Disease relevance of lamotrigine

• Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome [1].
• Lamotrigine for generalised epilepsies [2].
• Lamotrigine and toxic epidermal necrolysis [3].
• Lamotrigine in infantile spasms [4].
• Hyponatraemia associated with lamotrigine in cranial diabetes insipidus [5].
• To our knowledge, in addition to being the first case report to describe convulsive status epilepticus after lamotrigine intoxication, this is the first report of the proconvulsant effect of lamotrigine in a case of localization-related epilepsy in an adult [6].

Psychiatry related information on lamotrigine

• The results indicate that lamotrigine is an effective, well-tolerated maintenance treatment for bipolar disorder, particularly for prophylaxis of depression [7].
• Aggression in dementia with lamotrigine treatment [8].
• Hallucinations during lamotrigine treatment of bipolar disorder [9].
• A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder [10].
• LTG increased REM sleep, reduced number of entries into REM sleep, decreased number of phase shifts, and decreased percentage of slow-wave sleep [11].

High impact information on lamotrigine

• Using dendritic and somatic whole-cell and cell-attached recordings in rat hippocampal slices, we found that the anticonvulsant lamotrigine selectively reduced action potential firing from dendritic depolarization, while minimally affecting firing at the soma [12].
• It is possible that the effect of lamotrigine on fluid balance in the cases described is also centrally mediated [5].
• We report the cases of two children with cranial diabetes insipidus who were treated with lamotrigine for seizures and who had accompanying changes in desmopressin requirements [5].
• For individual antiepileptic drugs the univariate relative risk of SJS/TEN for 8 weeks or less of use was 57 (95% CI 16-360; multivariate risk 59 [12-302]) for phenobarbital; 91 (26-infinity) for phenytoin; 120 (34-infinity) for carbamazepine; 25 (5.6-infinity) for lamotrigine, and 24 (5.9-infinity) for valproic acid [13].
• Loss of aura in lamotrigine-treated epilepsy [14].

Chemical compound and disease context of lamotrigine

• METHOD: A post hoc analysis was conducted to assess the effects of lamotrigine, lithium, and placebo administration on body weight in obese and nonobese patients with bipolar disorder from two double-blind, placebo-controlled, 18-month studies [15].
• Treatment-resistant bipolar depression: a STEP-BD equipoise randomized effectiveness trial of antidepressant augmentation with lamotrigine, inositol, or risperidone [16].
• Two children developed multiorgan dysfunction with disseminated intravascular coagulation 9 days after lamotrigine was added to their antiepileptic therapy, which included valproic acid [17].
• A comparison was made between the incidence of hyperandrogenism (hirsutism, acne, male-pattern alopecia, elevated androgens) with oligoamenorrhea that developed while taking valproate versus other anticonvulsants (lamotrigine, topiramate, gabapentin, carbamazepine, oxcarbazepine) and lithium [18].
• Anticonvulsant compounds of the lamotrigine type, which act on sodium channels and reduce ischemia-induced glutamate release, are cerebroprotective in rodent ischemia models and are free from the cognitive side effects of NMDA-receptor antagonists [19].

Biological context of lamotrigine

• The pharmacokinetics of lamotrigine, a new anticonvulsant, were studied in three studies in normal volunteers [20].
• In a second study 10 subjects received 120 mg lamotrigine and the mean (+/- SD) of the elimination half-life (t1/2) was 24.1 +/- 5.7 hours and of volume of distribution/bioavailability 1.2 +/- 0.12 L/kg [20].
• After dose adjustment of lamotrigine to 200 mg twice daily, the AUC on day 31 (n = 15) was bioequivalent to that on day 10, with a point estimate of 0.91 (90% confidence interval, 0.82-1.02) [21].
• Carbamazepine, oxcarbazepine, and lamotrigine also inhibited electrically stimulated release of [3H]-5-hydroxytryptamine (IC50 values, 150 to 250 microM) and [3H]-acetylcholine (IC50 values, 50 to 150 microM); [3H]-noradrenaline release was affected to a lesser degree [22].
• Lamotrigine at 50 mg/kg i.v. for 10 minutes was not cerebroprotective and induced a decrease of 29 +/- 15 mm Hg in mean arterial blood pressure (P < .05, n = 8) [23].

Anatomical context of lamotrigine

• In addition, the selective induction of glucuronidation activity toward lamotrigine, ethinyl estradiol, chenodeoxycholic acid, and lithocholic acid by either PCN or TCDD in small intestine from Tg-UGT1 mice corresponded to expression of the locus in this tissue [24].
• Lamotrigine completely protected gerbils exposed to 15 minutes of cerebral ischemia against CA3 cell loss and greatly reduced damage to the CA1 and CA2 cell tracts of the hippocampus [25].
• Lymphocytes from 3 of 4 lamotrigine-hypersensitive patients proliferated when stimulated with lamotrigine [26].
• To help characterize their site and mode of action on sodium channels, a member of the lamotrigine family, R-(-)-2,4-diamino-6-(fluromethyl)-5-(2,3,5-trichlorophenyl)-pyrimidine (BW202W92), was radiolabeled and used as a binding ligand in rat forebrain synaptosomes [27].
• The T-cell receptor of certain clones could accommodate analogs of lamotrigine, but no cross-reactivity was seen with other anticonvulsants [26].

Associations of lamotrigine with other chemical compounds

• Felbamate, gabapentin, lamotrigine and vigabatrin are among the most promising of this new generation of drugs and, when used as add-on therapy, provide some improvement in a significant number of patients suffering from previously refractory epilepsy whilst exhibiting a lower risk of unwanted side-effects than traditional antiepileptic drugs [28].
• We studied premenopausal women with epilepsy receiving antiepileptic drug monotherapy (phenytoin, carbamazepine, valproate, and lamotrigine) [29].
• We have reviewed the pharmacokinetics of six antiepileptic drugs that are marketed (felbamate, gabapentin, lamotrigine, oxcarbazepine, vigabatrin, and zonisamide) and six drugs that are undergoing evaluation (levetiracetam, ralitoline, remacemide, stiripentol, tiagabine, and topiramate) [30].
• We studied the effect of lopinavir/ritonavir on the pharmacokinetics of lamotrigine and vice versa [21].
• CONCLUSION: Lopinavir/ritonavir decreases the AUC of lamotrigine, probably by induction of glucuronidation [21].

Gene context of lamotrigine

• The PPI deficit of the mGluR1 KO mice was, however, ameliorated by administration of the mood stabilizer lamotrigine (27 mg/kg base equivalent weight), though increases in PPI were also seen with lamotrigine in the wild-type mice [31].
• Lamotrigine significantly prevented loss of hippocampal CA1 neurons when administered acutely (100 mg/kg PO) immediately after reperfusion or when administered in two equal doses of 30 or 50 mg/kg 2 hours before and immediately after reperfusion [25].
• Unlike lithium or valproic acid, however, lamotrigine does not down-regulate the expression of protein kinase C or MARCKS, suggesting that lamotrigine employs different intracellular mechanisms for long-term changes in neuro-biology from those of lithium or valproic acid [32].
• When comparing AED concentrations in the ECS with those in the CSF, ECS concentrations were significantly lower for CBZ, 10-OH-CZ, LTG, and LEV [33].
• Lamotrigine inhibits basal and Na(+)-stimulated, but not Ca (2+)-stimulated, release of corticotropin-releasing hormone from the rat hypothalamus [34].

Analytical, diagnostic and therapeutic context of lamotrigine

• BACKGROUND: Lamotrigine has been shown to be an effective treatment for bipolar depression and rapid cycling in placebo-controlled clinical trials [7].
• This study was designed to provide preliminary evidence for the safety and efficacy of a new anticonvulsant, lamotrigine, in adult patients with bipolar disorder who had been inadequately responsive to or intolerant of prior pharmacotherapy [35].
• METHODS: The cognitive and behavioral effects of carbamazepine and lamotrigine were assessed in 25 healthy adults using a double-blind, randomized crossover design with two 10-week treatment periods [36].
• Daily NPS in the lamotrigine-treated group was reduced from 6.4 +/- 0.1 to 4.2 +/- 0.1 and in the control group from 6.5 +/- 0.1 to 5.3 +/- 0.1 (p < 0.001 for lamotrigine doses of 200, 300, and 400 mg) [37].
• A small double-blind study demonstrates efficacy when lamotrigine is added to clozapine [38].

References