Abstract
We developed this lamotrigine guideline using drug prescribing information and reviewing the available literature on relevant neuropsychiatric disorders in populations without intellectual disabilities because of the dearth of available literature on the population with intellectual disabilities. This guideline includes indications; contraindications; assessments prior to and during treatment; dosing with particular focus on dosing modifications required by drug–drug interactions, or personal characteristics; and adverse drug reactions. The procedures contained in this guideline may not fully account for all of the possible risks of treatment in this population because of the limited studies available; thus, there will be a need to periodically update this guideline as new information becomes available. Nevertheless, we believe that this guideline provides a useful resource for clinicians who treat epilepsy or mood disorders in adult individuals with intellectual disabilities. A lamotrigine drug utilization review that summarizes this guideline is described.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Aiken, C. B., & Orr, C. (2010). Rechallenge with lamotrigine after a rash: a prospective case series and review of the literature. Psychiatry (Edgmont), 7, 27–32.
American Psychiatric Association. (2002). Practice guideline for the treatment of patients with bipolar disorder (revision). The American Journal of Psychiatry, 159(4 Suppl), 1–50.
Anderson, G. D., Gidal, B. E., Messenheimer, J. A., & Gilliam, F. G. (2002). Time course of lamotrigine de-induction: impact of step-wise withdrawal of carbamazepine or phenytoin. Epilepsy Research, 49, 211–217.
Arana, A., Wentworth, C. E., Ayuso-Mateos, J. L., & Arellano, F. M. (2010). Suicide-related events in patients treated with antiepileptic drugs. The New England Journal of Medicine, 363, 542–551.
Argikar, U. A., & Remmel, R. P. (2009). Variation in glucuronidation of lamotrigine in human liver microsomes. Xenobiotica, 39, 355–363.
Arif, H., Buchsbaum, R., Pierro, J., Whalen, M., Sims, J., Resor, S. R., Jr., et al. (2010). Comparative effectiveness of 10 antiepileptic drugs in older adults with epilepsy. Archives of Neurology, 67, 408–415.
Arif, H., Buchsbaum, R., Weintraub, D., Koyfman, S., Salas-Humara, C., Bazil, C. W., Resor, S. R., Jr., & Hirsch, L. J. (2007). Comparison and predictors of rash associated with 15 antiepileptic drugs. Neurology, 68, 1701–1709.
Arif, H., Buchsbaum, R., Weintraub, D., Pierro, J., Resor, S. R., Jr., & Hirsch, L. J. (2009). Patient-reported cognitive side effects of antiepileptic drugs: predictors and comparison of all commonly used antiepileptic drugs. Epilepsy & Behavior, 14, 202–209.
Bastuji-Garin, S., Rzany, B., & Stern, R. S. (1993). Clinical classification of cases of toxic epidermal necrolysis: Stevens-Johnson syndrome and erythema multiforme. The Archives of Dermatology, 129, 92–96.
Bell, G. S., Mula, M., & Sander, J. W. (2009). Suicidality in people taking antiepileptic drugs: what is the evidence? CNS Drugs, 23, 281–292.
Ben-Menachem, E. (2007). Weight issues for people with epilepsy—a review. Epilepsia, 48(Suppl 9), 42–45.
Beran, R. G., & Gibson, R. J. (1998). Aggressive behaviour in intellectually challenged patients with epilepsy treated with lamotrigine. Epilepsia, 39, 280–282.
Besag, F. M., Berry, D. J., Pool, F., Newbery, J. E., & Subel, B. (1998). Carbamazepine toxicity with lamotrigine: pharmacokinetic or pharmacodynamic interaction? Epilepsia, 39, 183–187.
Bhaumik, S., Branford, D., Duggirala, C., & Ismail, I. A. (1997). A naturalistic study of the use of vigabatrin, lamotrigine and gabapentin in adults with learning disabilities. Seizure, 6, 127–133.
Biton, V. (2006). Pharmacokinetics, toxicology and safety of lamotrigine in epilepsy. Expert Opinion on Drug Metabolism & Toxicology, 2, 1009–1018.
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, 400–406.
Botts, S., Diaz, F. J., Santoro, V., Spina, E., Muscatello, M. R., Cogollo, M., et al. (2008). Estimating the effects of co-medications on plasma olanzapine concentrations by using a mixed model. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 32, 1453–1458.
Bowden, C. L., Asnis, G. M., Ginsberg, L. D., Bentley, B., Leadbetter, R., & White, R. (2004). Safety and tolerability of lamotrigine for bipolar disorder. Drug Safety, 27, 173–184.
Bowden, C. L., Calabrese, J. R., Ketter, T. A., Sachs, G. S., White, R. L., & Thompson, T. R. (2006). Impact of lamotrigine and lithium on weight in obese and nonobese patients with bipolar I disorder. The American Journal of Psychiatry, 163, 1199–1201.
Brandt, C., Fueratsch, N., Boehme, V., Kramme, C., Pieridou, M., Villagran, A., et al. (2007). Development of psychosis in patients with epilepsy treated with lamotrigine: report of six cases and review of the literature. Epilepsy & Behavior, 11, 133–139.
Brodie, M. J. (2010). Antiepileptic drug therapy the story so far. Seizure, 19, 650–655.
Brodie, M. J., Wilson, E. A., Wesche, D. L., Alvey, C. W., Randinitis, E. J., Posvar, E. L., et al. (2005). Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy. Epilepsia, 46, 1407–1413.
Buchanan, N. (1995). The efficacy of lamotrigine on seizure control in 34 children, adolescents and young adults with intellectual and physical disability. Seizure, 4, 233–236.
Burchell, B., Soars, M., Monaghan, G., Cassidy, A., Smith, D., & Ethell, B. (2000). Drug-mediated toxicity caused by genetic deficiency of UDP-glucuronosyltransferases. Toxicology Letters, 112–113, 333–340.
Calabrese, J. R., Sullivan, J. R., Bowden, C. L., Suppes, T., Goldberg, J. F., Sachs, G. S., et al. (2002). Rash in multicenter trials of lamotrigine in mood disorders: clinical relevance and management. The Journal of Clinical Psychiatry, 63, 1012–1019.
Carpay, J. A., Aalbers, K., Graveland, G. A., & Engelsman, M. (2009). Retention of new AEDs in institutionalized intellectually disabled patients with epilepsy. Seizure, 18, 119–123.
Chen, C., Veronese, L., & Yin, Y. (2000). The effects of lamotrigine on the pharmacokinetics of lithium. British Journal of Clinical Pharmacology, 50, 193–195.
Chen, H., Yang, K., Choi, S., Fischer, J. H., & Jeong, H. (2009). Up-regulation of UDP-glucuronosyltransferase (UGT) 1A4 by 17beta-estradiol: a potential mechanism of increased lamotrigine elimination in pregnancy. Drug Metabolism and Disposition, 37, 1841–1847.
Christensen, J., Petrenaite, V., Atterman, J., Sidenius, P., Ohman, I., Tomson, T., et al. (2007). Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial. Epilepsia, 48, 484–489.
Colucci, R., Glue, P., Holt, B., Banfield, C., Reidenberg, P., Meehan, J. W., et al. (1996). Effect of felbamate on the pharmacokinetics of lamotrigine. The Journal of Clinical Pharmacology, 36, 634–638.
Coskun, M., Bozkurt, H., & Zoroglu, S. (2009). Possible lamotrigine-induced mania in a child with autism spectrum disorder and epilepsy (letter). Journal of Clinical Psychopharmacology, 29, 508–509.
Crawford, P., Brown, S., Kerr, M., & Parke Davis Clinical Trials Group. (2001). A randomized open-label study of gabapentin and lamotrigine in adults with learning disability and resistant epilepsy. Seizure, 10, 107–115.
Davanzo, P. A., & King, B. H. (1996). Open trial lamotrigine in the treatment of self-injurious behavior in an adolescent with profound mental retardation. Journal of Child and Adolescent Psychopharmacology, 6, 273–279.
de Leon, J. (2003). Glucuronidation enzymes, genes and psychiatry. The International Journal of Neuropsychopharmacology, 6, 57–72.
de Leon, J., Armstrong, S. C., & Cozza, K. L. (2005). The dosing of atypical antipsychotics. Psychosomatics, 46, 262–273.
Depot, M., Powell, J. R., Messenheimer, J. A., Jr., Cloutier, G., & Dalton, M. J. (1990). Kinetic effects of multiple oral doses of acetaminophen on a single oral dose of lamotrigine. Clinical Pharmacology and Therapeutics, 48, 346–355.
Dixon, R., Job, S., Oliver, R., Tompson, D., Wright, J. G., Maltby, K., et al. (2008). Lamotrigine does not prolong QTc in a thorough QT/QTc study in healthy subjects. British Journal of Clinical Pharmacology, 66, 396–404.
Dolk, H., Jentink, J., Loane, M., Morris, J., de Jong-van den Berg, L. T., & EUROCAT Antiepileptic Drug Working Group. (2008). Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations? Neurology, 71, 714–722.
Doose, D. R., Brodie, M. J., Wilson, E. A., Chadwick, D., Oxbury, J., Berry, D. J., et al. (2003). Topiramate and lamotrigine pharmacokinetics during repetitive monotherapy and combination therapy in epilepsy patients. Epilepsia, 44, 917–922.
Ebert, U., Thong, N. Q., Oertel, R., & Kirch, W. (2000). Effects of rifampicin and cimetidine on pharmacokinetics and pharmacodynamics of lamotrigine in healthy subjects. European Journal of Clinical Pharmacology, 56, 299–304.
Ettinger, A. B., Kustra, R. P., & Hammer, A. E. (2007). Effect of lamotrigine on depressive symptoms in adult patients with epilepsy. Epilepsy & Behavior, 10, 148–154.
Ettinger, A. B., Weisbrot, D. M., Saracco, J., Dhoon, A., Kanner, A., & Devinsky, O. (1998). Positive and negative psychotropic effects of lamotrigine in patients with epilepsy and mental retardation. Epilepsia, 39, 874–877.
Fakhoury, T. A., Barry, J. J., Mitchell Miller, J., Hammer, A. E., & Vuong, A. (2007). Lamotrigine in patients with epilepsy and comorbid depressive symptoms. Epilepsy & Behavior, 10, 155–162.
Fountoulakis, K. N., & Vieta, E. (2008). Treatment of bipolar disorder: a systematic review of available data and clinical perspectives. The International Journal of Neuropsychopharmacology, 11, 999–1029.
Franco, V., Mazzucchelli, I., Gatti, G., Specchio, L. M., La Neve, A., Papantonio, A., et al. (2008). Changes in lamotrigine pharmacokinetics during pregnancy and the puerperium. Therapeutic Drug Monitoring, 30, 544–547.
French, J. A., & Faught, E. (2009). Rational polytherapy. Epilepsia, 50(Suppl 8), 63–68.
Gaffield, M. E., Culwell, K. R., & Lee, C. R. (2011). The use of hormonal contraception among women taking anticonvulsant therapy. Contraception, 83, 16–29.
Gamble, C., Williamson, P. R., Chadwick, D. W., & Marson, A. G. (2006). A meta-analysis of individual patient responses to lamotrigine or carbamazepine monotherapy. Neurology, 66, 1310–1317.
Gamble, C., Williamson, P. R., & Marson, A. G. (2006). Lamotrigine versus carbamazepine monotherapy for epilepsy. The Cochrane Database of Systematic Reviews, 25, CD001031.
Geddes, J. R., Calabrese, J. R., & Goodwin, G. M. (2009). Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. The British Journal of Psychiatry, 194, 4–9.
Ghaemi, S. N. (2009). The failure to know what isn’t known: negative publication bias with lamotrigine and a glimpse inside peer review. Evidence-Based Mental Health, 12, 65–68.
Ghaemi, S. N., Shirzadi, A. A., Filkowski, M. (2008). Publication bias and the pharmaceutical industry: the case of lamotrigine in bipolar disorder. Medscape Journal of Medicine, 10, 211 http://www.medscape.com/viewarticle/579046_1. Accessed 12 Apr 2011.
Gidal, B. E., Walker, J. K., Lott, R. S., Shaw, R., Speth, J., Marty, K. J., et al. (2000). Efficacy of lamotrigine in institutionalized, developmentally disabled patients with epilepsy: A retrospective evaluation. Seizure, 9, 131–136.
GlaxoSmithKline. (2010). Lamictal (lamotrigine) tablets. Lamictal (lamotrigine) chewable dispersible tablets. Lamictal ODT (lamotrigine) orally disintegrating tablets (highlights of prescribing information). Research Triangle Park, NC: GlaxoSmithKline.
GlaxoSmithKline. (2011). Lamictal XR (lamotrigine) extended-release tablets (highlights of prescribing information). Research Triangle Park, NC: GlaxoSmithKline.
Grasela, T. H., Fiedler-Kelly, J., Cox, E., Womble, G. P., Risner, M. E., & Chen, C. (1999). Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy. Journal of Clinical Pharmacology, 39, 373–384.
Gualtieri, C. T., & Johnson, L. G. (2006). Comparative neurocognitive effects of 5 psychotropic anticonvulsants and lithium. Medscape General Medicine, 8, 46.
Hachad, H., Ragueneau-Majlessi, I., & Levy, R. H. (2002). New antiepileptic drugs: review on drug interactions. Therapeutic Drug Monitoring, 24, 91–103.
Harden, C. L. (2008). Antiepileptic drug teratogenesis: what are the risks for congenital malformations and adverse cognitive outcomes? International Review of Neurobiology, 83, 205–213.
Harden, C. L., Pennell, P. B., Koppel, B. S., Hovinga, C. A., Gidal, B., Meador, K. J., et al. (2009). Practice parameter update: management issues for women with epilepsy – focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding. Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology, 73, 126–132.
Harris, E. C., & Barraclough, B. (1997). Suicide as an outcome for mental disorders. A meta-analysis. The British Journal of Psychiatry, 170, 205–228.
Herman, S. T. (2009). Adopting an orphan drug: Rufinamide for Lennox-Gastaut syndrome. Epilepsy Currents, 9, 72–74.
Hesdorffer, D. C., Berg, A. T., & Kanner, A. M. (2010). An update on antiepileptic drugs and suicide: are there definitive answers yet? Epilepsy Currents, 10, 137–145.
Hirsch, L. J., Weintraub, D. B., Buchsbaum, R., Spencer, H. T., Straka, T., Hager, M., et al. (2006). Predictors of lamotrigine-associated rash. Epilepsia, 47, 318–322.
Huber, B., May, T., & Seidel, M. (1998). Lamotrigine in multihandicapped therapy-resistant epileptic patients. Clinical Drug Investigation, 16, 263–277.
Jann, M. W., Hon, Y. Y., Shamsi, S. A., Zheng, J., Awad, E. A., & Spratlin, V. (2006). Lack of pharmacokinetic interaction between lamotrigine and olanzapine in healthy volunteers. Pharmacotherapy, 26, 627–633.
Jefferson, J. W. (2005). Lamotrigine in psychiatry: pharmacology and therapeutics. CNS Spectrums, 10, 224–232.
Johannessen, S. I., & Tomson, T. (2006). Pharmacokinetic variability of newer antiepileptic drugs. When is monitoring needed? Clinical Pharmacokinetics, 45, 1061–1075.
Kalanin, V. V. (2007). Suicidality and antiepileptic drugs. Is there a link? Drug Safety, 30, 123–142.
Kanner, A. M., & Frey, M. (2000). Adding valproate to lamotrigine: a study of their pharmacokinetic interaction. Neurology, 55, 588–591.
Kauffman, K. R., & Gerner, R. (1998). Lamotrigine toxicity secondary to sertraline. Seizure, 7, 163–165.
Kennedy, G. M., & Lhatoo, S. D. (2008). CNS adverse events associated with antiepileptic drugs. CNS Drugs, 22, 739–760.
Kuehn, B. M. (2008). FDA warns of adverse events linked to smoking cessation drug and antiepileptics. The Journal of the American Medical Association, 299, 1121–1122.
Labiner, D. M., Ettinger, A. B., Fakhoury, T. A., Chung, S. S., Shneker, B., Tatum Iv, W. O., et al. (2009). Effects of lamotrigine compared with levetiracetam on anger, hostility, and total mood in patients with partial epilepsy. Epilepsia, 50, 434–442.
Lacy, C. F., Armstrong, L. L., Goldman, M. P., & Lance, L. L. (2009). Drug information handbook (18th ed.). Hudson, OH: Lexi-Comp.
Large, C. H., Di Daniel, E., Li, X., & George, M. S. (2009). Neural network dysfunction in bipolar depression: clues from the efficacy of lamotrigine. Biochemical Society Transactions, 37(Pt 5), 1080–1084.
Levy, R. H., Ragueneau-Majlessi, I., Brodie, M. J., Smith, D. F., Shah, J., & Pan, W. J. (2005). Lack of clinically significant pharmacokinetic interactions between zonisamide and lamotrigine at steady state in patients with epilepsy. Therapeutic Drug Monitoring, 27, 193–198.
Licht, R. W., Nielsen, J. N., Gram, L. F., Vestergaard, P., & Bendz, H. (2010). Lamotrigine versus lithium as maintenance treatment in bipolar I disorder: an open, randomized effectiveness study mimicking clinical practice. The 6th trial of the Danish University Antidepressant Group (DUAG-6). Bipolar Disorders, 12, 483–493.
Linnet, K. (2002). Glucuronidation of olanzapine by cDNA-expressed human UDP-glucuronosyltransferases and human liver microsomes. Human Psychopharmacology, 24, 512–517.
Liston, H. L., Markowitz, J. S., & DeVane, L. (2001). Drug glucuronidation in clinical psychopharmacology. Journal of Clinical Psychopharmacology, 21, 500–515.
Lorberg, B., Youssef, N. A., & Bhagwagar, Z. (2009). Lamotrigine-associated rash: to rechallenge or not to rechallenge? The International Journal of Neuropsychopharmacology, 12, 257–265.
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, 881–886.
Malik, S., Arif, H., & Hirsch, L. J. (2006). Lamotrigine and its applications in the treatment of epilepsy and other neurological and psychiatric disorders. Expert Review of Neurotherapeutics, 6, 1609–1627.
Maniyar, F., Rooney, C., Lily, O., & Bazaz, R. (2009). Anticonvulsant hypersensitivity syndrome presenting as aseptic meningitis. Journal of Neurology, 256, 1190–1191.
Mantegazza, M., Curia, G., Biagini, G., Ragsdale, D. S., & Avoli, M. (2010). Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders. Lancet Neurology, 9, 413–424.
Marcellin, P., de Bony, F., Garret, C., Altman, C., Boige, V., Castelnau, C., et al. (2001). Influence of cirrhosis on lamotrigine pharmacokinetics. British Journal of Clinical Pharmacology, 51, 410–414.
Marson, A. G., Al-Kharusi, A. M., Alwaidh, M., Appleton, R., Baker, G. A., Chadwick, D. W., SANAD Study group, et al. (2007a). The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet, 369, 1016–1026.
Marson, A. G., Al-Kharusi, A. M., Alwaidh, M., Appleton, R., Baker, G. A., Chadwick, D. W., SANAD Study group, et al. (2007b). The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblended randomised controlled trial. Lancet, 369, 1000–1015.
May, T.W., Rambeck, B., Jurgens, U (1999). Influence of oxcarbamazepine and methosuximide on lamotrigine concentrations in epileptic patients with and without valproic acid comedication: results of a retrospective study. Therapeutic Drug Monitoring, 21, 175–181.
May, T. W., Korn-Merker, E., & Rambeck, B. (2003). Clinical pharmacokinetics of oxcarbazepine. Clinical Pharmacokinetics, 42, 1023–1042.
McKee, J. R., Sunder, T. R., FineSmith, R., Vuong, A., Varner, J. A., Hammer, A. E., & Barrett, P. S. (2003). Lamotrigine as adjunctive therapy in patients with refractory epilepsy and mental retardation. Epilepsy & Behavior, 4, 386–394.
Meador, K. J., Baker, G. A., Browning, N., Clayton-Smith, J., Combs-Cantrell, D. T., Cohen, M., NEAD Study Group, et al. (2009). Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. The New England Journal of Medicine, 16(360), 1597–1605.
Merrick, J., Merrick, E., Lunsky, Y., & Kandel, I. (2006). A review of suicidality in persons with intellectual disability. The Israel Journal of Psychiatry and Related Sciences, 43, 258–264.
Messenheimer, J. A. (1998). Rash in adult and pediatric patients treated with lamotrigine. The Canadian Journal of Neurological Sciences, 25, 514–518.
Mockenhaupt, M., Messenheimer, J., Tennis, P., & Schlingmann, J. (2005). Risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptics. Neurology, 64, 1134–1138.
Mockenhaupt, M., Viboud, C., Dunant, A., Naldi, L., Halevy, S., Bouwes Bavinck, J. N., et al. (2008). Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. The Journal of Investigative Dermatology, 128, 35–44.
Mula, M., & Sander, J. W. (2007). Negative effects of antiepileptic drugs on mood in patients with epilepsy. Drug Safety, 30, 555–567.
Newport, D. J., Pennell, P. B., Calamaras, M. R., Ritchie, J. C., Newman, M., Knight, B., et al. (2008). Lamotrigine in breast milk and nursing infants: determination of exposure. Pediatrics, 122, e223–e231.
Nordmo, E., Aronsen, L., Wasland, K., Småbrekke, L., & Vorren, S. (2009). Severe apnea in an infant exposed to lamotrigine in breast milk. The Annals of Pharmacotherapy, 43, 1893–1897.
O’Neill, A., & de Leon, J. (2007). Two case reports of oral ulcers with lamotrigine several weeks after oxcarbazepine withdrawal. Bipolar Disorders, 9, 310–313.
Odishaw, J., & Chen, C. (2000). Effects of steady-state bupropion on the pharmacokinetics of lamotrigine in healthy subjects. Pharmacotherapy, 20, 1448–1453.
Ohman, I., Beck, O., Vitols, S., & Tomson, T. (2008). Plasma concentrations of lamotrigine and its 2-N-glucuronide metabolite during pregnancy in women with epilepsy. Epilepsia, 49, 1075–1080.
Otoul, C., De Smedt, H., & Stockis, A. (2007). Lack of pharmacokinetic interaction of levetiracetam on carbamazepine, valproic acid, topiramate, and lamotrigine in children with epilepsy. Epilepsia, 48, 2111–2115.
Ouellet, G., Tremblay, L., & Marleau, D. (2009). Fulminant hepatitis induced by lamotrigine. Southern Medical Journal, 10, 82–84.
Patsalos, P. N., Berry, D. J., Bourgeois, B. F., Cloyd, J. C., Glauser, T. A., Johannessen, S. I., et al. (2008). Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia, 49, 1239–1276.
Pennell, P. B., Peng, L., Newport, D. J., Ritchie, J. C., Koganti, A., Holley, D. K., et al. (2008). Lamotrigine in pregnancy: clearance, therapeutic drug monitoring, and seizure frequency. Neurology, 70, 2130–2136.
Pisani, F., Oteri, G., Russo, M. F., Di Perri, R., Perucca, E., & Richens, A. (1999). The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction. Epilepsia, 40, 1141–1146.
Punyawudho, B., Ramsay, R. E., Macias, F. M., Rowan, A. J., Collins, J. F., Brundage, R. C., et al. (2008). Population pharmacokinetics of lamotrigine in elderly patients. Journal of Clinical Pharmacology, 48, 455–463.
Ramaratnam, S., Marson, A. G., & Baker, G. A. (2001). Lamotrigine add-on for drug-resistant partial epilepsy. The Cochrane Database of Systematic Reviews, 3, CD001909.
Reimers, A., Helde, G., & Brodtkorb, E. (2005). Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations. Epilepsia, 46, 1414–1417.
Reimers, A., Skogvoll, E., Sund, J. K., & Spigset, O. (2005). Drug interactions between lamotrigine and psychoactive drugs: evidence from a therapeutic drug monitoring service. Journal of Clinical Psychopharmacology, 25, 342–348.
Reinsberger, C., Dorn, T., & Krämer, G. (2008). Smoking reduces serum levels of lamotrigine. Seizure, 17, 651–653.
Rogwaski, M. A., & Löscher, W. (2004). The neurobiology of antiepileptic drugs. Nature Reviews. Neuroscience, 5, 553–564.
Rowland, A., Elliot, D. J., Williams, J. A., Mackenzie, P. I., Dickinson, R. G., & Miners, J. O. (2006). In vitro characterization of lamotrigine N2-glucuronidation and the lamotrigine-valproic acid interaction. Drug Metabolism and Disposition, 34, 1055–1062.
Sachs, G., Bowden, C., Calabrese, J. R., Ketter, T., Thompson, T., White, R., et al. (2006). Effects of lamotrigine and lithium on body weight during maintenance treatment of bipolar I disorder. Bipolar Disorders, 8, 175–181.
Saneto, R. P., & Anderson, G. D. (2009). Onset of action and seizure control in Lennox-Gaustaut syndrome: focus on rufinamide. Therapeutics and Clinical Risk Management, 5, 271–280.
Schieber, F. C., Boulton, D. W., Balch, A. H., Croop, R., Mallikaarjun, S., Benson, J., et al. (2009). A non-randomized study to investigate the effects of the atypical antipsychotic aripiprazole on the steady-state pharmacokinetics of lamotrigine in patients with bipolar I disorder. Human Psychopharmacology, 24, 145–152.
Seo, H. J., Chiesa, A., Lee, S. J., Patkar, A. A., Han, C., Masand, P. S., et al. (2011). Safety and tolerability of lamotrigine: results from 12 placebo-controlled clinical trials and clinical implications. Clinical Neuropharmacology, 34, 39–47.
Sharma, C., Dubey, R., Kumar, H., & Saha, N. (2005). Food reduces the bioavailability of lamotrigine. The Indian Journal of Medical Research, 121, 659–664.
Shor, S., Koren, G., & Nulman, I. (2007). Teratogenicity of lamotrigine. Canadian Family Physician, 53, 1007–1009.
Sidhu, J., Job, S., Bullman, J., Francis, E., Abbott, R., & Ascher, J. G. (2006). Pharmacokinetics and tolerability of lamotrigine and olanzapine coadministered to healthy subjects. British Journal of Clinical Pharmacology, 61, 420–426.
Sidhu, J., Job, S., Singh, S., & Philipson, R. (2006). The pharmacokinetic and pharmacodynamic consequences of the co-administration of lamotrigine and a combined oral contraceptive in healthy female subjects. British Journal of Clinical Pharmacology, 61, 191–199.
Simister, R. J., Sander, J. W., & Koepp, M. J. (2007). Long-term retention rates of new antiepileptic drugs in adults with chronic epilepsy and learning disability. Epilepsy & Behavior, 2, 336–339.
Sirven, J. I., Fife, T. D., Wingerchuk, D. M., & Drazkowski, J. F. (2007). Second-generation antiepileptic drugs’ impact on balance: a meta-analysis. Mayo Clinic Proceedings, 82, 40–47.
Spina, E., D’Arrigo, C., Migliardi, G., Santoro, V., Muscatello, M. R., Micò, U., et al. (2006). Effect of adjunctive lamotrigine treatment on the plasma concentrations of clozapine, risperidone and olanzapine in patients with schizophrenia or bipolar disorder. Therapeutic Drug Monitoring, 28, 599–602.
Spina, E. A., & de Leon, J. (2007). Metabolic drug interactions with newer antipsychotics: a comparative review. Basic & Clinical Pharmacology & Toxicology, 100, 4–22.
Spina, E., Santoro, V., & D’Arrigo, C. (2008). Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update. Clinical Therapeutics, 30, 1206–1227.
Stafstrom, C. E. (2009). Update on the management of Lennox-Gastaut syndrome with a focus on rufinamide. Neuropsychiatric Disease and Treatment, 5, 547–551.
Steinbaugh, L., & Szaflarski, J. P. (2010). Adjunctive therapy for the treatment of primary generalized tonic-clonic seizures: focus on once-daily lamotrigine. Drug Design, Development and Therapy, 4, 337–342.
Subuh Surja, A. A., Brotzge, K. E., & El-Mallakh, R. S. (2005). Serious rash with lamotrigine after carbamazepine discontinuation: a case report (letter). The Journal of Clinical Psychiatry, 66, 400–401.
Sunder, T. R., McKee, J. R., Hammer, A. E., & Vuongc, A. (2006). Efficacy and tolerability of adjunctive lamotrigine for refractory epilepsy in institutional or community residents with mental retardation. Current Medical Research and Opinion, 22, 693–702.
Suppes, T., Dennehy, E. B., Swann, A. C., Bowden, C. L., Calabrese, J. R., Hirschfeld, R. M., Texas consensus conference panel on medication treatment of bipolar disorder, et al. (2002). Report of the Texas consensus conference panel on medication treatment of bipolar disorder 2000. The Journal of Clinical Psychiatry, 63, 288–299.
Tengstrand, M., Star, K., van Puijenbroek, E. P., & Hill, R. (2010). Alopecia in association with lamotrigine use: an analysis of individual case safety reports in a global database. Drug Safety, 33, 653–658.
Theis, J. G., Sidhu, J., Palmer, J., Job, S., Bullman, J., & Ascher, J. (2005). Lack of pharmacokinetic interaction between oxcarbazepine and lamotrigine. Neuropsychopharmacology, 30, 2269–2274.
Thibert, R. L., Conant, K. D., Braun, E. K., Bruno, P., Said, R. R., Nespeca, M. P., et al. (2009). Epilepsy in angelman syndrome: a questionanaire-based assessment of the natural history and current treatment options. Epilepsia, 50, 2369–2376.
Thomas, S. P., Nandhra, H. S., & Jayaraman, A. (2010). Systematic review of lamotrigine augmentation of treatment resistant unipolar depression (TRD). Journal of Mental Health, 19, 168–175.
Tiihonen, J., Wahlbeck, K., & Kiviniemi, V. (2009). The efficacy of lamotrigine in clozapine-resistant schizophrenia: a systematic review and meta-analysis. Schizophrenia Research, 109, 10–14.
Titlic, M., Jukic, I., Tonkic, A., Josipovic-Jelic, Z., Boschi, V., Mihalj, M., et al. (2008). Lamotrigine in the treatment of pain syndromes and neuropathic pain. Bratislavské Lekárske Listy, 109, 421–424.
Tjia-Leong, E., Leong, K., & Marson, A. G. (2010). Lamotrigine adjunctive therapy for refractory generalized tonic-clonic seizures. The Cochrane Database of Systematic Reviews, 12, CD007783.
Tomson, T. (2009). Which drug for the pregnant woman with epilepsy? The New England Journal of Medicine, 360, 1667–1669.
Tomson, T., Luef, G., Sabers, A., Pittschieler, S., & Ohman, I. (2006). Valproate effects on kinetics of lamotrigine in pregnancy and treatment with oral contraceptives. Neurology, 67, 1297–1299.
Tomson, T., Lukic, S., & Ohman, I. (2010). Are lamotrigine kinetics altered in menopause? Observations from a drug monitoring database. Epilepsy & Behavior, 19, 86–88.
US Department of Mental Health and Human Services (2008). Statistical review and evaluation: antiepileptic drugs and suicidality. http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4372b1-01-FDA.pdf. Accessed 5 Apr 2011.
Vajda, F. J., Graham, J. E., Hitchcock, A. A., O’Brien, T. J., Lander, C. M., & Eadie, M. J. (2010). Is lamotrigine a significant human teratogen? Observations from the Australian Pregnancy Register. Seizure, 19, 558–561.
van der Lee, M. J., Dawood, L., ter Hofstede, H. J., de Graaff-Teulen, M. J., van Ewijk-Beneken Kolmer, E. W., Caliskan-Yassen, N., et al. (2006). Lopinavir/ritonavir reduces lamotrigine plasma concentrations in healthy subjects. Clinical Pharmacology and Therapeutics, 80, 159–168.
van der Loos, M. L., Mulder, P. G., Hartong, E. G., Blom, M. B., Vergouwen, A. C., de Keyzer, H. J., LamLit Study Group, et al. (2009). Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter double-blind placebo-controlled trial. The Journal of Clinical Psychiatry, 70, 223–231.
Vigo, D. V., & Baldessarini, R. J. (2009). Anticonvulsants in the treatment of major depressive disorder: an overview. Harvard Review of Psychiatry, 17, 231–241.
Warren, Z. E., Sanders, K. B., & Veenstra-VanderWeele, J. (2010). Identity crisis involving body image in a young man with autism. The American Journal of Psychiatry, 167, 1299–1303.
Wegner, I., Edelbroek, P. M., Bulk, S., & Lindhout, D. (2009). Lamotrigine kinetics within the menstrual cycle, after menopause, and with oral contraceptives. Neurology, 73, 1388–1393.
Weintraub, D., Buchsbaum, R., Resor, S. R., Jr., & Hirsch, L. J. (2005). Effect of antiepileptic drug comedication on lamotrigine clearance. Archives of Neurology, 62, 1432–1436.
Weintraub, D., Buchsbaum, R., Resor, S. R., Jr., & Hirsch, L. J. (2007). Psychiatric and behavioral side effects of the newer antiepileptic drugs in adults with epilepsy. Epilepsy & Behavior, 10, 105–110.
Wiffen, P. J., Derry, S., & Moore, R. A. (2011). Lamotrigine for acute and chronic pain. The Cochrane Database of Systematic Reviews, 2, CD006044.
Wong, I. C. K., Mawer, G. E., & Sander, J. W. (1999). Factors influencing the incidence of lamotrigine-related skin rash. The Annals of Pharmacotherapy, 33, 1037–1042.
Working Group of the International Association of the Scientific Study of Intellectual Disability. (2001). Clinical guidelines for the management of epilepsy in adults with an intellectual disability. Seizure, 10, 401–409.
Zaatreh, M. M. (2003). Anticonvulsant-induced dyskinesia. Expert Opinion on Drug Safety, 2, 385–393.
Zaccara, G., Gangemi, P. F., & Cincotta, M. (2008). Central nervous system adverse effects of new antiepileptic drugs. A meta-analysis of placebo-controlled studies. Seizure, 17, 405–421.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Appendix Drug Utilization Review: Lamotrigine
Appendix Drug Utilization Review: Lamotrigine
DRUG UTILIZATION REVIEW CRITERIA | CRITERIA MET | |||||
|---|---|---|---|---|---|---|
LAMOTRIGINE FOR ADULTS WITH IDs | YES | NO | NA | |||
1) Indication: Check one of the following indications for use | ||||||
| Epilepsy, including monotherapy and adjunctive therapy in partial onset seizures, primary generalized tonic–clonic seizures and Lennox–Gastaut syndrome. | |||||
| Maintenance treatment of bipolar I disorder. (If used beyond 18 months, long-term usefulness is reevaluated.) | |||||
| Other: Specify_________________________. When lamotrigine is used for off-label indications, the chart will specifically include an explanatory note (Y___ N___). | |||||
To meet indication criteria at least one indication is present | | | ||||
2) Dose: Formulation: Dose and pattern: | ||||||
The daily dose was divided in two for conventional formulations (Y__ N__) or justification was provided (Y__). | | | | |||
Extended release tablets were administered once a day (Y__ N__) or justification was provided (Y__). When the extended release tablets are used for bipolar disorder, the possible need for higher maintenance dose is documented in the chart (Y__ N__). The extended release tablets are not crushed or chewed (Y__ N__). | | | | |||
Patients with epilepsy taking valproate and NO inducers: The initial dose was ≤ 25 mg every other day for weeks 1 and 2, and 25 mg every day for weeks 3 and 4 (Y__ N__). After that, the dose was increased by 25–50 mg/day every 1–2 weeks to reach maintenance level (Y__ N__) unless otherwise recommended by consultant with expertise in the area (Y__). | | | | |||
Patients with epilepsy taking valproate and NO inducers: The maintenance dosage ranges between 100 and 200 mg/day for conventional formulations or 200–250 mg/day for extended release tablets (Y__ N__) unless otherwise recommended by consultant with expertise in the area (Y__). | | | | |||
Patients with epilepsy NOT taking enzyme-inducing antiepileptic drugs or other inducers and NOT taking valproate: The initial dose was ≤ 25 mg every day for weeks 1 and 2; and 50 mg/day in two divided doses for weeks 3 and 4 (Y__ N__). After that, the dose was increased ≤ 50 mg/day every 1–2 weeks to reach maintenance level (Y__ N__) unless otherwise recommended by consultant with expertise in the area (Y__). | | | | |||
Patients with epilepsy NOT taking enzyme-inducing antiepileptic drugs or other inducers and NOT taking valproate: The maintenance doses ranged between 225 and 375 mg/day for conventional formulations (Y__ N__) or 300–400 mg/day for extended release tablets (Y__ N__) unless otherwise recommended by consultant with expertise in the area (Y__). | | | | |||
Patients with epilepsy taking enzyme-inducing antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, and primidone) or other inducers (rifampicin and estrogen-containing oral contraceptives) and NO valproate: The initial dose was ≤ 50 mg every day for weeks 1 and 2; and 100 mg/day in two divided doses for weeks 3 and 4 (Y__ N__). After that, dose was increased by ≤ 100 mg/day every 1–2 weeks to reach maintenance level (Y__ N__) unless otherwise recommended by consultant with expertise in the area (Y__). | | | | |||
Patients with epilepsy taking enzyme-inducing antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, and primidone) or other inducers (rifampicin and estrogen-containing oral contraceptives) and NO valproate: The maintenance dosage ranges between 300 and 500 mg/day for conventional formulations (Y__ N__) or 400–600 mg/day for extended release tablets (Y__ N__) unless otherwise recommended by consultant with expertise in the area (Y__). | | | | |||
Patients with bipolar disorder taking valproate. The initial dose was ≤ 25 mg every other day for weeks 1 and 2 (Y__ N__); ≤ 25 mg daily for weeks 3 and 4 (Y__ N__); ≤ 50 mg daily for week 5 (Y__ N__); and ≤100 mg daily for weeks 6 and 7 (Y__ N__) or justification was provided (Y__). | | | | |||
Patients with bipolar disorder taking valproate. The maintenance dose is ≤100 mg/day for conventional formulations (Y__ N__) or justification was provided (Y__). | | | | |||
Patients with bipolar disorder taking enzyme-inducing drugs and NOT taking valproate. The initial dose was ≤ 50 mg daily for weeks 1 and 2 (Y__ N__); ≤ 100 mg daily in divided doses for weeks 3 and 4 (Y__ N__); ≤ 200 mg daily in divided doses for week 5 (Y__ N__); ≤ 300 mg daily in divided doses for week 6 (Y__ N__); and ≤ 400 mg daily in divided doses for week 7 (Y__ N__) or justification was provided (Y__). | | | | |||
Patients with bipolar disorder taking enzyme-inducing drugs and NOT taking valproate. The maintenance dose is ≤ 400 mg/day for conventional formulations (Y__ N__) or justification was provided (Y__). | | | | |||
Patients with bipolar disorder NOT taking enzyme-inducing drugs and NOT taking valproate. The initial dose was ≤ 25 mg daily for weeks 1 and 2 (Y__ N__); ≤ 50 mg daily for weeks 3 and 4 (Y__ N__); ≤ 100 mg daily for week 5 (Y__ N__); and ≤ 200 mg daily for weeks 6 and 7 (Y__ N__) or justification was provided (Y__). | | | | |||
Patients with bipolar disorder NOT taking enzyme-inducing drugs and NOT taking valproate. The maintenance dose is ≤ 200 mg/day for conventional formulations (Y__ N__) or justification was provided (Y__). | | | | |||
Taking phenytoin__, carbamazepine__, phenobarbital__, primidone__, rifampicin__, lopinavir/ritonavir__, oral contraceptives__, other inducer (specify)____________. The chart documents the interaction (Y___ N___). The dosage of lamotrigine may need to be increased when any of these antiepileptic drugs are added, and the discontinuation of any of these inducers may need to be followed by a decrease in lamotrigine dosage. | | | | |||
Taking acetaminophen regularly___. The chart documents the possibility of an interaction (Y___ N___). A limited study indicated that acetaminophen may induce lamotrigine metabolism. | | | | |||
Taking valproate__. The chart documents the interaction (Y___ N___). The dosage of lamotrigine may need to be decreased when valproate is added, and the discontinuation of valproate may need to be followed by an increase in lamotrigine dosage. | | | | |||
Taking carbamazepine__ and having high carbamazepine levels (>8 mg/L). The chart documents the interaction and close monitoring of adverse drug reactions (ADRs) (Y___ N___). | | | | |||
Hepatic___, or renal___ impairment or age ≥ 65 years old ___. The chart documents that dosing accounted for them (Y___ N___). | | | | |||
Pregnancy is associated with an increase in lamotrigine metabolism. Monthly lamotrigine levels are measured (Y___ N___). | | | | |||
To meet dose criteria all are Yes or NA. | | | ||||
3) Relative contraindications: Check any present | ||||||
| Pregnancy (Category C) or breastfeeding. | |||||
| Hypersensitivity to other antiepileptics, including carbamazepine, phenytoin, phenobarbital, and oxcarbazepine. | |||||
| Prior skin rash on lamotrigine with no systemic symptoms. The chart documents not only risk-benefit but literature has been reviewed (Y___ N___) and an expert has been consulted (Y___ N___). | |||||
| Hepatic impairment. | |||||
| Renal function impairment. | |||||
If any of the above are checked, rationale is documented in chart to meet relative contraindication criteria. If none are present check NA. | | | | |||
4) Baseline monitoring studies: | ||||||
| Skin exam. | |||||
| Complete blood count (CBC) with differential. | |||||
| Basic metabolic panel___ and liver function tests___. | |||||
| Serum concentrations of concomitantly administered antiepileptics which are usually followed by therapeutic drug monitoring. | |||||
Answer Yes (all completed) or No. If information is not available check NA. | | | | |||
5) Discontinuation: | ||||||
Lamotrigine is or was withdrawn slowly to minimize the potential of increased seizure frequency (Y___ N___). Abrupt withdrawal was justified by a major medical reason (Y___ N___). | | | | |||
6) ADRs due to lamotrigine: Check left boxes to indicate which ADRs are present | ||||||
6.1) Common ADRs: | ||||||
| CNS: including ataxia, dizziness, diplopia, or headaches. | | Nausea. | |||
6.2) Relatively uncommon ADRs: | ||||||
| Other neurological or psychiatric, including cognitive impairment, psychiatric symptoms or movement disorders. Specify_________________ | | Benign skin rash. | |||
| Other____________ | | Other__________ | |||
6.3) Potentially lethal ADRs: | ||||||
| Stevens–Johnson syndrome/toxic epidermal necrolysis. | | Other hypersensitivity reactions, including hypersensitivity hepatitis or aseptic meningitis | |||
| Other____________ | | Suicidal ideation or behavior. | |||
Answer Yes (intervention or benefit/risk discussion after ADRs developed) or No (neither intervention nor benefit/risk discussion after ADRs developed) or NA (no abnormality developed). | | | | |||
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
de Leon, J. (2012). A Practitioner’s Guide to Prescribing Lamotrigine for Adults with Intellectual Disabilities. In: de Leon, J. (eds) A Practitioner's Guide to Prescribing Antiepileptics and Mood Stabilizers for Adults with Intellectual Disabilities. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-2012-5_9
Download citation
DOI: https://doi.org/10.1007/978-1-4614-2012-5_9
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4614-2011-8
Online ISBN: 978-1-4614-2012-5
eBook Packages: MedicineMedicine (R0)