0
0

Chapter 39. Lamotrigine

David E. Kemp, M.D.; David J. Muzina, M.D.; Keming Gao, M.D., Ph.D.; Joseph R. Calabrese, M.D.
DOI: 10.1176/appi.books.9781585623860.432143

Sections

Excerpt

The initial premise in evaluating lamotrigine as an anticonvulsant was that it might possess sufficient dihydrofolate reductase inhibition to decrease folate activity, a mechanism known to reduce epileptic effects. Although its antifolate properties were only modest, anticonvulsant effects were significant. During the clinical development of lamotrigine as a treatment for intractable seizures, improved mood in lamotrigine-treated patients was anecdotally reported (Jawad et al. 1989; Smith et al. 1993). Indeed, antiepileptic drugs (AEDs) have been described as a heterogeneous class of medications with a diverse range of utility in psychiatry with variable effects on mood (Muzina et al. 2005).

Your session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
 
Username
Password
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

FIGURE 39–1. Chemical structure of lamotrigine, with chemical structures of valproic acid and carbamazepine for comparison.

FIGURE 39–2. Clinical management of rash related to lamotrigine treatment.CBC = complete blood count; LFT = liver function test.Source. Reprinted from Calabrese JR, Sullivan JR, Bowden CL, et al: "Rash in Multicenter Trials of Lamotrigine in Mood Disorders: Clinical Relevance and Management." Journal of Clinical Psychiatry 63:1012–1019, 2002. Copyright 2000, Physicians Postgraduate Press. Used with permission.
Table Reference Number
TABLE 39–1. Summary of multicenter randomized, controlled trials of lamotrigine in mood disorders
Table Reference Number
TABLE 39–2. Recommended titration schedule for lamotrigine for patients with bipolar disorder taking valproate
Table Reference Number
TABLE 39–3. Recommended titration schedule for lamotrigine when used as monotherapy and when added to an enzyme-inducing antiepileptic drug regimen* (without valproate)

References

Anand A, Charney DS, Oren DA, et al: Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: support for hyperglutamatergic effects of N-methyl-D-aspartate receptor antagonists. Arch Gen Psychiatry 57:270–276, 2000
[PubMed]
 
Ayala G, Matsumoto H, Gumnit R: Excitability changes and inhibitory mechanisms in neurocortical neurons during seizures. J Neurophysiol 33:73–85, 1970
[PubMed]
 
Besag F, Ng G, Pool F: Successful re-introduction of lamotrigine after initial rash. Seizure 9:282–286, 2000
[PubMed]
 
Bourin M, Masse F, Hascoet M: Evidence for the activity of lamotrigine at 5-HT(1A) receptors in the mouse forced swimming test. J Psychiatry Neurosci 30:275–282, 2005
[PubMed]
 
Bowden CL, Calabrese JR, Ascher J, et al: Spectrum of efficacy of lamotrigine in bipolar disorder: overview of double-blind, placebo-controlled studies. Presented at the American College of Neuropsychopharmacology (ACNP) Annual Meeting, San Juan, PR, December 2000
 
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 60:392–400, 2003
[PubMed]
 
Bowden CL, Asnis GM, Ginsberg LD, et al: Safety and tolerability of lamotrigine for bipolar disorder. Drug Saf 27:173–184, 2004
[PubMed]
 
Bowden CL, Calabrese JR, Ketter TA, et al: Impact of lamotrigine and lithium on weight in obese and nonobese patients with bipolar I disorder. Am J Psychiatry 163:1199–1201, 2006
[PubMed]
 
Bradburn NM: The Structure of Psychological Well-Being. Chicago, IL, Alpine, 1969
 
Brown EB, McElroy SL, Keck PE Jr, et al: A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression. J Clin Psychiatry 67:1025–1033, 2006
[PubMed]
 
Brown ES, Perantie DC, Dhanani N, et al: Lamotrigine for bipolar disorder and comorbid cocaine dependence: a replication and extension study. J Affect Disord 93:219–222, 2006
[PubMed]
 
Calabrese JR, Bowden CL, McElroy SL, et al: Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder. Am J Psychiatry 156:1019–1023, 1999a
 
Calabrese JR, Bowden CL, Sachs GS, et al: A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. J Clin Psychiatry 60:79–88, 1999b
 
Calabrese JR, Suppes T, Bowden C, et al: A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. J Clin Psychiatry 61:841–850, 2000
[PubMed]
 
Calabrese JR, Sullivan JR, Bowden CL, et al: Rash in multicenter trials of lamotrigine in mood disorders: clinical relevance and management. J Clin Psychiatry 63:1012–1019, 2002
[PubMed]
 
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 64:1013–1024, 2003
[PubMed]
 
Calabrese JR, Goldberg JF, Ketter TA, et al: Recurrence in bipolar I disorder: a post hoc analysis excluding relapses in two double-blind maintenance studies. Biol Psychiatry 59:1061–1064, 2006
[PubMed]
 
Calabrese JR, Huffman RF, White RL, et al: Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials. Bipolar Disord 10:323–333, 2008
[PubMed]
 
Cheung H, Kamp D, Harris E: An in vitro investigation of the action of lamotrigine on neuronal voltage-activated sodium channels. Epilepsy Res 13:107–112, 1992
[PubMed]
 
Crumrine RC, Bergstrand K, Cooper AT, et al: Lamotrigine protects hippocampal CA1 neurons from ischemic damage after cardiac arrest. Stroke 28:2230–2236, 1997
[PubMed]
 
Cunnington M, Tennis P: International Lamotrigine Pregnancy Registry Scientific Advisory Committee: Lamotrigine and the risk of malformations in pregnancy. Neurology 64:955–960, 2004
 
Daly K, Fatemi S: Lamotrigine and impulse behavior. Can J Psychiatry 44:395–396, 1999
[PubMed]
 
Davanzo P, King B: Open trial of lamotrigine in the treatment of self-injurious behavior in an adolescent with profound mental retardation. J Child Adolesc Psychopharmacol 6:273–279, 1996
[PubMed]
 
Devarajan S, Dursun S: Aggression in dementia with lamotrigine treatment. Am J Psychiatry 157:1178, 2000
[PubMed]
 
DeVeaugh-Geiss J, Ascher J, Brook S, et al: Safety and tolerability of lamotrigine in controlled monotherapy trials in mood disorders. Presented at the American College of Neuropsychopharmacology (ACNP) Annual Meeting, San Juan, PR, December 2000
 
Dolk H, Jentink J, Loane M, et al: Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations? Neurology 71:714–722, 2008
[PubMed]
 
Dubovsky SL: Calcium antagonists in manic-depressive illness. Neuropsychobiology 27:184–192, 1993
[PubMed]
 
Erfurth A, Amann BA, Grunze H: Female genital disorder as adverse symptom of lamotrigine treatment: a serotonergic effect? Neuropsychobiology 38:200–201, 1998a
 
Erfurth A, Walden J, Grunze H: Lamotrigine in the treatment of schizoaffective disorder. Neuropsychobiology 38:204–205, 1998b
 
Fervenza FC, Kanakiriya S, Kunau RT, et al: Acute granulomatous interstitial nephritis and colitis in anticonvulsant hypersensitivity syndrome associated with lamotrigine treatment. Am J Kidney Dis 36:1034–1040, 2000
[PubMed]
 
Fix OK, Peters MG, Davern TJ: Eosinophilic hepatitis caused by lamotrigine. Clin Gastroenterol Hepatol 4:xxvi, 2006
 
Gabriel A: Lamotrigine adjunctive treatment in resistant unipolar depression: an open, descriptive study. Depress Anxiety 23:485–488, 2006
[PubMed]
 
Geddes JR, Calabrese JR, Goodwin GM: Lamotrigine for treatment of bipolar depression: an independent meta-analysis and meta-regression of individual patient data from 5 randomized trials. Br J Psychiatry Br J Psychiatry 194:4–9, 2009
[PubMed]
 
Ghaemi SN, Pardo RB, Hsu DJ: Strategies for preventing the recurrence of bipolar disorder. J Clin Psychiatry 65 (suppl):16–23, 2004
 
GlaxoSmithKline: Lamictal (lamotrigine) prescribing information. Research Triangle Park, NC, GlaxoSmithKline, May 2007. Available at: http://us.gsk.com/products/assets/us_lamictal.pdf
 
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 65:432–441, 2004
[PubMed]
 
Grunze H, von Wegerer J, Greene RW, et al: Modulation of calcium and potassium currents by lamotrigine. Neuropsychobiology 38:131–138, 1998
[PubMed]
 
Guberman A, Besag F, Brodie M, et al: Lamotrigine-associated rash: risk/benefit considerations in adults and children. Epilepsia 40:985–991, 1999
[PubMed]
 
Hahn CG, Gyulai L, Baldassano CF, et al: The current understanding of lamotrigine as a mood stabilizer. J Clin Psychiatry 65:791–804, 2004
[PubMed]
 
Harrison N, Simmonds M: Quantitative studies on some antagonists of N-methyl-D-aspartate in slices of rat cerebral cortex. Br J Pharmacol 84:381–391, 1985
[PubMed]
 
Hertzberg M, Butterfield M, Feldman M, et al: A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder. Biol Psychiatry 45:1226–1229, 1999
[PubMed]
 
Holmes LB, Wyszynski DF, Baldwin EJ, et al: Increased risk for nonsyndromic cleft palate among infants exposed to lamotrigine during pregnancy. Birth Defects Res A Clin Mol Teratol 76:318, 2006
 
Jawad S, Richens A, Goodwin G, et al: Controlled trial of lamotrigine (Lamictal) for refractory partial seizures. Epilepsia 30:656–663, 1989
 
Kemp DE, Gilmer WS, Fleck J, et al: An association of intrusive, repetitive phrases with lamotrigine treatment in bipolar II disorder. CNS Spectr 12:106–111, 2007
[PubMed]
 
Ketter TA, Greist JH, Graham JA, et al: The effect of dermatologic precautions on the incidence of rash with addition of lamotrigine in the treatment of bipolar I disorder: a randomized trial. J Clin Psychiatry 67:400–406, 2006
[PubMed]
 
Lang D, Wang C: Lamotrigine and phenytoin interactions on ionic channels present in N4TG1 and GH3 clonal cells. Soc Neurosci Abs 17:1256, 1991
 
Lang D, Wang C, Cooper B: Lamotrigine, phenytoin, and carbamazepine interactions on the sodium current present in N4TG1 mouse neuroblastoma cells. J Pharmacol Exp Ther 266:829–835, 1993
[PubMed]
 
Laurenza A, Asnis G, Beaman M, et al: A double-blind, placebo-controlled study supporting the efficacy of lamotrigine in unipolar depression. Bipolar Disord 1 (suppl):39–40, 1999
 
Leach MJ, Marden CM, Miller AA: Pharmacological studies on lamotrigine, a novel potential antiepileptic drug, II: neurochemical studies on the mechanism of action. Epilepsia 27:490–497, 1986
[PubMed]
 
Leach MJ, Lees G, Riddall DR: Lamotrigine: mechanisms of action, in Antiepileptic Drugs, 4th Edition. Edited by Levy RH, Mattson RH, Meldrum BS. New York, Raven, 1995, pp 861–869
 
Lofton AL, Klein-Schwartz W: Evaluation of lamotrigine toxicity reported to poison control centers. Ann Pharmacother 38:1811–1815, 2004
[PubMed]
 
Lombroso C: Lamotrigine-induced tourettism. Neurology 52:1191–1194, 1999
[PubMed]
 
Maj R, Fariello RG, Ukmar G, et al: PNU-151774E protects against kainate-induced status epilepticus and hippocampal lesions in the rat. Eur J Pharmacol 359:27–32, 1998
[PubMed]
 
May TW, Rambeck B, Jurgens U: Serum concentrations of lamotrigine in epileptic patients: the influence of dose and comedication. Ther Drug Monit 18:523–531, 1996
[PubMed]
 
McDonald MA, Favilla I: Visual loss in a patient with lamotrigine-induced cicatrizing conjunctivitis. Clin Exp Ophthalmol 31:541–543, 2003
[PubMed]
 
Messenheimer JA, Mullens EL, Giorgi L, et al: Safety review of adult clinical trial experience with lamotrigine. Drug Saf 18:281–296, 1998
[PubMed]
 
Mewasingh L, Aylett S, Kirkham F, et al: Hyponatraemia associated with lamotrigine in cranial diabetes insipidus. Lancet 356:656, 2000
[PubMed]
 
Miller AA, Wheatley P, Sawyer DA, et al: Pharmacological studies on lamotrigine, a novel antiepileptic drug: anticonvulsant profile in mice and rats. Epilepsia 27:483–489, 1986
[PubMed]
 
Muzina DJ, Elhaj O, Gajwani P, et al: Lamotrigine and antiepileptic drugs as mood stabilizers in bipolar disorder. Acta Psychiatr Scand 111 (suppl):21–28, 2005
 
Newport DJ, Stowe ZN, Viguera AC, et al: Lamotrigine in bipolar disorder: efficacy during pregnancy. Bipolar Disord 10:432–436, 2008
[PubMed]
 
Ohman I, Vitols S, Tomson T: Lamotrigine in pregnancy: pharmacokinetics during delivery, in the neonate, and during lactation. Epilepsia 41:709–713, 2000
[PubMed]
 
Pearlin L, Schooler C: The structure of coping. J Health Soc Behav 19:2–21, 1978
[PubMed]
 
Pennell PB: Antiepileptic drug pharmacokinetics during pregnancy and lactation. Neurology 61:S35–S42, 2003
 
Pennell PB, Newport DJ, Stowe ZN, et al: The impact of pregnancy and childbirth on the metabolism of lamotrigine. Neurology 62:292–295, 2004
[PubMed]
 
Pinto O, Akiskal H: Lamotrigine as a promising approach to borderline personality: an open case series without DSM-IV major mood disorder. J Affect Disord 51:333–343, 1998
[PubMed]
 
Post R, Weiss S, Pert A: Differential effects of carbamazepine and lithium on sensitization and kindling. Prog Neuropsychopharmacol Biol Psychiatry 8:425–434, 1984
[PubMed]
 
Post R, Nolen WA, Kupka RW, et al: The Stanley Foundation Bipolar Network, I: rationale and methods. Br J Psychiatry Suppl 41:S169–S176, 2001
 
Reimers A, Helde G, Brodtkorb E: Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations. Epilepsia 46:1414–1417, 2005
[PubMed]
 
Rubio G, Lopez-Munoz F, Alamo C: Effects of lamotrigine in patients with bipolar disorder and alcohol dependence. Bipolar Disord 8:289–293, 2006
[PubMed]
 
Saba G, Dumortier G, Kalalou K, et al: Lamotrigine-clozapine combination in refractory schizophrenia: three cases. J Neuropsychiatry Clin Neurosci 14:1, 2002
 
Sabers A, Buchholt J, Uldall P, et al: Lamotrigine plasma levels reduced by oral contraceptives. Epilepsy Res 47:151–154, 2001
[PubMed]
 
Sabers A, Ohman I, Christensen J, et al: Oral contraceptives reduce lamotrigine plasma levels. Neurology 26:570–571, 2003
 
Sachs G, Bowden CL, Calabrese JR, et al: Effects of lamotrigine and lithium on body weight during maintenance treatment of bipolar I disorder. Bipolar Disord 8:175–181, 2006
[PubMed]
 
Sarzi-Puttini P, Panni B, Cazzola M, et al: Lamotrigine-induced lupus. Lupus 9:555–557, 2000
[PubMed]
 
Sbei M, Campellone J: Stupor from lamotrigine toxicity. Epilepsia 42:1082–1083, 2001
[PubMed]
 
Schaffer A, Zucker P, Levitt A: Randomized, double-blind pilot trial comparing lamotrigine versus citalopram for the treatment of bipolar depression. J Affect Disord 96:95–99, 2006
[PubMed]
 
Shiah IS, Yatham LN, Lam RW, et al: Effects of lamotrigine on the 5-HT1A receptor function in healthy human males. J Affect Disord 49:157–162, 1998
[PubMed]
 
Showalter P, Kimmel D: Stimulation of consciousness and cognition after severe brain injury. Brain Inj 14:997–1001, 2000
[PubMed]
 
Sierra M, Baker D, Medford N, et al: Lamotrigine as an add-on treatment for depersonalization disorder: a retrospective study of 32 cases. Clin Neuropharmacol 29:253–258, 2006
[PubMed]
 
Smith D, Chadwick D, Baker G, et al: Seizure severity and the quality of life. Epilepsia 34 (suppl):S31–S35, 1993
 
Southam E, Pereira R, Stratton SC, et al: Effect of lamotrigine on the activities of monoamine oxidases A and B in vitro and on monoamine disposition in vivo. Eur J Pharmacol 519:237–245, 2005
[PubMed]
 
Spearing MK, Post RM, Leverich GS, et al: Modification of the Clinical Global Impressions (CGI) scale for use in bipolar illness (BP): the CGI-BP. Psychiatry Res 73:159–171, 1997
[PubMed]
 
Stefani A, Spadoni F, Sinischali A, et al: Lamotrigine inhibits Ca2+ currents in cortical neurons: functional implications. Eur J Pharmacol 307:113–116, 1996
[PubMed]
 
Stenbom Y, Tonnby B, Hagberg B: Lamotrigine in Rett syndrome: treatment experience from a pilot study. Eur Child Adolesc Psychiatry 7:49–52, 1998
[PubMed]
 
Tavernor S, Wong I, Newton R, et al: Rechallenge with lamotrigine after initial rash. Seizure 4:67–71, 1995
[PubMed]
 
Tekin S, Aykut-Bingol C, Tanridag T, et al: Antiglutamatergic therapy in Alzheimer's disease: effects of lamotrigine. J Neural Transm 105:295–303, 1998
[PubMed]
 
van der Loos M, Nolen WA, Vieta E, et al: Lamotrigine as add-on to lithium in bipolar depression. Presented at the fifth European Stanley Conference on Bipolar Disorder, Barcelona, Spain, October 2006
 
von Wegerer J, Hesslinger B, Berger M, et al: A calcium antagonistic effect of the new antiepileptic drug lamotrigine. Eur Neuropsychopharmacol 7:77–78, 1997
 
Weintraub D, Buchsbaum R, Resor SR Jr, et al: Effect of antiepileptic drug comedication on lamotrigine clearance. Arch Neurol 62:1432–1436, 2005
[PubMed]
 
Xie X, Hagan RM: Cellular and molecular actions of lamotrigine: possible mechanisms of efficacy in bipolar disorder. Neuropsychobiology 38:119–130, 1998
[PubMed]
 
Yau M, Wargin W, Wolf K, et al: Effect of valproate on the pharmacokinetics of lamotrigine at steady state. Epilepsia 33 (suppl):82, 1992
 
+

CME Activity

Add a subscription to complete this activity and earn CME credit.
Sample questions:
1.
Lamotrigine has been shown to
2.
Oral lamotrigine
3.
Oral lamotrigine is approved by the U.S. Food and Drug Administration (FDA) for which of the following indications?
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Related Content
Articles
Books
Helping Parents, Youth, and Teachers Understand Medications for Behavioral and Emotional Problems: A Resource Book of Medication Information Handouts, 3rd Edition > Chapter 34.  >
What Your Patients Need to Know About Psychiatric Medications, 2nd Edition > Chapter 41.  >
APA Practice Guidelines > Chapter 6.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 26.  >
Topic Collections
Psychiatric News
Read more at Psychiatric News >>
PubMed Articles
 
  • Print
  • PDF
  • E-mail
  • Chapter Alerts
  • Get Citation