Efficacy and tolerability of conversion to monotherapy with lamotrigine compared with valproate and carbamazepine in patients with epilepsy

OBJECTIVE: This randomized, open-label study was designed to compare the efficacy and tolerability of lamotrigine monotherapy with those of valproate and carbamazepine monotherapy in patients with epilepsy whose seizures were uncontrolled on their prestudy antiepileptic drug monotherapy. METHODS: Patients meeting eligibility criteria were randomized 2:1 to lamotrigine:carbamazepine or lamotrigine:valproate. The treatment phase was divided into a 4-week dose-escalation phase (Weeks 1-4), during which lamotrigine, carbamazepine, or valproate was added to patient's prestudy monotherapy; an 8-week add-on phase (Weeks 5-12), during which patients were stabilized on both the study medication and their prestudy antiepileptic therapy; an 8-week withdrawal phase (Weeks 13-20), during which prestudy antiepileptic therapy could be withdrawn if clinically appropriate; and an 8-week monotherapy phase (Weeks 21-28), during which patients could be treated with study medication as monotherapy. RESULTS: The numbers of patients randomized to the carbamazepine and valproate arms of the study were 144 (98 lamotrigine, 46 carbamazepine) and 158 (105 lamotrigine, 53 valproate), respectively. Successful monotherapy sustained for at least 7 weeks was achieved in comparable percentages of patients in the lamotrigine group (56%) and the carbamazepine group (54%) and in more patients in the lamotrigine group (49%) than the valproate group (40%). Among monotherapy completers, the percentage of patients with zero seizures during the monotherapy phase was comparable for lamotrigine (41%) and carbamazepine (30%) and significantly higher (P<0.05) with lamotrigine (32%) than with valproate (11%). No differences between treatments were observed with respect to time to treatment failure or time to first seizure. Lamotrigine was also better tolerated than carbamazepine or valproate. CONCLUSION: Lamotrigine monotherapy was as effective as and better tolerated than carbamazepine or valproate monotherapy in patients whose seizures were uncontrolled on their prestudy antiepileptic drug monotherapy.     

Open study evaluating lamotrigine efficacy and safety in add-on treatment and consecutive monotherapy in patients with carbamazepine- or valproate-resistant epilepsy.

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.     

Effectiveness of lamotrigine in clinical practice: results of a retrospective population-based study

OBJECTIVE: Evaluation of the effectiveness of lamotrigine in a population-based cohort of epilepsy patients. METHODS: Medical charts of 360 patients treated in 37 centres in The Netherlands were reviewed. Effectiveness of lamotrigine therapy was assessed during the first year of use, with patients serving as their own controls. Effectiveness was measured by reduction in seizure frequency and retention time. RESULTS: Effectiveness could only be assessed in 165 patients; assessment in remaining patients was not possible due to various reasons, such as insufficient medical chart information. Lamotrigine was effective in 40% of patients who had been prescribed lamotrigine because of insufficient seizure control (n=112), and 14% of these 112 patients became seizure free. Duration of epilepsy, baseline seizure frequency, valproate use, drug load and number of antiepileptic drugs (AED) used were related to effectiveness of lamotrigine. In this group, 36% continued lamotrigine (LTG) throughout the first year without experiencing a >50% seizure reduction. Lamotrigine was effective in 63% of patients who received the drug because of poor tolerability of other antiepileptic drugs (n=53). DISCUSSION: Lamotrigine is an effective drug in clinical practice. Use of retention time measures only may not correctly reflect the efficacy of antiepileptic drugs.     

Reinvestigation and reduction of polytherapy in children with chronic seizures

From October 2001 to October 2003, the authors reviewed all patients with chronic seizures taking antiepileptic drugs for more than 2 years with follow-up at the pediatric neurological clinic. They identified 31 patients who were using 3 or more drugs. Twenty-nine patients agreed to undergo a drug reduction and readjustment. The authors spent a mean period of 14.1 months to either purely reduce the numbers of drugs or introduce a new drug (rational polytherapy) plus removal of some drugs to achieve the end goal of a maximum of 2 or 3 drugs (if necessary). Seizure control in 96.6% of patients (28 of 29 patients) did not worsen after the readjustment and reduction of the antiepileptic drugs. Instead, 65.5% (19 of 29 patients) got better, and 37.9% (11 of 29) were seizure free. The number of antiepileptic drugs before and after adjusting was 3.6 (range, 3-6) to 1.9 (4 monotherapy, 22 duotheray, and 2 triple drugs). The most common combined therapies were sodium valproate/lamotrigine (n = 10) and carbamazepine/ topiramate (n = 5). Although the results could be possibly attributed to the spontaneous remission of the seizures, it was still shown that those patients were overtreated. Serial addition to 3 or more antiepileptic drugs is less likely to lead to seizure freedom for patients with difficult-to-treat epilepsy. On the contrary, polytherapy and some antiepileptic drugs could aggravate seizures. Certain combinations of antiepileptic drugs (rational polytherapy) offer better efficacy to control seizures.     

Open study evaluating lamotrigine efficacy and safety in add-on treatment and consecutive monotherapy in adult patients with epilepsy resistant carbamazepine and valproate

Lamotrigine is a broad-spectrum antiepileptic drug which is thought to act in part via a use-dependent blockade of voltage-sensitive sodium channels to stabilise the neuronal membrane. This results in the inhibition of the excessive release of excitatory amino acids, such as glutamate, during epileptic activity. An open, multicentre, prospective trial of lamotrigine was carried out in adult patients with drug-resistant epilepsy on monotherapy with carbamazepine or valproate. The primary aim of the study was to assess add-on lamotrigine withdrawing to monotherapy. 28-week clinical trial was divided into 4 phases: (1) Dose escalation period (4 weeks), (2) Add-on period (8 weeks), (3) Standard AED withdrawal period (8 weeks), (4) Lamotrigine monotherapy (8 weeks). Thirty-three patients were previously treated with valproate, 44 with carbamazepine. Of 77 patients recruited into the study, 64 patients (83%) completed add-on therapy, 49 patients (64%) completed lamotrigine monotherapy. 44% of all patients during the add-on phase and 48% during lamotrigine monotherapy had a reduction in seizure frequency of at least 50% compared with pre-study period. 13% of all patients achieved seizure freedom during add-on therapy and 18% during monotherapy. Improvement of Visual Analogue Scale (VAS) scores was observed in 65% and 57% patients respectively. A significant proportion of patients could be successfully converted to lamotrigine monotherapy. Lamotrigine was also generally well tolerated. 23 patients (30%) had at least one adverse event (AE), but only 1/4 of all AEs might be reasonably regarded as an effect of the medication. 7 patients (9%) discontinued prematurely from the study due to adverse event. More AEs were observed in add-on therapy than in lamotrigine monotherapy. The safety profile was consistent with that seen during other clinical trials with lamotrigine. CONCLUSIONS: 1. Lamotrigine is effective AED in add-on and monotherapy (responders rate--44% and 48% respectively). 2. In most cases conversion from add-on therapy to monotherapy can be done successfully. 3. Lamotrigine is a safe and well-tolerated drug.     

Use of antiepileptic drugs in the treatment of epilepsy in people with intellectual disability

The main principles of antiepileptic drug treatment of epilepsy in patients with intellectual disability are basically the same as for other patients with epilepsy. However, some specific issues need to be taken into account These are primarily associated with the diagnostic difficulties of epilepsy in this population. In addition, a number of other relevant issues, including the degree and location of brain lesion, the nature of the underlying disease, the higher frequency of difficult-to-treat epilepsies, the additional intellectual impairment caused by inappropriate antiepileptic medication, or by frequent and prolonged seizures, the appropriate use of monotherapy versus rational polytherapy, and the use of broad-spectrum antiepileptic drugs will be discussed in the present paper. Although the goals of treatment are to keep the patient seizure-free and alert while preventing possible mental deterioration, we have to accept compromises between these primary goals in many cases. Some people with epilepsy and intellectual disability are very vulnerable to insidious neurotoxic effects; for example, sedative effects caused by phenobarbital, or cognitive and/or cerebellar dysfunction caused by long-term phenytoin, especially together with other drugs. Because of the adverse effects of phenobarbital and phenytoin, these drugs are no longer recommended as a first-choice drugs when long-term antiepileptic medication is required. In primary generalized tonic-clonic seizures, valproate, oxcarbazepine/carbamazepine and lamotrigine are recommended in this order of preference. The corresponding recommendations are: in typical absences, valproate, ethosuximide and lamotrigine; in atypical absences, valproate and lamotrigine; in juvenile myoclonic epilepsy, valproate, lamotrigine and clobazam; in infantile spasms vigabatrin, ACTH and valproate; in Lennox-Gastaut syndrome, valproate, lamotrigine and vigabatrin; in atonic seizures, valproate and lamotrigine; in simple and complex partial seizures with or without secondary generalization, oxcarbazepine/carbamazepine, valproate/ vigabatrin and lamotrigine; and in status epilepticus lorazepam, diazepam and clonazepam together with phenytoin or fosphenytoin. In cases of poor response to the monotherapy recommended above, the following combinations may be indicated: in primary generalized tonic-clonic epilepsy, valproate and oxcarbazepine/ carbamazepine, or valproate and lamotrigine; in typical absences, valproate and lamotrigine, or valproate and ethosuximide; in juvenile myolonic epilepsy, valproate and lamotrigine, or valproate and clonazepam; and in partial epilepsies, add to the monotherapy one of the following drugs, vigabatrin, lamotrigine, gabapentin, tiagabine, topiramate, zonisamide or clobazam. So far, the order of preference of these new drugs remains undetermined. More data are needed on the efficacy and adverse effects of the new drugs based on controlled studies on patients with intellectual disability and epilepsy.     

Evolving antiepileptic drug treatment in juvenile myoclonic epilepsy

BACKGROUND: In the face of availability of newer antiepileptic drugs (AEDs) such as lamotrigine and topiramate, there is need to reassess the role of older AEDs in the treatment of juvenile myoclonic epilepsy (JME). OBJECTIVES: To explore whether lamotrigine and topiramate monotherapy or polytherapy can be effective options in the treatment of JME, and to determine whether older AEDs, such as phenytoin and carbamazepine, have a role in the treatment of JME. DESIGN: A retrospective cohort study. SETTING: A large academic teaching hospital. PATIENTS: Seventy-two consecutive JME patients treated with valproic acid, lamotrigine, topiramate, phenytoin, or carbamazepine between April 1, 1991, and March 31, 2001. METHODS: We compared the efficacy of valproic acid, lamotrigine, and topiramate monotherapy or polytherapy in the control of different seizure types of JME, and compared their efficacy and tolerability with the efficacy and tolerability of phenytoin and carbamazepine. RESULTS: Seizure outcome did not differ when patients receiving valproic acid monotherapy (n = 36) were compared with those receiving lamotrigine monotherapy (n = 14), and when patients receiving valproic acid polytherapy (n = 22) were compared with those receiving lamotrigine polytherapy (n = 21) or topiramate polytherapy (n = 15) (P>.05 for all). The combined data of myoclonic seizure control by all 3 AEDs were poorer when compared with the combined data of generalized tonic-clonic seizure control by all 3 AEDs (P =.03), but not when compared with the combined data of absence seizure control by all 3 AEDs (P =.43). Valproic acid, lamotrigine, and topiramate, when compared with phenytoin or carbamazepine, demonstrated significantly better control of myoclonic seizures (P<.01 for all), but not of generalized tonic-clonic seizures (P>.11 for all). CONCLUSIONS: Lamotrigine and topiramate are effective alternative options to valproic acid in the treatment of JME. Lamotrigine is an effective option as monotherapy and polytherapy. Topiramate is an effective option as polytherapy, but more data are needed to determine if it is an effective option as monotherapy. More effective therapy is needed to improve myoclonic seizure control. Older AEDs, such as phenytoin and carbamazepine, may not be indicated in JME patients.     

Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy

OBJECTIVE: This open-label study evaluated the efficacy and tolerability of lamotrigine monotherapy compared with monotherapy with conventional antiepileptic drugs in patients converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. METHODS: This study was conducted in 26 neurology clinics and epilepsy centers throughout the United States. The study enrolled 115 patients with epilepsy converting from previous monotherapy because of inadequate seizure control or unacceptable side effects. Patients were randomized 1:1 to receive 24 weeks of lamotrigine monotherapy or monotherapy with a conventional antiepileptic drug (carbamazepine, phenytoin, or valproate based on physician's choice). Patients were converted during an 相似文献   

Lamotrigine Serum Concentration in Children With Epilepsy

The correlation between lamotrigine serum concentration, efficacy, and toxicity in children is controversial. The database of the Clinical Pharmacology Laboratory at Assaf Harofeh Medical Center was retrospectively searched to identify lamotrigine serum concentrations in children aged 2-19 years with refractory epilepsy who received lamotrigine as monotherapy or polytherapy from 2007-2010. Data collected included age at epilepsy onset, additional antiepileptic drugs, lamotrigine dose, monthly seizure frequency before and after lamotrigine treatment, and side effects. Sixty blood samples were collected from 42 children aged 10.1 ± 4.9 years (range, 2-20 years). Seizure types included complex partial (n = 28), simple partial (n = 7), absence (n = 2), and generalized tonic-clonic (n = 23). Decreased seizure frequency was observed in 38 (63.3%) patients. No correlation with lamotrigine serum concentration was evident, but seizure frequency was significantly influenced by age and lamotrigine dose. Side effects were reported in 21 (35%) patients. Only diplopia was significantly correlated with lamotrigine serum concentration. Lamotrigine was more effective at lower doses and in older children. Lamotrigine serum concentration correlated significantly with diplopia, but not with other side effects or with clinical efficacy. Overall, lamotrigine is effective and safe in children with refractory epilepsy.     

Seizure freedom with different therapeutic regimens in intellectually disabled epileptic patients.

BACKGROUND: Epilepsy is a frequent condition in persons with intellectual disability and is more often difficult to treat than in the average population. Seizure freedom is the primary therapeutic goal which has important implications for the patient's quality of life. The aim of this study was to find out which antiepileptic therapy regimens (monotherapy or combination therapy) are effective in achieving this goal in intellectually disabled epilepsy patients. We were especially interested in the impact of the new antiepileptic drugs (AEDs) which were introduced during the past decade. METHOD: We investigated retrospectively the antiepileptic regimens on which the resident patients of a large epilepsy centre (as a rule with additional intellectual disabilities of different degrees) were seizure free in 2002. Information on antiepileptic medication and seizure frequency was taken out of the individual case documentation. It was also determined whether seizure free patients had already been seizure free in 1992. RESULTS: Two hundred and forty out of 675 patients (35,6%) with epilepsy were seizure free. The proportion of seizure freedom was 43,7% in patients with borderline intelligence, 39,2% in mild, 33,2% in moderate, 31,9% in severe, and 21,9% in profound intellectual disability. One hundred and twenty-two (50,8%) seizure free patients were on monotherapy; 53 of them were on CBZ (PB: 34, VPA: 25, PHT: 7, LTG: 3). Ninety-three patients (38,7%) were on duotherapies, CBZ/PB (27 patients), PB/PHT (17), and LTG/VPA (14) being the commonest. Of 18 (7,5%) triple therapies, LTG/PB/VPA (4 patients) was the commonest. Taken together, the five most frequent therapeutic regimens were CBZ monotherapy, PB monotherapy, CBZ/PB, VPA monotherapy and PB/PHT (a clear preponderance of classic AEDs). A distinction was made between "old seizure free" (seizure free already in 1992) and "new seizure free" (in 1992 still seizures) patients. In the 132 old seizure free patients the classic AEDs prevailed again, monotherapies with CBZ, PB and VPA being the most frequent regimens. In comparison, in the 78 new seizure free patients the novel combination LTG/VPA was the third most frequent, after the classic regimens CBZ/PB and CBZ; PB monotherapies were rare. CONCLUSION:In a majority of intellectually disabled patients with epilepsy (including those who became seizure free since 1992), complete seizure control has been achieved by monotherapy or duotherapy with classic AEDs. Of the new AEDs LTG in combination with VPA appears to be an important innovation.     

Lamotrigine: clinical experience in 93 patients with epilepsy

This open study reports the use of lamotrigine in 93 adults and children with drug resistant epilepsy. Lamotrigine was used predominantly as add-on therapy and outcome was assessed by the patient, parents and carers and the physician in terms of reduction of seizure frequency, drug side effects, and importantly with this drug, improvement in quality of life. Twenty five of the 93 patients (26.9%) studied were rendered seizure free with the addition of lamotrigine to their therapy. This was especially the case for patients with complex partial seizures, generalised seizures secondary to brain damage, primary generalised epilepsy and the Lennox Gastaut syndrome. Quality of life improvements were especially striking in patients with seizures secondary to brain damage and in the Lennox Gastaut Syndrome. Twenty eight patients ceased lamotrigine, 13 due to lack of effect and the remainder due to side effects. Lamotrigine is a potentially very useful anti-epileptic medication in persons with complex partial seizures, but also in primary generalised epilepsy, the Lennox Gastaut syndrome and especially in those individuals who have seizures subsequent to brain damage.     

Optimal use of lamotrigine in clinical practice: results of an open multicenter trial in refractory epilepsy]

The study was designed to evaluate optimal use of add-on lamotrigine in the treatment of children and adults with refractory epilepsy of any type. Because of the available evidence from controlled studies, indicating the large spectrum of action of lamotrigine, we designed this prospective study to investigate the efficacy and safety of lamotrigine in everyday clinical practice, to collect useful information on its action in specific epilepsy syndromes and on the clinical results of specific co-medications. We studied 566 patients with a diagnosis of refractory epilepsy of any type currently receiving stable conventional regimens of antiepileptic therapy. Efficacy analysis was limited to 510 patients (388 patients aged 12 years or more, 122 patients aged 2 to 12 years) for which the exact number of seizures could be evaluated. Seizure characteristics were: simple and/or complex partial seizures in 298 (58p. cent) patients, partial seizures with secondary generalisation in 85 (17p. cent), generalised seizures of any type in 226 (44 percent). Syndromic diagnosis was partial symptomatic or cryptogenic epilepsy in 302 patients (59 percent), generalised symptomatic or cryptogenic epilepsy in 116 (23 percent) and idiopathic generalised epilepsy in 50 (10 percent). The percentage of patients who achieved at least 50 percent reduction in the frequency of seizures was evaluated around 40p. cent for all epilepsy categories, and up to 61 percent in idiopathic generalised epilepsies. Response to treatment with lamotrigine was usually obtained by the end of titration (4 weeks) and remained stable at 48 weeks. Thirty-three patients (7 percent) remained seizure-free at 48 weeks. In the group of patients with partial epilepsy, 19p. cent presented a more than 75 percent reduction in seizure frequency. A more than 50 percent reduction in secondary generalisation of partial seizures was observed in 45 percent of the patients. Efficacy results were similar in both the adult and paediatric age groups. They were better for patients receiving valproate co-medication (45 percent of the responders) as compared to other co-medications (37 percent of the responders), suggesting a synergistic action. Safety has been evaluated for all the patients having received lamotrigine (n=566). The incidence of adverse events attributed to lamotrigine was similar to the results of controlled studies, with somnolence reported in 10p. cent, a cutaneous reaction in 8 percent and episodes of transitory diplopia in 8 percent. A cutaneous reaction was more frequent in patients receiving carbamazepine (10 percent) as compared to valproate comedication (5 percent). However, the adverse event was sufficiently serious to necessitate hospitalisation in 3 patients receiving valproate. Dose escalation was not respected in two. Rash was reversible in all of the patients following discontinuation of the drug. The results of this study contribute to the overall understanding of the spectrum of lamotrigine effectiveness across seizure types and epileptic syndromes. Lamotrigine was well tolerated in children and adults.     

Current treatment of myoclonic astatic epilepsy: clinical experience at the Children's Hospital of Philadelphia

PURPOSE: Myoclonic astatic epilepsy (MAE) is a generalized epilepsy of early childhood. Little is known about the use of newer antiepileptic treatments (AET) in MAE. The purpose of this study was to describe the characteristics, treatment, and outcome of a contemporary MAE cohort exposed to the new generation AET. METHODS: Charts of subjects with MAE treated between 1998 and 2005 were reviewed. RESULTS: Twenty-three subjects (19 boys), with a median (range) follow-up of 38 (2- 86) months were identified. Thirty-nine percent had a family history of epilepsy, and 39% had family history of febrile seizures. Age at seizure onset was a median of 36 (12-24) months. Initial EEG was normal in 30%. When seizures ceased, EEG background and epileptiform abnormalities persisted in 17 and 58%, respectively. On average, each subject was exposed to five AET. The most frequently used AET was valproate (83%). Seizure freedom occurred spontaneously in three subjects, with ethosuximide and levetiracetam in one each, valproate and lamotrigine in two each, topiramate in three and the ketogenic diet (KD) in five subjects. By 36 months after seizure onset, 67% achieved seizure freedom. At the last visit, 43% were developmentally normal, 52% had mild, and 5% had moderate cognitive disabilities. Time to seizure freedom did not correlate with cognitive outcome. CONCLUSIONS: The new generation of AET may offer significant benefit to children with MAE. The KD was the most effective AET in this series, and perhaps should be considered earlier in treatment.     

Clinical Science

Pregabalin Drug Interaction Studies: Lack of Effect on the Pharmacokinetics of Carbamazepine, Phenytoin, Lamotrigine, and Valproate in Patients with Partial Epilepsy Martin J. Brodie, Elaine A. Wilson, David L. Wesche, Christine W. Alvey, Edward J. Randinitis, Edward L. Posvar, Neil J. Hounslow, Nicola J. Bron, G.L. Gibson, and Howard N. Bockbrader Pregabalin (Lyrica) is a new drug that has been approved in the EU as add‐on treatment for partial seizures, and as treatment of peripheral neuropathic pain, in adults. Because many patients with partial seizures require more than one antiepileptic drug (AED) to achieve the best seizure control they can, it is important to determine whether new drugs for treating partial seizures may interact with commonly used AEDs. This paper reports the results of several drug–drug interaction studies of pregabalin and commonly used AEDs. In these studies, pregabalin was given to patients who were each taking one AED, either valproate, phenytoin, lamotrigine, or carbamazepine, to treat their epilepsy. Adding pregabalin to monotherapy with valproate, phenytoin, lamotrigine, or carbamazepine had no effect on the concentrations in the blood of any of these four drugs. Likewise, when concentrations of pregabalin in the blood were measured in these same patients, the concentrations were similar to those seen in the blood of subjects from earlier studies who had received pregabalin by itself. These findings indicate that pregabalin does not interact with any of these four common AEDs. The combinations of pregabalin with either valproate, phenytoin, lamotrigine, or carbamazepine were generally well tolerated by the patients in these studies, and when side effects did occur, they were typically mild to moderate and resolved quickly. Together, these studies demonstrate that pregabalin may be safely added to therapy with valproate, lamotrigine, phenytoin, or carbamazepine without concern for drug–drug interactions.     

Lamotrigine therapy of epilepsy in tuberous sclerosis

PURPOSE: Lamotrigine (LTG), a newer antiepileptic drug (AED), has activity against both partial-onset and generalized seizures. Its reported benefits for behavior, and its effectiveness in Lennox-Gastaut syndrome and other forms of refractory epilepsy, make it a logical choice for treatment of epilepsy in tuberous sclerosis complex (TSC). We present our experience with LTG therapy of epilepsy in 57 patients with TSC. METHODS: Patients fulfilled the diagnostic criteria for clinically definite TSC. LTG was initiated and increased until improvement in seizure frequency was noted, intolerable side effects occurred, or maximal doses were reached. Seizure frequency and behavioral changes were recorded during LTG therapy and compared with those prior to the introduction of LTG. RESULTS: Twenty-four (42%) were seizure free, and 21 (37%) had a >50% reduction in seizure frequency. Eighteen (32%) had subjectively improved behavior and/or alertness with daily activities. Thirty-eight (67%) had no change in this regard, whereas one (2%) became worse. Responders were more likely to not have a history of infantile spasms, and to have experienced only partial seizures (p < 0.05). Otherwise no phenotypic correlations with response were apparent. CONCLUSIONS: Among patients with TSC and epilepsy, LTG was effective and well tolerated, including as initial monotherapy. Improved alertness and behavior were apparent in many patients. The incidence of side effects is similar to that reported for other pediatric populations with symptomatic partial epilepsy. The usefulness of LTG in TSC may relate to an underlying defect of glutamatergic neurotransmission in partial epilepsy.     

Lamotrigine: single-dose pharmacokinetics and initial 1 week experience in refractory epilepsy

Twenty-three residential patients on chronic antiepileptic drugs (AEDs) were entered into an open study of 4 weeks duration. Baseline variables and seizure frequency were determined in the first week. All patients received a single dose of lamotrigine in the second week to determine single-dose pharmacokinetic parameters. Twenty patients then received daily or twice daily lamotrigine for a week. Post-treatment seizure frequency was observed for a further week. Patients taking liver enzyme inducing antiepileptic drugs showed a mean lamotrigine plasma elimination half-life (T1/2) of 14 h (+/- 7) (T1/2 of normal volunteers = 24 h) and those taking sodium valproate and an inducing AED showed a mean lamotrigine T1/2 of 30 h (+/- 10). The plasma concentrations of co-administered sodium valproate, phenytoin, carbamazepine, phenobarbitone and primidone were not altered by 1 week lamotrigine dosing. There was a significant reduction in complex partial seizures in the treatment week compared with baseline. Some patients showed a marked increase in seizure frequency on stopping lamotrigine. There was an increase in reports of drowsiness during lamotrigine administration, but there were no clinically significant changes in any safety measure.     

Influence of levetiracetam on the anticonvulsant efficacy of conventional antiepileptic drugs against audiogenic seizures in DBA/2 mice

Levetiracetam (LEV, [S]-alpha-ethyl-2-oxo-1-pyrrolidine acetamide) is a new antiepileptic that has been used as adjunctive therapy to treat patients with intractable epilepsy. Systemic administration of levetiracetam (2.5-30 mg/kg, intraperitoneally (i.p.)) was able to produce a dose-dependent decrease in DBA/2 audiogenic seizure severity score. In combination with conventional antiepileptic drugs, levetiracetam, 5mg/kg, i.p., which per se did not significantly affect the occurrence of audiogenic seizures in DBA/2 mice, potentiated the anticonvulsant activity of some antiepileptic drugs studied against sound-induced seizures in DBA/2 mice. The degree of potentiation induced by levetiracetam was greater, approximately twice, for carbamazepine, diazepam, felbamate, topiramate, gabapentin, and valproate, less for lamotrigine, phenobarbital and phenytoin. This increase was associated with a comparable impairment in motor activity; however, the therapeutic index of combined treatment of antiepileptic drugs with levetiracetam was more favourable than the combination with saline with the exception of lamotrigine, phenytoin and phenobarbital. Since levetiracetam did not significantly influence the total and free plasma and the brain levels of antiepileptics studied. In addition, levetiracetam did not significantly affect the hypothermic effects of the anticonvulsants tested. In conclusion, levetiracetam showed an additive anticonvulsant effect when administered in combination with some classical anticonvulsants, most notably carbamazepine, diazepam, felbamate, gabapentin, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.     

Antiepileptic drugs and mood stability.

This paper will discuss different definitions of the term "mood stabilizer" and highlight in detail the antiepileptic drugs carbamazepine, valproate and lamotrigine with respect to their relative strengths in stabilizing mood in bipolar patients. These drugs are heterogeneous in their mechanisms of action and in their efficacy to stabilize patients with epilepsy and the various mood states in bipolar disorder. Lamotrigine has obtained approval in several countries for the indication of preventing bipolar depressive episodes, which raises the question of differential efficacy of other antiepileptic drugs as mood stabilizers in the prevention of either depressive or hypo-/manic episodes. A Medline Search to 2006 was conducted for controlled acute and maintenance studies of the three scientifically and clinically most established antiepileptic drugs carbamazepine, valproate and lamotrigine. The medications discussed in this review only partly fulfill definitions of a mood stabilizer, and we suggest that future research should focus on combined treatment strategies.     

Ezogabine treatment of childhood absence epilepsy

Generalised‐onset absence seizures can be resistant to treatment with currently available antiepileptic drugs. Ezogabine (retigabine), a potassium channel opener, is approved for the treatment of focal‐onset seizures. This is a case report of an adult with childhood absence epilepsy whose daily absence seizures ceased with adjunctive ezogabine. A 59‐year‐old woman, with a history of typical absence seizures since the age of 6 years, had multiple seizures daily despite trials of over 11 antiepileptic drugs. While taking lamotrigine and zonisamide, ezogabine at 50 mg daily was added. The dose was slowly increased and once a total dose of only 200 mg/day was reached, she became seizure‐free for three months. After subsequently discontinuing zonisamide, absence seizures returned. Further increasing the ezogabine to 400 mg/day, in addition to lamotrigine, did not restore seizure freedom, but adding back zonisamide at half dose again reduced their frequency. Ezogabine at low dose, added to lamotrigine and zonisamide, led to sustained absence seizure freedom. The return of seizures after zonisamide discontinuation suggests that the seizure freedom may have been the result of the different mechanisms of action of the antiepileptic drugs.     

Efficacy and tolerability of lamotrigine in Juvenile Myoclonic Epilepsy in adults: A prospective,unblinded randomized controlled trial

PurposeControlled randomized studies recommending the clinical use of lamotrigine in adult populations with the diagnosis of Juvenile Myoclonic Epilepsy are still lacking. To compare the efficacy and tolerability of lamotrigine versus valproate in adult patients with JME.MethodsThis was a prospective, randomized, controlled, pragmatic, long-term and open-label treatment trial. Patients were randomized to use valproate or lamotrigine. The primary end points of the study were: (1) time from randomization to treatment failure (withdrawal); (2) time from randomization to seizures remission. Secondary ending points were: (1) frequency of clinically important adverse events and (2) change in the QOLIE-31 after randomization. The definition of seizure remission was based on disappearance of all seizure types and EEG discharges.ResultsWe found that the time to withdraw treatment after randomization was not significantly different in lamotrigine and valproate groups. Long-term seizures freedom was equal in the both groups of the trial; only 8 (19.1%) patients randomized to lamotrigine and 6 (19.4%) randomized to valproate were not seizure free after 4 months of treatment. Between 17.03% (lamotrigine) and 35.3% (valproate) of patients reported adverse reactions at some point in the intention-to treat study (p = 0.07). All subscales of the QOLIE-31 questionnaire, except that related to side effects of medication, improved more than 5 points with respect to baseline period in both groupsConclusionLamotrigine is effective in adult patients with Juvenile Myoclonic Epilepsy and better tolerated than valproate, although the incidence of idiosyncratic reactions could be a cause of concern.