic exogenous corticosteroids. Psychosomatics. 2003;44:204208.Google Scholar
46. De León, OA, Furmaga, KM. Effect of lamotrigine treatment in epileptic psychosis [letter]. J Clin Psychopharmacol. 1999;19:186.Google Scholar
47. Ramasubbu, R. Lamotrigine treatment for post-stroke pathological laughing and crying. Clin Neuropharmacol. 2003;26:233235.Google Scholar
48. Devarajan, S, Dursun, S. Aggression in dementia with lamotrigine treatment [letter]. Am J Psychiatry. 2000;157:1178.Google Scholar
49. Pachet, A, Friesen, S, Winkelaar, D, Gray, S. Beneficial behavioural effects of lamotrigine in traumatic grain injury. Brain Inj. 2003;17:715722.Google Scholar
50. Davanzo, PA, King, BH. Open trial lamotrigine in the treatment of self-injurious behavior in an adolescent with profound mental retardation. J Child Adolesc Psychopharmacol. 1996;6:273279.CrossRefGoogle Scholar
51. Rosen, MI, Persall, HR, Kosten, TR. The effect of lamotrigine on naloxone-precipitated opiate withdrawal. Drug Alcohol Depend. 1998;52:173176.CrossRefGoogle ScholarPubMed
52. Sierra, M, Phillips, ML, Labert, MV, Senior, C, David, A, Krystal, JH. Lamotrigine in the treatment of depersonalization disorder [lettet]. J Clin Psychiatry. 2001;62:826827.Google Scholar
53. Sierra, M, Phillips, ML, Ivin, G, Krystal, J, David, AS. A placebo-controlled cross-over trial of lamotrigine in depersonalization disorder. J Psychopharmacol 2003;17:103105.Google Scholar
54. McCleane, G. 200 mg daily of lamotrigine has no analgesic effect in neuropathic pain: a randomised, double-blind, placebo controlled trial. Pain. 1999;83:105107.Google Scholar
55. Zakrzewska, J, Chaudhry, Z, Nurmikko, TJ, Patton, DW, Mullens, EL. Lamotrigine (Lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo conttolled crossover trial. Pain. 1997;73:233–230.Google Scholar
56. Eisenberg, E, Lurie, Y, Braker, C, Daoud, D, Ishay, A. Lamotrigine reduces painful diabetic neuropathy: a randomized, controlled study. Neurology. 2001;57:505509.Google Scholar
57. Simpson, DM, McArthur, JC, Olney, R, et al. Lamotrigine for HIV-associated painful sensory neuropathies: a placebo-controlled trial. Neurology. 2003;60:15081514.Google Scholar
58. Bonicalzi, V, Canavero, S, Gerutti, F, Piazza, M, Clemente, M, Chió, . Lamotrigine reduces total postoperative analgesie requirement: a randomized double-hlind, placebo-controlled pilot study. Surgery. 1997;122:567570.Google Scholar
59. Webb, J, Kamali, F. Analgesie effects of lamotrigine and phenytoin on cold-induced pain: a crossover placebo-controlled study in healthy volunteers. Pain. 1998;76:357363.Google Scholar
60. Vestergaard, K, Andersen, G, Gottrup, H, Kristensen, BT, Jensen, TS. Lamotrigine for central poststroke pain: a randomized controlled trial. Neurology. 2001;56:184190.Google Scholar
61. Asnis, G, Bowden, C, Calabrese, J, Sachs, G, Bentley, B, Leadbetter, R. Safety and tolerability of lamotrigine in bipolar I disorder. Poster presented at: Annual Meeting of the New Clinical Dtug Evaluation Unit; May 27-30, 2003. Boca Raton, FL.Google Scholar
62. Ettinger, AB, Weisbrot, DM, Saracco, J, Dhoon, A, Kanner, A, Devinsky, O. Positive and negative psychotropic effects of lamotrigine in patients with epilepsy and mental retardation. Epilepsia. 1998;39:874877.Google Scholar
63. Beran, RG, Gibson, RJ. Aggtessive behaviour in intellectually challenged patients with epilepsy treated with lamotrigine. Epilepsia. 1998;39:280282.Google Scholar
64. Sotero de Menezes, MA, Rho, JM, Murphy, P, Cheyette, S. Lamotrigine-induced tic disorder: report of five pediatric cases. Epilepsia. 2000;41:862867.Google Scholar
65. Lombroso, CT. Lamotrigine-induced tourettism. Neurology. 1999;52:11911194.Google Scholar
66. Margolese, HC, Beauclair, L, Szkrumelak, N, Chouinard, G. Hypomania induced by adjunctive lamotrigine. Am J Psychiatry. 2003;160:183184.Google Scholar
67. Meador, KJ, Loring, DW, Ray, PG, et al. Diffetential cognitive and behavioral effects of carbamazepine and lamotrigine. Neurology. 2001;56:11771182.Google Scholar
68. Overstreet, K, Costanza, C, Behling, C, Hassanin, T, Masliah, E. Fatal progressive hepatic necrosis associated with lamotrigine treatment: a case report and literature review. Dig Dis Sci. 2002;47:19211925.Google Scholar
69. Sauvé, G, Bresson-Hadni, S, Prost, P, et al. Acute hepatitis after lamotrigine administration. Dig Dis Sci. 2000;45:18741877.Google Scholar
70. Esfahani, FE, Dasheiff, RM. Anemia associated with lamotrigine. Neurology. 1997;49:306307.Google Scholar
71. Solvason, HB. Agranulocytosis associated with lamotrigine [letter]. Am J Psychiatry. 2000;157:1704.Google Scholar
72. Fadul, CE, Meyer, LP, Jobst, BC, Cornell, CJ, Lewis, LD. Agranulocytosis associated with lamotrigine in a patient with low-grade glioma. Epilepsia. 2002;43:199200.Google Scholar
73. Isojärvi, JIT, Rättyä, J, Myllylä, VV, et al. Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy. Ann Neurol. 1998;43:446451.Google Scholar
74. Stephen, LJ, Kwan, P, Shapiro, D, Dominiczak, M, Brodie, MJ. Hormone profiles in young adults with epilepsy treated with sodium valproate or lamotrigine monotherapy. Epilepsia. 2001;42:10021006.Google Scholar
75. Morrell, MJ, Isojärvi, J, Taylor, AE, et al. Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy. Epilepsy Res. 2003;54:189199.Google Scholar
76. Røste, LS, Taubøll, E, Berner, A, Isojärvi, JIT, Gjerstad, L. Valproate, but not lamotrigine, induces ovarian morphological changes in Wistar rats. Exp Toxic Pathol. 2001;52:545552.Google Scholar
77. Biton, V. Effect of antiepileptic dtugs on bodyweight: overview and clinical implications for the treatment of epilepsy. CNS Drugs. 2003;17:781791.Google Scholar
78. Devinsky, O, Vuong, A, Hammer, A, Barrett, PS. Stable weight during lamotrigine therapy: a review of 32 studies. Neurology. 2000;54:973975.Google Scholar
79. Biton, V, Mirza, W, Montouris, G, Vuong, A, Hammer, AE, Barrett, PS. Weight change associated with valproate and lamotrigine monotherapy in patients with epilepsy. Neurology. 2001;56:172177.Google Scholar
80. Ginsberg, LD, Bowden, CL, Calabrese, JR, Sachs, GS, Ketter, TA. Effects of mood stabilizerson body weight in bipolar I disorder. In: 156th Annual Meeting New Research Abstracts. San Francisco, Calif: American Psychiatric Association; 2003;173174. NR463.Google Scholar
81. Avoni, P, Contin, M, Riva, R, Albani, F, Liguori, R, Baruzzi, A. Dysgeusia in epileptic patients treated with lamotrigine: report of three cases. Neurology. 2001;57:1521.Google Scholar
82. O'Donnell, J, Bateman, DN. Lamotrigine overdoes in an adult. Clin Toxicol. 2000;38:659660.Google Scholar
83. Gelisse, Ph, Kissani, N, Crespel, A, Jafari, H, Baldy-Moulinier, M. Is there a lamotrigine withdrawal syndrome? Acta Neurol Scand. 2002;105:232234.Google Scholar
84. Tennis, P, Eldridge, RR. Preliminary results on pregnancy outeomes in women using lamotrigine. Epilepsia. 2002;43:11611167.Google Scholar
85. Chaudron, LH, Jefferson, JW. Mood stabilizers during breastfeeding: a review. J Clin Psychiatry. 2000;61:7990.Google Scholar
86. Labiner, DM. Lamotrigine and rash: scratching beneath the sutface. J Clin Psychiatry. 2002;63:10101011.Google Scholar
87. Roujeau, JC, Stern, RS. Severe adverse cutaneous reactions to drugs. N Engl J Med. 1994;331:12721285.Google Scholar
88. Besag, FMC. Approaches to reducing the incidence of lamotrigine-induced rash. CNS Drugs. 2000;13:2133.Google Scholar
89. Messenheimer, J, Mullens, EL, Giorgi, L, Young, F. Safety review of adult clinical trial experience with lamotrigine. Drug Saf. 1998;18:281296.Google Scholar
90. Wong, ICK, Mawer, GE, Sander, JW. Factors influencing the incidence of lamotrigine-related skin rash. Ann Pharmacother. 1999;33:10371042.Google Scholar
91. Schlienger, RG, Shapiro, LE, Shear, NH. Lamotrigine-induced severe cutaneous adverse reactions. Epilepsia. 1998;39:522526.Google Scholar
92. Shepherd, GM. Hypersensitivity reactions to drugs: evaluation and management. Mt Sinai J Med. 2003;70:113125.Google ScholarPubMed
93. Calabrese, JR, Sullivan, JR, Bowden, CL, et al. Rash in multicenter trials of lamotrigine in mood disorders: clinical relevance and management. J Clin Psychiatry. 2002;63:10121019.Google Scholar
94. Lardizabal, DV, Morris, HH, Hovinga, CA, Del Mar Carreña, M. Tolerability and pharmacokinetics of oral loading with lamotrigine in epilepsy monitoring units. Epilepsia. 2003;44:536539.Google Scholar
95. Roujeau, J-C, Kelley, JP, Naldi, L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333:1601607.Google Scholar
96. Ruble, J, Matsuo, F. Anticonvutsant-induced cutaneous reactions: incidence, mechanisms and management. CNS Drugs. 1999;12:215236.Google Scholar
97. Liston, HL, Markowitz, JS, DeVane, CL. Drug glucuronidation in clinical psychopharmacology. J Clin Psychopharmacol. 2001;21:500515.Google Scholar
98. de Leon, J. Glucuronidation enzymes, genes and psychiatry. Int J Neuropsychopharmacol. 2003;6:5772.Google Scholar
99. Kanner, AM, Frey, M. Adding valproate to lamotrigine: a study of their pharmacokinetic interaction. Neurology. 2000;55:588591.Google Scholar
100. Anderson, GD, Yau, MK, Gidal, BE, et al. Bidirectional interaction of valproate and lamotrigine in healthy subjects. Clin Pharmacol Ther. 1996;60:145156.Google Scholar
101. Hennessy, MJ, Wiles, CM. Lamotrigine encephalopathy [letter]. Lancet. 1996;347:347348.Google Scholar
102. Kaufman, KR, Gerner, R. Lamotrigine toxicity secondary to sertraline. Seizure. 1998;7:163165.Google Scholar
103. Besag, FMC, Berry, DJ, Pool, F. Methsuximide lowers lamotrigine blood levels: a pharmacokinetic antiepileptic drug interaction. Epilepsia. 2000;41:624627.Google Scholar
104. Ebert, U, Thong, NQ, Oertel, R, Kirch, W. Effects of rifampicin and cimetidine on pharmacokinetics and pharmacodynamics of lamotrigine in healthy subjects. Eur J Clin Pharmacol. 2000;56:299304.Google Scholar
105. May, TW, Rambeck, B, Jurgens, U. Influence of oxcarbazepine and methsuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication: results of a retrospective study. Ther Drug Monit. 1999;21:175181.Google Scholar
106. Sabeers, A, Öhman, I, Christensen, J, Tomson, T. Oral contraceptives reduce lamotrigine plasma levels. Neurology. 2003;61:570571.Google Scholar
107. Anderson, GD, Gidal, BE, Messenheimer, JA, Gilliam, FG. Time course of lamotrigine de-induction: impact of step-wise withdrawal of carbamazepine or phenytoin. Epilepsy Res. 2002;49:211217.Google Scholar
108. Doose, DR, Brodie, MJ, Wilson, EA, et al. Topiramate and lamotrigine pharmacokinetics during repetitive monotherapy and combination therapy in epilepsy patients. Epilepsia. 2003;44:917922.Google Scholar
109. May, TW, Rambeck, B, Jurgens, U. Serum concentrations of levetiracetam in epileptic patients: the influence of dose and co-medication. Ther Drug Monit. 2003;25:690699.Google Scholar
110. Mataringa, M-I, May, TW, Rambeck, B. Does lamotrigine influence valproate concentrations? Ther Drug Monit. 2002;24:631636.Google Scholar
111. Gidal, BE, Rutecki, P, Shaw, R, Maly, MM, Collins, DM, Pitterle, ME. Effect of lamotrigine on carbamazepine expoxide/carbamazepine serum concentration ratios in adult patients with epilepsy. Epilepsy Res. 1997;28:207211.Google Scholar
112. Chen, C, Veronese, L, Yin, Y. The effects of lamotrigine on the pharmacokinetics of lithium. Br J Clin Pharmacol. 2000;50:193195.Google Scholar
113. Kossen, M, Selten, JP, Kahn, RS. Elevated clozapine plasma level with lamotrigine [letter]. Am J Psychiatry. 2001;158:1930.Google Scholar
114. Besag, FMC, Berry, DJ, Pool, F, Newbery, JE, Subel, B. Carbamazepine toxicity with lamotrigine: pharmacokinetic or pharmacodynamic interaction? Epilepsia. 1998;39:183187.Google Scholar