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Lamotrigine

A Review of its Use in Bipolar Disorder

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Summary

Abstract

Lamotrigine (Lamictal®), a phenyltriazine derivative, is a well established anticonvulsant agent that has shown efficacy in the prevention of mood episodes in adult patients with bipolar I disorder. The mechanism of action of the drug in patients with bipolar disorder may be related to the inhibition of sodium and calcium channels in presynaptic neurons and subsequent stabilisation of the neuronal membrane.

Lamotrigine monotherapy significantly delayed time to intervention with additional pharmacotherapy or electroconvulsive therapy for any new mood episode (mania, hypomania, depression and mixed episodes), compared with placebo, in two large, randomised, double-blind trials of 18 months’ duration. Additionally, lamotrigine was significantly superior to placebo at prolonging time to intervention for depression. These effects of lamotrigine were demonstrated in both recently manic/hypomanic and recently depressed patients. Lamotrigine showed efficacy in delaying manic/hypomanic episodes in pooled data only, although lithium was superior to lamotrigine on this measure.

Two of four double-blind, short-term studies have shown lamotrigine to be more effective than placebo in the treatment of patients with treatment-refractory bipolar disorder or those with bipolar depression. Lamotrigine has not demonstrated efficacy in the treatment of acute mania.

Lamotrigine was generally well tolerated in maintenance studies with the most common adverse events being headache, nausea, infection and insomnia. Incidences of diarrhoea and tremor were significantly lower in lamotrigine-than in lithium-treated patients. The incidence of serious rash with lamotrigine treatment was 0.1% in all studies of bipolar disorder and included one case of mild Stevens-Johnson syndrome. Lamotrigine did not appear to cause bodyweight gain.

The dosage of lamotrigine is titrated over a 6-week period to 200 mg/day to minimise the incidence of serious rash. Adjustments to the initial and target dosages are required if coadministered with valproate semisodium or carbamazepine.

Conclusion: Lamotrigine has been shown to be an effective maintenance therapy for patients with bipolar I disorder, significantly delaying time to intervention for any mood episode. Additionally, lamotrigine significantly delayed time to intervention for a depressive episode and showed limited efficacy in delaying time to intervention for a manic/hypomanic episode, compared with placebo. Although not approved for the short-term treatment of mood episodes, lamotrigine has shown efficacy in the acute treatment of patients with bipolar depression but has not demonstrated efficacy in the treatment of acute mania. Lamotrigine is generally well tolerated, does not appear to cause bodyweight gain and, unlike lithium, generally does not require monitoring of serum levels.

Pharmacodynamic Properties

Lamotrigine is a phenyltriazine derivative. The mechanism of action of the drug in the treatment of patients with bipolar disorder is not fully understood, but may be related to the inhibition of sodium and calcium channels in presynaptic neurons and subsequent stabilisation of the neuronal membrane. In addition, lamotrigine has demonstrated neuroprotective effects in animal models. Lamotrigine lacks appreciable in vitro affinity for dopaminergic, adrenergic, muscarinic, opioid and adenosine receptors at clinically relevant concentrations, but binds weakly to serotonin 5HT3 receptors. It also down-regulates cortical 5HT1A receptor-mediated adenyl cyclase responses in an animal model.

Normal synaptic conduction is unaffected by lamotrigine, which suppresses abnormal (sustained repetitive) firing of sodium-dependent action potentials in animal models.

Early studies in patients with epilepsy who received lamotrigine indicated a propensity for improved mood, which led to controlled clinical trials in patients with bipolar disorder. Lamotrigine has minimal effects on psychomotor, cognitive and memory function and appears not to be associated with sedative effects or bodyweight gain.

Pharmacokinetic Properties

Oral lamotrigine is readily bioavailable (98%), and undergoes minimal first-pass metabolism. Absorption of lamotrigine is unaffected by food. Linear pharmacokinetics show peak lamotrigine concentrations occurring 1–3 hours after a dose. Mean protein binding is 55–68% and the drug is widely distributed to all organs and tissues, including brain tissue. It also crosses the placenta and is found in the fetus and in breast milk. Lamotrigine is extensively metabolised in the liver, predominantly via N-glucuronidation (the rate-limiting step in elimination of the drug). Clearance is 1.6–2.6 L/h and the mean plasma elimination half-life is 25–35 hours.

Drug Interactions

Lamotrigine pharmacokinetics appear not to be significantly altered by many commonly used psychotropic agents, nor does lamotrigine alter the pharmacokinetics of lithium. However, enzyme-inhibiting drugs (e.g. valproate semi-sodium) increase lamotrigine plasma concentrations and enzyme-inducing drugs (e.g. carbamazepine) decrease lamotrigine concentrations. Lamotrigine appears not to have clinically significant reciprocal effects on the pharmacokinetics of these drugs.

Therapeutic Efficacy

Lamotrigine has been shown to be an effective maintenance treatment in patients with bipolar I disorder who have had a recent depressive or manic/hypomanic episode. Data from two placebo-controlled, double-blind, 18-month comparative studies showed that lamotrigine (100–400 mg/day) or lithium (dose titrated to a serum level of 0.8–1.1 mEq/L) each significantly delayed the time to intervention with additional pharmacotherapy or electroconvulsive therapy for an emerging mood episode compared with placebo (p < 0.05 for lamotrigine vs placebo and for lithium vs placebo in both studies). In addition, both studies showed that lamotrigine, but not lithium, was significantly superior to placebo at prolonging time to intervention for a depressive mood episode. Similarly lithium, but not lamotrigine, was significantly better than placebo at delaying time to intervention for an emerging manic/hypomanic episode. However, in pooled data lamotrigine also significantly delayed time to intervention for a manic/hypomanic episode, although lithium was superior to lamotrigine on this measure.

Lamotrigine was shown to be more effective than placebo in the treatment of patients with treatment-refractory bipolar disorder or those with bipolar depression in two of four double-blind short-term studies. Lamotrigine has not demonstrated efficacy in the treatment of acute mania.

Tolerability

Lamotrigine 100–400 mg/day as monotherapy was generally well tolerated in two maintenance trials in patients with bipolar I disorder, with a similar adverse event profile to that of placebo. The most common adverse events were headache (19%), nausea (14%), infection (13%) and insomnia (10%). Significantly fewer lamotrigine recipients, compared with those receiving lithium, reported diarrhoea and tremor. The incidence of adverse events was similar in patients who received lamotrigine dosages of 50 mg/day compared with those who received 200 mg/day.

Maintenance therapy with lamotrigine did not appear to increase bodyweight after 52 weeks’ treatment. Obese patients (body mass index ≥30 kg/m2) receiving lamotrigine lost an average 2.96kg, whereas those who received lithium or placebo gained 3.3 and 1.46kg, respectively.

In a meta-analysis of eight randomised, double-blind, placebo-controlled trials in patients with bipolar disorder, serious adverse events occurred at a similar rate in patients receiving lamotrigine (8%), lithium (8%) and placebo (7%). Induction of mania was the most common serious adverse event and occurred in 3% of patients in each treatment group.

The incidence of suicide per year in the meta-analysis was similar between patients receiving lamotrigine and placebo (0.7% vs 0.6%) while no suicides occurred among lithium recipients. Suicide attempts occurred at a similar rate per year in both lamotrigine (1.8%) and placebo (1.1%) recipients. Sexual problems were reported in <1% of patients receiving lamotrigine.

Three of 2272 (0.1%) patients receiving lamotrigine in all controlled and uncontrolled bipolar disorder studies developed a serious rash, including one case of mild Stevens-Johnson syndrome, which was reported in a patient while receiving adjunctive lamotrigine during an open-label phase. The patient did not require hospitalisation and recovered uneventfully.

Dosage and Administration

Lamotrigine is approved in the US for the maintenance treatment of adults with bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania and mixed episodes) in patients treated for acute mood episodes with standard therapy.

The initial recommended monotherapy dosage is 25 mg/day orally which is gradually increased to 200 mg/day over 6 weeks. Dosages over 200 mg/day as monotherapy are not recommended, as no additional efficacy has been demonstrated in clinical trials evaluating dosages up to 400 mg/day. For patients taking valproate semisodium, the initial recommended lamotrigine dosage is 25mg every other day and the target dosage is 100 mg/day from week 6. In recipients of carbamazepine (or other enzyme-inducing drugs), the initial recommended lamotrigine dosage is 50 mg/day, which is gradually increased up to 400 mg/day from week 7. Dosages ≥50 mg/day can be given once-daily or as two divided doses. There are no formal recommendations as to the duration of maintenance therapy in bipolar I disorder. Lamotrigine should be gradually discontinued over a period of at least 2 weeks.

The risk of serious rash, including Stevens-Johnson syndrome, may be increased by coadministration of lamotrigine with valproate semisodium, by exceeding the recommended initial lamotrigine dosage or by exceeding the recommended dosage titration. Lamotrigine should be discontinued at the first sign of any rash, unless the rash is clearly not drug-related.

Reduced maintenance dosages are recommended for patients with hepatic impairment.

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References

  1. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Arch Gen Psychiatry 1994; 51: 8–19

    Article  PubMed  CAS  Google Scholar 

  2. Regier DA, Narrow WE, Rae DS, et al. The de facto US mental and addictive disorders service system: epidemiologic catchment area prospective 1-year prevalence rates of disorders and services. Arch Gen Psychiatry 1993; 50: 85–94

    Article  PubMed  CAS  Google Scholar 

  3. Malhi GS, Mitchell PB, Salim S. Bipolar depression: management options. CNS Drugs 2003; 17(1): 9–25

    Article  PubMed  CAS  Google Scholar 

  4. Hirschfeld RMA, Bowden CL, Gitlin MJ, et al. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002 Apr; 159 (4 Suppl.): 1–50

    Article  Google Scholar 

  5. Cusin C, Serretti A, Lattuada E, et al. Impact of clinical variables on illness time course in mood disorders. Psychiatry Res 2000; 97: 217–27

    Article  PubMed  CAS  Google Scholar 

  6. Judd LL, Akiskal HS, Schettler PJ, et al. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 2002 Jun; 59: 530–7

    Article  PubMed  Google Scholar 

  7. Simpson SG, Jamison KR. The risk of suicide in patients with bipolar disorders. J Clin Psychiatry 1999; 60 Suppl. 2: 53–6

    PubMed  Google Scholar 

  8. Jamison KR. Suicide and bipolar disorder. J Clin Psychiatry 2000; 61 Suppl. 9: S47–51

    Google Scholar 

  9. Tondo L, Baldessarini RJ. Reduced suicide risk during lithium maintenance treatment. J Clin Psychiatry 2000; 61 Suppl. 9: 97–104

    PubMed  CAS  Google Scholar 

  10. Bowden CL. Lamotrigine in the treatment of bipolar disorder. Expert Opin Pharmacother 2002 Oct; 3(10): 1513–9

    Article  PubMed  CAS  Google Scholar 

  11. 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. In press

  12. 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 Apr; 60(4): 392–400

    Article  PubMed  CAS  Google Scholar 

  13. Goa KL, Ross SR, Chrisp P, et al. Lamotrigine: a review of its pharmacological properties and clinical efficacy in epilepsy. Drugs 1993; 46(1): 152–76

    Article  PubMed  CAS  Google Scholar 

  14. Fitton A, Goa KL. Lamotrigine: an update of its pharmacology and therapeutic use in epilepsy. Drugs 1995 Oct; 50: 691–713

    Article  PubMed  CAS  Google Scholar 

  15. Culy CR, Goa KL. Lamotrigine: a review of its use in childhood epilepsy. Paediatr Drugs 2000 Jul; 2(4): 299–330

    Article  PubMed  CAS  Google Scholar 

  16. Videbech P. MRI findings in patients with affective disorder: a meta-analysis. Acta Psychiatr Scand 1997; 96: 157–68

    Article  PubMed  CAS  Google Scholar 

  17. Li X, Ketter TA, Frye MA. Synaptic, intracellular, and neuroprotective mechanisms of anticonvulsants: are they relevant for the treatment and course of bipolar disorders? J Affect Disord 2002 May; 69(1–3): 1–14

    Article  PubMed  CAS  Google Scholar 

  18. Leach MJ, Marden CM, Miller AA, et al. Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action. Epilepsia 1986; 27(5): 490–7

    Article  PubMed  CAS  Google Scholar 

  19. Stefani A, Spadoni F, Siniscalchi A, et al. Lamotrigine inhibits Ca2+ currents in cortical neurons: functional implications. Eur J Pharmacol 1996; 307: 113–6

    Article  PubMed  CAS  Google Scholar 

  20. Wang S-J, Huang C-C, Hsu K-S, et al. Inhibition of N-type calcium currents by lamotrigine in rat amygdalar neurones. Neuroreport 1996; 7: 3037–40

    Article  PubMed  CAS  Google Scholar 

  21. von Wegerer J, Hesslinger B, Berger M, et al. A calcium antagonistic effect of the new antiepileptic drug lamotrigine. Eur Neuropsychopharmacol 1997 May; 7(2): 77–81

    Article  Google Scholar 

  22. Grunze H, Greene RW, Möller H-J, et al. Lamotrigine may limit pathological excitation in the hippocampus by modulating a transient potassium outward current. Brain Res 1998; 791: 330–4

    Article  PubMed  CAS  Google Scholar 

  23. Siniscalchi A, Zona C, Guatteo E, et al. An electrophysiological analysis of the protective effects of felbamate, lamotrigine, and lidocaine on the functional recovery from in vitro ischemia in rat neocortical slices. Synapse 1998 Dec; 30(4): 371–9

    Article  PubMed  CAS  Google Scholar 

  24. Leach MJ, Baxter MG, Critchley MAE, et al. Neurochemical and behavioral aspects of lamotrigine. Epilepsia 1991; 32 Suppl 2: S4–8

    Article  PubMed  CAS  Google Scholar 

  25. Rataud J, Debarnot F, Mary V, et al. Comparative study of voltage-sensitive sodium channel blockers in focal ischaemia and electric convulsions in rodents. Neurosci Lett 1994; 172: 19–23

    Article  PubMed  CAS  Google Scholar 

  26. Shuaib A, Mahmood RH, Wishart T, et al. Neuroprotective effects of lamotrigine in global ischemia in gerbils. A histological, in vivo microdialysis and behavioral study. Brain Res 1995; 702: 199–206

    CAS  Google Scholar 

  27. Smith SE, Meldrum BS. Cerebroprotective effect of lamotrigine after focal ischemia in rats. Stroke 1995; 26: 117–22

    Article  PubMed  CAS  Google Scholar 

  28. Wiard RP, Dickerson MC, Beek O, et al. Neuroprotective properties of the novel antiepileptic lamotrigine in a gerbil model of global cerebral ischemia. Stroke 1995; 26: 466–72

    Article  PubMed  CAS  Google Scholar 

  29. Casanovas A, Ribera J, Hukkanen M, et al. Prevention by lamotrigine, MK-801 and Nw-nitro-L-arginine methyl ester of motoneuron cell death after neonatal axotomy. Neuroscience 1996; 71(2): 313–25

    Article  PubMed  CAS  Google Scholar 

  30. Schulz JB, Matthews RT, Henshaw DR, et al. Neuroprotective strategies for treatment of lesions produced by mitochondrial toxins: implications for neurodegenerative diseases. Neuroscience 1996; 71(4): 1043–8

    Article  PubMed  CAS  Google Scholar 

  31. Adams J, Collaço-Moraes Y, de Belleroche J, et al. Cyclooxy-genase-2 induction in cerebral cortex: an intracellular response to synaptic excitation. J Neurochem 1996; 66: 6–13

    Article  PubMed  CAS  Google Scholar 

  32. McGeer EG, Zhu SG. Lamotrigine protects against kainate but not ibotenate lesions in rat striatum. Neurosci Lett 1990; 112: 348–51

    Article  PubMed  CAS  Google Scholar 

  33. Prescribing information: Lamictal® (lamotrigine) [online]. Available from URL: http://us.gsk.com/products/assets/us_lamictal.pdf [Accessed 2003 Jun 25]

  34. Southam E, Kirkby D, Higgins GA, et al. Lamotrigine inhibits monoamine uptake in vitro and modulates 5-hydroxy-tryptamine uptake in rats. Eur J Pharmacol 1998 Sep 25; 358(1): 19–24

    Article  PubMed  CAS  Google Scholar 

  35. Vinod KY, Subhash MN. Lamotrigine induced selective changes in 5-HT1a receptor mediated response in rat brain. Neurochem Int 2002 Apr; 40(4): 315–9

    Article  PubMed  CAS  Google Scholar 

  36. Shiah I-S, Yatham LN, Lam RW. Effects of lamotrigine on the 5-HT1a receptor function in healthy human males. J Affect Disord 1998 May; 49(2): 157–62

    Article  PubMed  CAS  Google Scholar 

  37. Xie X, Hagan RM. Cellular and molecular actions of lamotrigine: possible mechanisms of efficacy in bipolar disorder. Neuropsychobiology 1998 Oct; 38(3): 119–30

    Article  PubMed  CAS  Google Scholar 

  38. Smith D, Chadwick D, Baker G, et al. Seizure severity and the quality of life. Epilepsia 1993; 34 Suppl. 5: S31–5

    Article  PubMed  Google Scholar 

  39. Smith D, Baker G, Davies G, et al. Outcomes of add-on treatment with lamotrigine in partial epilepsy. Epilepsia 1993; 34(2): 312–22

    Article  PubMed  CAS  Google Scholar 

  40. Jacoby A, Baker G, Bryant-Comstock L, et al. Lamotrigine add-on therapy is associated with improvement in mood in patients with severe epilepsy [abstract no. 1.4]. Epilepsia 1996; 37 Suppl. 5: 202

    Google Scholar 

  41. Harden C, Lazar LM, Pick LH, et al. Effect of lamotrigine on mood in adult epilepsy patients [abstract no. P02.052]. Neurology 1998; 50 (4 Suppl. 4): A102

    Google Scholar 

  42. Mervaala E, Koivisto K, Hänninen T, et al. Electrophysiological and neuropsychological profiles of lamotrigine in young and age-associated memory impairment (AAMI) subjects [abstract no. 357P]. Neurology 1995; 45 Suppl. 4: A259

    Google Scholar 

  43. Cohen AF, Ashby D, Crowley G, et al. Lamotrigine (BW430C), a potential anticonvulsant. Effects on the central nervous system in comparison with phenytoin and diazepam. Br J Clin Pharmacol 1985; 20: 619–29

    Article  PubMed  CAS  Google Scholar 

  44. Ginsberg L, Sachs G, KetterT, et al. Effects of mood stabilizers on body weight in bipolar I disorder [abstract no. NR463 plus poster]. American Psychiatric Association 2003 Annual Meeting — new research abstracts; 2003 May 17; San Francisco (CA), 173–4

  45. Tsiropoulos I, Kristensen O, Klitgaard NA. Saliva and serum concentration of lamotrigine in patients with epilepsy. Ther Drug Monit 2000 Oct; 22: 517–21

    Article  PubMed  CAS  Google Scholar 

  46. Meyer FP, Banditt P, Schubert A, et al. Lamotrigine concentrations in human serum, brain tissue, and tumor tissue. Epilepsia 1999 Jan; 40: 68–73

    Article  PubMed  CAS  Google Scholar 

  47. Cohen AF, Land GS, Breimer DD, et al. Lamotrigine, a new anticonvulsant: pharmacokinetics in normal humans. Clin Pharmacol Ther 1987; 42: 535–41

    Article  PubMed  CAS  Google Scholar 

  48. Yuen WC, Peck AW. Lamotrigine pharmacokinetics: oral and i.v. infusion in man. Proceedings of the British Pharmacological Society; 1988 Apr 6–8. Br J Clin Pharmacol 1988; 26(2): 242P

    Google Scholar 

  49. Ramsay RE, Pellock JM, Garnett WR, et al. Pharmacokinetics and safety of lamotrigine (Lamictal) in patients with epilepsy. Epilep Res 1991; 10: 191–200

    Article  CAS  Google Scholar 

  50. Jawad S, Yuen WC, Peck AW, et al. Lamotrigine: single-dose pharmacokinetics and initial 1 week experience in refractory epilepsy. Epilepsy Res 1987; 1: 194–201

    Article  PubMed  CAS  Google Scholar 

  51. Rambeck B, Wolf P. Lamotrigine clinical pharmacokinetics. Clin Pharmacokinet 1993; 25(6): 433–43

    Article  PubMed  CAS  Google Scholar 

  52. Garnett WR. Lamotrigine: pharmacokinetics. J Child Neurol 1997 Nov; 12 Suppl. 1: S10–5

    Article  PubMed  Google Scholar 

  53. Mikati MA, Schachter SC, Schomer DL, et al. Long-term tolerability, pharmacokinetic and preliminary efficacy study of lamotrigine in patients with resistant partial seizures. Clin Neuropharmacol 1989; 12(4): 312–21

    Article  PubMed  CAS  Google Scholar 

  54. Berry DJ. The disposition of lamotrigine throughout pregnancy [abstract no. 90]. Ther Drug Monit 1999 Aug; 21: 450

    Article  Google Scholar 

  55. Ohman I, Vitols S, Tomson T. Lamotrigine in pregnancy: pharmacokinetics during delivery, in the neonate, and during lactation. Epilepsia 2000 Jun; 41: 709–3

    Article  PubMed  CAS  Google Scholar 

  56. Peck AW. Clinical pharmacology of lamotrigine. Epilepsia 1991; 32 Suppl. 2: S9–S12

    Article  PubMed  Google Scholar 

  57. Elwes RDC, Binnie CD. Clinical pharmacokinetics of newer antiepileptic drugs: lamotrigine, vigabatrin, gabapentin and oxcarbazepine. Clin Pharmacokinet 1996 Jun; 30: 403–15

    Article  PubMed  CAS  Google Scholar 

  58. Posner J, Holdich T, Crome P. Comparison of lamotrigine pharmacokinetics in young and elderly healthy volunteers. J Pharm Med 1991; 1: 121–8

    Google Scholar 

  59. Sathanandar ST, Blesi K, Tran TA, et al. Lamotrigine clearance increases markedly during pregnancy [abstract no. J.02]. Epilepsia 2000; 41 Suppl. 7: 246

    Google Scholar 

  60. Wootton R, Soul-Lawton J, Rolan PE, et al. Comparison of the pharmacokinetics of lamotrigine in patients with chronic renal failure and healthy volunteers. Br J Clin Pharmacol 1997 Jan; 43: 23–7

    Article  PubMed  CAS  Google Scholar 

  61. Fillastre JP, Taburet AM, Fialaire A, et al. Pharmacokinetics of lamotrigine in patients with renal impairment: influence of haemodialysis. Drugs Exptl. Clin. Res 1993; 19(1): 25–32

    CAS  Google Scholar 

  62. Chen C, Veronese L, Yin Y. The effects of lamotrigine on the pharmacokinetics of lithium. Br J Clin Pharmacol 2000 Sep; 50(3): 193–5

    Article  PubMed  CAS  Google Scholar 

  63. Odishaw J, Chen C. Effects of steady-state bupropion on the pharmacokinetics of lamotrigine in healthy subjects. Pharma-cotherapy 2000 Dec; 20(12): 1448–53

    CAS  Google Scholar 

  64. Mustafa AA, Al-Humayyd MS. The effect of parenteral imipramine on the oral absorption of lamotrigine in rats. Int J Pharm 1997 Jun 26; 152: 207–13

    Article  CAS  Google Scholar 

  65. Anderson GD, Yau MK, Gidal BE, et al. Bidirectional interaction of valproate and lamotrigine in healthy subjects. Clin Pharmacol Ther 1996 Aug; 60: 145–56

    Article  PubMed  CAS  Google Scholar 

  66. Böttiger Y, Ståhle L. Lamotrigine drug interactions in a TDM material [abstract no. 84]. Ther Drug Monit 1997 Oct; 19: 568

    Article  Google Scholar 

  67. Edelbroek PM, Segers JP, Gilissen KGPM, et al. Population pharmacokinetics of lamotrigine to evaluate interaction with concommitant antiepileptic drugs. Epilepsia 1996; 37 Suppl. 4: 64

    Google Scholar 

  68. Hossain M, Chen C, Ette E. Characterization of lamotrigine (LTG) drug interactions using the population approach [abstract no. 3148]. Pharm Res 1997 Nov; 14 (11 Suppl.): S515

    Article  Google Scholar 

  69. May TW, Rambeck B. Influence of oxcarbazepine and methsux-imide on LTG concentrations [abstract]. Epilepsia 1998; 39 Suppl. 2: 25

    Google Scholar 

  70. Rambeck B, Specht U, Wolf P. Pharmacokinetic interactions of the new antiepileptic drugs. Clin Pharmacokinet 1996 Oct; 31: 309–24

    Article  PubMed  CAS  Google Scholar 

  71. Maly MM, Gidal BE, Rutecki P, et al. Effect of lamotrigine on carbamazepine epoxide/carbamazepine seram-concentration ratios [abstract no. 3.049]. Epilepsia 1997; 38 Suppl. 8: 101

    Google Scholar 

  72. 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 Nov; 61(11): 841–50

    Article  PubMed  CAS  Google Scholar 

  73. 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 1999 Feb; 60(2): 79–88

    Article  PubMed  CAS  Google Scholar 

  74. 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 Dec; 20(6): 607–14

    Article  PubMed  CAS  Google Scholar 

  75. Data on file, GlaxoSmithKline. 2003

  76. American Pyschiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Pyschiatric Association, 1994

    Google Scholar 

  77. Calabrese JR, Bowden CL, Fieve R, et al. Lamotrigine or lithium in the maintenance treatment of bipolar I disorder [abstract no. P.1.115 plus poster]. Presented at the 15th Congress of the European College of Neuropsychopharmacology; 2002 Oct 5–9; Barcelona. Eur Neuropsychopharmacol 2002; 12 Suppl. 3: S217

    Article  Google Scholar 

  78. Bowden CL, Asnis GM, Ginsburg LD, et al. Safety and tolerability of lamotrigine for bipolar disorder; GlaxoSmithKine..

  79. 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 Nov; 63(11): 1012–9

    Article  PubMed  Google Scholar 

  80. Obrocea GV, Dunn RM, Frye MA, et al. Clinical predictors of response to lamotrigine and gabapentin monotherapy in refractory affective disorders. Biol Psychiatry 2002 Feb 1; 51(3): 253–60

    Article  PubMed  CAS  Google Scholar 

  81. Burgess S, Geddes J, Hawton K, et al. Lithium for maintenance treatment of mood disorders (Cochrane Review). In: The Cochrane Library, Issue2. Oxford: Update software [online]. Available from URL: http://www.cochranelibrary.com [Accessed 2003 Jul 10]

  82. Strakowski SM, DelBello MP, Adler CM. Comparative efficacy and tolerability of drug treatments for bipolar disorder. CNS Drugs 2001; 15(9): 701–18

    Article  PubMed  CAS  Google Scholar 

  83. Calabrese JR, Bowden CL, McElroy SL, et al. Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder. Am J Psychiatry 1999 Jul; 156(7): 1019–23

    PubMed  CAS  Google Scholar 

  84. Bryant-Comstock L, Mather DB, Lee TA, et al. Treatment of bipolar depression: clinical and economic outcomes [abstract no. NR516]. American Psychiatric Association Annual Meeting; 2000 May 13–18; Chicago. The doctor-patient relationship: new research abstracts. Chicago (IL): American Psychiatric Association, 197–218

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  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 1311, New Zealand

    David R. Goldsmith, Antona J. Wagstaff, Tim Ibbotson & Caroline M. Perry

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Additional information

Various sections of the manuscript reviewed by: M. Berk, Department of Psychiatry, University of Melbourne, Geelong, Victoria, Australia; C.L. Bowden, Department of Psychiatry, University of Texas Health Science Center, San Antonio, Texas, USA; J.R. Calabrese, Mood Disorders Program, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; R.T. Joffe, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA; T.A. Ketter, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA; P.B. Mitchell, School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.

Data Selection

Sources: Medical literature published in any language since 1980 on lamotrigine, identified using Medline and EMBASE, supplemented by AdisBase (a proprietary database of Adis International). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: Medline search terms were ‘lamotrigine’ and (‘bipolar*’ or ‘manic depression’ or ‘mania’ or ‘depressive’ or ‘depression’ or ‘affective’ or ‘manic depressive disorder’). EMBASE search terms were ‘lamotrigine’ and (‘bipolar’ or ‘depression’ or ‘manic depression’ or ‘mania’ or ‘manic depressive disorder’ or ‘affective’). AdisBase search terms were ‘lamotrigine’ and (‘manic depression’ or ‘mania’ or ‘bipolar depression’ or ‘bipolar-disorders’ or ‘depression’ or ‘depressive’ or ‘antidepress*’ or ‘affective’). Searches were last updated 6th August 2003.

Selection: Studies in patients with bipolar disorder who received lamotrigine. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: lamotrigine, bipolar disorder, depression, mania, pharmacodynamics, pharmacokinetics, therapeutic use.

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Goldsmith, D.R., Wagstaff, A.J., Ibbotson, T. et al. Lamotrigine. Drugs 63, 2029–2050 (2003). https://doi.org/10.2165/00003495-200363190-00009

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