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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. Lamotrigine is a new anticonvulsant chemically unrelated to other existing antiepileptic drugs. Studies suggest it acts at voltage-sensitive sodium channels and also decreases calcium conductance. Both of these mechanisms of action are shared by carbamazepine, which can cause hyponatraemia secondary to inappropriate secretion of antidiuretic hormone. It is possible that the effect of lamotrigine on fluid balance in the cases described is also centrally mediated.
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PMID:Hyponatraemia associated with lamotrigine in cranial diabetes insipidus. 1096 44

The effectiveness of lamotrigine as a monotherapeutic agent for a variety of pediatric epilepsies was reviewed retrospectively. Children were categorized as having focal vs generalized epilepsy and according to whether they were antiepileptic drug naive or drug exposed. Data collected included dosages, side effects, length of follow-up, number of prior drugs, and treatment response. Treatment was considered successful if the patient was seizure free for 6 months or more. Eighty-three children were identified (average age = 8.7 years); 43 had focal epilepsy, 32 had generalized epilepsy, and eight were not classified. Twenty-nine patients were classified as having specific syndromes. Fourteen patients were drug naive. The median follow-up period was 8 months (mean = 8.5). Overall, 45% were seizure free, 44% with focal epilepsy and 36% with generalized epilepsy. All children with juvenile myoclonic epilepsy and benign rolandic epilepsy of childhood were seizure free, although not all had been treated for at least 6 months. One third of drug-naive patients were seizure free. Rash was the most common side effect and was reported in five patients (6%); two patients discontinued the drug. None had Stevens-Johnson syndrome. One quarter of children experienced nonquantifiable improvements, namely increased alertness and improved behavior regardless of seizure control. Lamotrigine is effective as a monotherapeutic agent in children for both focal and generalized epilepsies. Side effects are relatively uncommon. Lamotrigine may be an effective firstline agent.
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PMID:Lamotrigine monotherapy in children. 1102 Jun 42

Lamotrigine is a broad-spectrum antiepileptic drug that blocks sodium channels, thereby inhibiting the pre-synaptic release of excitatory neurotransmitters. The primary aim of the study was to evaluate lamotrigine add-on therapy and consecutive monotherapy in patients with epilepsy whose seizures were not controlled by carbamazepine or valproate. One hundred and twenty six epilepsy patients at 18 centres in Poland were recruited into a lamotrigine substitution study. In all patients, existing seizures were poorly controlled with valproate (n= 63) or carbamazepine (n= 63) monotherapy. The study consisted of four phases: (1) a 4-week lamotrigine dose-escalation phase, (2) an 8-week lamotrigine add-on phase, (3) an 8-week carbamazepine/valproate withdrawal phase, and (4) an 8-week lamotrigine monotherapy phase. Of 126 patients recruited into the study, 107 (85%) completed dose-escalation and add-on therapy with lamotrigine and 85 (68%) completed lamotrigine monotherapy. Fifty percent of patients during add-on therapy and 53% during lamotrigine monotherapy experienced at least 50% reduction in total seizures (responders) compared to the pre-study period. Approximately 20% of patients during add-on therapy and 27% during lamotrigine monotherapy were seizure free. Total well-being was assessed using a Visual Analogue Scale with 62% of patients during add-on therapy and 60% in lamotrigine monotherapy reporting improvement in scores. Lamotrigine was generally well tolerated. Treatment was discontinued in 7% because of adverse events. In conclusion, lamotrigine is an effective AED in add-on therapy and monotherapy, it is safe and well tolerated, and successful conversion from add-on to monotherapy can be achieved in many cases. An additive effect between lamotrigine and valproate was observed.
Seizure 2000 Oct
PMID:Open study evaluating lamotrigine efficacy and safety in add-on treatment and consecutive monotherapy in patients with carbamazepine- or valproate-resistant epilepsy. 1103 73

Lamotrigine (LTG) is a novel antiepileptic drug effective in partial and generalized seizures. Recently, this drug has started being used for mood stabilization in psychiatric patients. Cutaneous side effects of this drug are mostly maculopapular eruptions that have been seen in 3% to 10% of patients. We describe a 33-year-old female patient in whom Stevens-Johnson syndrome (SJS) developed because of LTG. The drug was discontinued, and patient's signs and symptoms progressively resolved in 10 days after oral prednisolone therapy. The case is relevant because this is the first case of SJS as a result of LTG, probably associated with concomitant use of valproic acid and neuroleptic drugs.
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PMID:Stevens-Johnson syndrome associated with concomitant use of lamotrigine and valproic acid. 1104 15

We evaluated the efficacy and safety of lamotrigine in 41 children and young adults (age range, 3-25 years; mean, 12 years) with drug-resistant, partial epilepsies, based on a prospective, add-on study. Patients had severe symptomatic/cryptogenic partial epilepsies (mean seizure frequency = 3.6/day), resistant to one to four major antiepileptic drugs. Mean seizure frequency significantly decreased (P < .001) throughout the period of treatment. A good response (>50% seizure reduction) was observed in 15 patients of whom 6 were seizure-free (follow-up: 12-48 months). Higher responder rate was found among cryptogenic epilepsies and epilepsies symptomatic of cerebral malformation, whereas patients with posthypoxic-ischemic perinatal damage were poor responders. Lamotrigine discontinuation was mainly due to lack of efficacy (46% of patients), whereas only 2 patients developed a transient skin rash and did not drop out. Lamotrigine represents a valuable treatment for severe partial epilepsies of childhood that have proved resistant to previous antiepileptic drugs.
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PMID:Add-on lamotrigine treatment in children and young adults with severe partial epilepsy: an open, prospective, long-term study. 1106 81

For pure childhood absence epilepsy (CAE), ethosuximide (ESM) remains the drug of first choice. Although valproic acid (VPA) is of equal efficacy, it is more toxic, and is reserved for those patients with accompanying convulsions. Lamotrigine (LTG) is effective as both add-on and monotherapy for CAE. If any of these three drugs fails, one of the other two can be used as monotherapy. Rarely, when ESM, VPA, or LTG does not effectively control CAE, phenytoin (PHT), primidone (PRM), and phenobarbital (PB) may be partially effective, although carbamazepine (CBZ) may worsen absence seizures. Experience is limited with the newer AEDs. Tiagabine (TGB) may induce absence status epilepticus in PGE. Oxcarbazepine (OXC) and vigabatrin (VGB) may worsen absence seizures. Felbamate (FBM) is probably effective, but is potentially fatal. Lifelong therapy is not anticipated. For juvenile absence epilepsy (JAE), VPA is the drug of first choice. LTG is also of proven efficacy. The risks of VPA-induced teratogenicity (possibly lessened by the concurrent use of folic acid) and weight gain are potentially unacceptable in young women of childbearing age. Not enough data exists on the safety of LTG in pregnancy. A combination of VPA and LTG can be used if either drug alone is unsuccessful. For juvenile myoclonic epilepsy (JME), VPA is the traditional drug of first choice in most patients. As in JAE, side effects may make VPA an unacceptable choice in many patients, especially young women. In clinical practice, TPM is being increasingly used as monotherapy for JME. Many patients appreciate the accompanying weight loss seen with TPM, but it has potentially troubling side effects, has not been well studied as monotherapy for JME, and its safety in pregnancy has yet to be confirmed. PHT and CBZ may worsen myoclonus when used alone, but they may have a role as add-on treatment to VPA, LTG, or TPM, especially when generalized tonic-clonic seizures (GTCSs) are not controlled. PB and PRM may also be useful as add-on treatment, but often have unacceptable side effects. Clonazepam may be useful as adjunctive treatment for resistant myoclonic jerks. OXC and VGB both worsen myoclonic seizures. GBP is not useful in JME and can make seizures worse. The efficacy of FBM and TGB in JME is largely unknown. Lifelong AED therapy is necessary. In epilepsy with generalized tonic-clonic seizure (GTCS) on awakening (EGA), VPA is the drug of choice, especially if other seizure types (absence and myoclonic) are present. If only GTCSs are present, then PB, PHT, and CBZ may be as effective as VPA; however, the use of PHT and CBZ may "unearth" other seizure types (absence and myoclonic) in those patients with EGA, although PB is poorly tolerated. As for JME, LTG, and TPM may both be effective monotherapy for EGA, although the use of other AEDs in EGA has not been well studied. Lifelong AED treatment is necessary.
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PMID:Primary Generalized Epilepsies. 1109 77

Lamotrigine (LTG) is one of the newer antiepileptic drugs which has been shown to have a spectrum of drug interactions (including with other epilepsy drugs) that can have a pronounced effect on LTG kinetics. The present study examined the LTG metabolic inhibition dose-response relationship with valproic acid (VPA) in eight patients with epilepsy with a view to using this to benefit the patient. This could benefit the patient not only by attaining higher plasma LTG concentrations with "standard" dosages of LTG, but also possibly by achieving better seizure control through providing a less variable peak-to-trough fluctuation in LTG concentrations as a result of extending the half-life of LTG. The dosages of VPA trialed were 0, 200, 500, and 1,000 mg/d which resulted in a mean increase in LTG area under the curve of 83.7 +/- 14.7% at 200 mg VPA/d, to and 160 +/- 37.9% at 1,000 mg VPA/d. The presence of concomitant enzyme inducers in some patients did not influence the percentage increase from baseline in half-life observed, although clearly those on inducers started from a lower absolute half-life as a result of the induction. The effect was shown to be quite variable, particularly at the highest dosage of VPA tested (1,000 mg/d), suggesting that this effect could be best applied with the support of the therapeutic drug monitoring laboratory determining plasma LTG concentrations to allow individualization of the LTG dosage.
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PMID:Clinical study of lamotrigine and valproic acid in patients with epilepsy: using a drug interaction to advantage? 1112 32

Epilepsy is common in the elderly. The incidence of epilepsy is age-dependent, with a peak during the first year of life and higher incidence in those older than 75 years. Cerebrovascular disease is a common cause of epilepsy in the elderly. Drug treatment of the elderly is a challenge because of pharmacokinetic changes with aging, including impaired drug protein binding or displacement of drug from protein binding sites, potentially causing drug toxicity as a result of increased free drug concentrations. With aging, hepatic mass and blood flow decline along with renal function. Established anticonvulsant drugs have adverse effects and drug interactions that can make treating the elderly difficult. Newly available anticonvulsants cause fewer drug-drug interactions and less toxicity. Gabapentin is not metabolised, is not bound to protein, and has a favourable adverse effect profile and thus may be useful in the treatment of elderly patients. Lamotrigine reduced seizures between 20 and 30% in trials. Dose response was between 300mg per day and 500mg per day. This drug was well tolerated in open-label trials. Rash occurred in younger patients. Oxcarbazepine is rapidly absorbed and is converted to a monohydroxy derivative. Use with hepatic enzyme-inducing drugs necessitates an increase in dose. This drug may be substituted for carbamazepine. Hyponatraemia has been reported and monitoring is suggested. Topiramate blocks voltage-dependent sustained repetitive firing and has an effect on the gamma-aminobutyric acid (GABA) receptors. It affects glutamate responses and inhibits carbonic anhydrase. Topiramate has a dose response pattern up to 400mg per day. Cognitive effects limits its use in some patients. Nephrolithiasis has occurred with this drug. Tiagabine blocks GABA transporter proteins. Clearance is rapid and metabolism complete. Hepatic dysfunction prolongs clearance. The use of tiagabine has not been reported in the elderly. Zonisamide is rapidly absorbed and protein binding is 50%. Plasma half-life is 55 hours but is reduced to about 30 hours by hepatic enzyme-inducing drugs. Responder rate is 45%. Adverse effects include drowsiness, altered thinking and nephrolithiasis. Treatment of the elderly requires obligatory polypharmacy with potential drug interactions. Changes in body physiology alter absorption, binding, metabolism and elimination of drugs. Concomitant illness and sensitivity to drug effects narrow the therapeutic range and complicate pharmacokinetics in elderly patients. Newer anticonvulsant drugs have advantages that may outweigh risks and have therapeutic profiles that may aid in the treatment of this special population of patients.
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PMID:Choice and use of newer anticonvulsant drugs in older patients. 1120 Mar 5

Rett syndrome (RS) is a particular neurodevelopmental disorder in which symptoms develop in early infancy and manifests particular symptoms at certain ages. Two girls aged 4.5 and 2.5-years-old were admitted with complaints of seizures, regression of language, psychomotor development, and autistic behavior. They had fulfilled the criteria of classic RS. Lamotrigine was used in the treatment of the convulsions. After lamotrigine therapy, the convulsions were successfully controlled and the stereotyped hand movements and autistic behaviors markedly decreased. We would like to stress that, aside from convulsion, abnormal signs of the syndrome such as stereotyped hand movements and autistic behaviors might also be improved with lamotrigine, but detailed and controlled studies should be performed to identify whether lamotrigine has any positive effects in RS.
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PMID:Lamotrigine in two cases of Rett syndrome. 1137 3

This review touches on the historical links between epilepsy, seizures and the uterus and ovaries which have fascinated and misled physicians since Greco-Roman times. It then examines present knowledge of ovarian function and its effect on epileptic activity and vice versa before exploring the modern controversy about polycystic ovaries and the polycystic ovary syndrome, epilepsy and anticonvulsant medication. Based on present evidence, women with epilepsy are more prone to develop polycystic (polyfollicular) ovaries than other women due to the epilepsy itself. But women with epilepsy related polycystic (polyfollicular) ovaries are vulnerable to the effects of sodium valproate (possibly particularly during adolescence) and may develop the polycystic ovary syndrome: this is reversible if the valproate is withdrawn. Lamotrigine and carbamazepine seem to prevent the development of the syndrome.
Seizure 2001 Apr
PMID:Epilepsy and the ovary (cutting out the hysteria). 1143 23


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