Lamotrigine Treatment Research Articles

Lamotrigine-induced rash - worth a rechallenge*

The only serious adverse event associated with lamotrigine (LTG) treatment is a hypersensitivity reaction primarily presenting as a rash. Despite this concern, LTG is an antiepileptic drug (AED) with one of the most favorable efficacy/tolerability ratio compared with the new as well as the old AEDs. Thus, this study aimed to evaluate the results of rechallenge with LTG after the initial rash. A total of 688 patients (350 as monotherapy, and 338 as add-on therapy) with either idiopathic generalized epilepsy or focal epilepsy were treated with LTG. The patients with LTG-induced rash were rechallenged to LTG. The dosage schedule was: 5 mg every day or every second day for 14 days, increased by 5 mg every 14th day to 25 mg a day. After achieving the daily dosage of 25 mg/day, the up-titration was completed following the current guidelines. A total of 52 patients developed a rash. The LTG-induced rash occurred in 6%, where 12 (1.8%) developed a rash shown to be coincidentally associated with the initiation of LTG therapy. In their cases LTG was continued with success without intermission. Nineteen (38%) of the initial cohort were rechallenged with LTG, with a success rate of 84%. This study is the first one to provide a successful recipe verified in time for the rechallenge with LTG after the initial drug-induced rash. Importantly, the concurrent use of valproate (VPA) was not found in this study to represent an additional risk factor for the occurrence of the rash during rechallenge with LTG. Our results agree with previous findings that women are more likely to develop the rash (P < 0.009).

Recurrent Severe Aseptic Meningitis after Exposure to Lamotrigine in a Patient with Systemic Lupus Erythematosus

Recurrent Severe Aseptic Meningitis after Exposure to Lamotrigine in a Patient with Systemic Lupus Erythematosus

Effects of acute and chronic lamotrigine treatment on basal and stimulated extracellular amino acids in the hippocampus of freely moving rats

The antiepileptic drug lamotrigine (LTG) is a relatively novel anticonvulsant frequently used in polytherapy and increasingly in monotherapy. LTG is believed to act by reducing excitatory glutamate (GLU) release due to an inhibition of Na + channels. In the present study, we have investigated the effects of acute and chronic (up to 21 days) treatment with LTG on basal and either veratridine- or KCl-stimulated release of aspartate (ASP), GLU, taurine (TAU) and GABA in the hippocampus of freely moving rats using microdialysis. Additionally, we have measured LTG concentrations in the plasma, whole brain and extracellular fluid of rats at the same time points. LTG significantly reduced basal ASP and GLU but only at the highest dose used (20 mg/kg) and was entirely without effect on basal TAU or GABA. When either veratridine or 100 mM KCl were added to the infusion medium amino acid release was evoked although the extent of this varied from one amino acid to another. LTG (10 mg/kg) reduced veratridine-evoked release of all four amino acids studied, although this was most marked in the case of GLU. LTG had no effect on KCl-stimulated amino acid release. When given for up to 21 days (2×5 mg/kg/day), LTG had no effect on basal amino acid levels. In contrast, LTG demonstrated over the time period studied an increasingly inhibitory effect on veratridine-evoked amino acid release. This effect of the drug was proportionally much greater in the case of GLU than for the other three amino acids studied. Measurement of plasma, whole brain tissue and extracellular LTG showed that in each of these compartments, it had reached an apparent steady state within 4 days of commencement of treatment and appeared to mirror the neurochemical changes measured. Our estimate of plasma LTG indicates that during chronic study, this was well within the therapeutic range, suggesting that the current neurochemical observations are clinically relevant.

Placebo-controlled trial of lamotrigine added to conventional and atypical antipsychotics in schizophrenia

Lamotrigine, a novel anticonvulsant drug having modulatory effects on glutamatergic neurotransmission, improves mood and cognition parameters in bipolar disorder. Recent studies suggest that when added to clozapine, lamotrigine treatment may result in significant positive symptoms reductions in schizophrenia. Similar effects were not observed in an open trial in which lamotrigine was used as adjuvant to nonclozapine antipsychotics. Thirty-eight treatment-resistant schizophrenia inpatients receiving conventional and atypical antipsychotics enrolled in a 10-week, double-blind, placebo-controlled study, in which they were randomized in a 2:1 ratio to receive adjuvant treatment with lamotrigine, gradually titrated to a 400 mg/day dose, or placebo. Of these, 31 completed the trial. Measures of clinical efficacy and side effects were determined every other week. Serum levels of amino acids were assessed at the beginning and end of the study. In primary last observation carried forward analysis, no statistically significant between-group differences were observed; however, the completers' analyses revealed that lamotrigine treatment resulted in significant (p < or = .05) reductions in positive and general psychopathology symptoms, as measured by the Positive and Negative Syndrome Scale. No significant differences in lamotrigine effects were noted between conventional versus atypical antipsychotics. Lamotrigine treatment was well tolerated, and glutamate serum levels remained stable throughout the study. These preliminary findings 1) support the hypothesis that lamotrigine adjuvant treatment may improve positive symptoms and general psychopathology in schizophrenia, 2) suggest that beneficial effects may be achieved when lamotrigine is added to both conventional and atypical antipsychotics, and 3) warrant additional, larger scale trials.

Effect of lamotrigine treatment on epileptogenesis: an experimental study in rat

Prevention of epileptogenesis in patients with acute brain damaging insults like status epilepticus (SE) is a major challenge. We investigated whether lamotrigine (LTG) treatment started during SE is antiepileptogenic or disease-modifying. To mimic a clinical study design, LTG treatment (20 mg/kg) was started 2 h after the beginning of electrically induced SE in 14 rats and continued for 11 weeks (20 mg/kg per day for 2 weeks followed by 10 mg/kg per day for 9 weeks). One group of rats ( n=14) was treated with vehicle. Nine non-stimulated rats with vehicle treatment served as controls. Outcome measures were occurrence of epilepsy, severity of epilepsy, and histology (neuronal loss, mossy fiber sprouting). Clinical occurrence of seizures was assessed with 1-week continuous video-electroencephalography monitoring during the 11th (i.e. during treatment) and 14th week (i.e. after drug wash-out) after SE. LTG reduced the number of electrographic seizures during SE to 43% of that in the vehicle group ( P<0.05). In the vehicle group, 93% (13/14), and in the LTG group, 100% (14/14) of the animals, developed epilepsy. In both groups, 64% of the rats had severe epilepsy (seizure frequency >1 per day). The mean frequency of spontaneous seizures, seizure duration, or behavioral severity of seizures did not differ between groups. The severity of hippocampal neuronal damage and density of mossy fiber sprouting were similar. In LTG-treated rats with severe epilepsy, however, the duration of seizures was shorter (34 versus 54 s, P<0.05) and the behavioral seizure score was milder (1.4 versus 3.4, P<0.05) during LTG treatment than after drug wash-out. LTG treatment started during SE and continued for 11 weeks was not antiepileptogenic but did not worsen the outcome. These data, together with earlier studies of other antiepileptic drugs, suggest that strategies other than Na +-channel blockade should be explored to modulate the molecular cascades leading to epileptogenesis after SE.

Lamotrigine in treatment-resistant schizophrenia: a randomized placebo-controlled crossover trial

Background There is no evidence from randomized, controlled trials that demonstrate effectiveness for any pharmacological treatment in clozapine-resistant schizophrenia. Since the introduction of chlorpromazine, all antipsychotics with proven efficacy on positive symptoms have been dopamine antagonists, but recent experimental data suggest that ketamine-induced positive schizophreniform symptoms in healthy subjects can be controlled by a glutamate antagonist lamotrigine. The hypothesis tested was that lamotrigine is more effective than placebo in the treatment of positive schizophrenic symptoms when combined with clozapine. Methods Thirty-four hospitalized treatment-resistant patients having chronic schizophrenia participated in a double-blind, placebo-controlled, 14-week, crossover trial where 200 mg/day lamotrigine was gradually added to their ongoing clozapine treatment. Clinical assessments were made by the Positive and Negative Syndrome Scale at the beginning and end of each treatment period. Results In intention-to-treat analysis, lamotrigine treatment was more effective in reducing positive (effect size .7, p = .009) and general psychopathological (effect size .6, p = .030) symptoms, whereas no improvement was observed in negative symptoms. Conclusions These results provide the first evidence from a randomized controlled trial of an effective pharmacological treatment with an anticonvulsant agent in treatment-resistant schizophrenia and indicate that both positive and general psychopathological symptoms in patients with schizophrenia can be controlled by a drug that is not a dopamine antagonist. The results are in line with previous experimental data suggesting that excessive glutamate neurotransmission contributes to the positive symptoms of schizophrenia.

Relationship between lamotrigine oral dose, serum level and its inhibitory effect on CNS: insights from transcranial magnetic stimulation

The antiepileptic drug lamotrigine (LTG) is known to reduce cortical excitability evaluated by transcranial magnetic stimulation (TMS). We investigated the relationship between LTG oral dosages, serum levels and inhibitory effects on resting motor threshold (RMT), a parameter of motor system excitability assessed by TMS. In a randomized, placebo-controlled crossover study 16 male volunteers received 325 mg LTG as a single dose, as bi-hourly graded cumulative dose, or placebo. RMT and serum levels were measured before and after 2–8 h. With single dose, RMT elevation showed a poor but significant correlation to serum levels. With graded dose, serum levels as well as RMT increased dose-dependently with significant ( P<0.0001) linear correlation. However, detailed comparison showed a high inter-individual variability in the relationship resembling a sigmoid correlation. Different mechanisms besides the sodium-channel blockage as the main mode of action of LTG are discussed to explain the diversity of individual dose–response relationships. Provided that the RMT elevation reflects the antiepileptic potential of LTG, TMS may be developed as a tool to monitor interindividual response of epilepsy patients to LTG treatment as well as to explore efficacy of other antiepileptic drugs with similar mode of action.

Improvement of toxic epidermal necrolysis after the early administration of a single high dose of intravenous immunoglobulin

Toxic epidermal necrolysis (TEN) is a severe disease often induced by drugs. Treatment is controversial, although intravenous immunoglobulins (IVIGs) have been effective. To report the case of a child with TEN after lamotrigine treatment, who improved 24 hours after IVIG administration. Sequential blood and blister fluid samples were obtained for flow cytometry and reverse transcriptase-polymerase chain reaction analyses. The first blood sample, taken before IVIG administration, showed normal levels of lymphocyte subsets and CLA (4.0%) but high levels of activated lymphocytes (CD69) (18.0%). After treatment, the CLA+, CD69+, and memory cells increased until day 7, decreasing to normal values at days 15 and 30. In the blister fluid samples, taken on day 1, there were high levels of CD8+ (70.2%; CD4/CD8 ratio, 1:5), CLA+ (18.8%), and CD69+ (70%) cells, decreasing 24 hours after IVIG administration. In the blood samples, there was a Th1 cytokine pattern initially, tending to Th0 with time. Perforin, granzyme B, and Fas ligand were only observed before IVIG administration. A single high dose of IVIG interrupted the progression of skin disease and reduced the expression of the apoptotic markers. The immunologic changes, first seen in blister fluid and remaining several days in peripheral blood, indicate that T cells were first recruited to the skin and then recirculated to blood.

Gonadal morphology and sex hormones in male and female Wistar rats after long-term lamotrigine treatment

Drug-induced disturbances in reproductive hormones and gonadal morphology have been observed both in patients with epilepsy and in non-epileptic animals. Less is known about the influence of newer antiepileptic drugs including lamotrigine on reproduction. Lamotrigine is now increasingly used both in epilepsy and psychiatric disorders. Sixty-five Wistar rats were fed by gastric tube either 5 mg kg −1 lamotrigine solution (males=15, females=20) or 0 (vehicle control, males=15, females=15) twice daily for 90 days. In males, no significant differences were found in body or testicular weight. Testicular atrophy was observed in one control animal and in two of the rats receiving lamotrigine. No morphological changes were seen in the other organs investigated (liver, kidney, pancreas, brain, lymphatic tissue, heart). None of the animals showed over-expression of p53. No significant differences were observed between the control rats and the male rats receiving lamotrigine regarding testosterone, FSH and LH. In females, no changes in ovarian morphology or alterations in other tissues were observed. Serum testosterone, FSH, LH, insulin and progesterone remained unchanged in the lamotrigine treated animals, while serum estrogen was significantly reduced.

Effect of Lamotrigine on Mood and Cognition in Patients Receiving Chronic Exogenous Corticosteroids

Mood changes, cognitive deficits, and psychosis have been reported during corticosteroid therapy. However, minimal data are available on the treatment of these side effects. This pilot study examined the effect of 12 weeks of open-label lamotrigine treatment (dose: mean=340 mg/day, SD=65) on mood and cognition in five patients receiving prescription corticosteroids continuously for at least 6 months before study entry. The participants showed significant improvement in cognition with lamotrigine. Two subjects who met criteria for a current major depressive episode at baseline had baseline-to-exit reductions in scores on the Hamilton Depression Rating Scale of more than 20 points. These pilot data suggest that lamotrigine may be associated with improved mood and performance on cognitive tasks in steroid-treated patients. Larger controlled trials are needed to confirm these preliminary findings.

Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy

Background: Valproate is used widely for the treatment of epilepsy but has been associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. The mechanism for these associations is unknown, but they have been hypothesized to be secondary to valproate-associated weight gain. This study was conducted to test the hypothesis that the antiepileptic drug lamotrigine, which also has a broad spectrum of anti-seizure efficacy, would not be associated with endocrine abnormalities and would not cause weight gain. Objective and Methods: This open-label, cross-sectional study compared (1) endocrine and lipid measures during the early follicular phase of the menstrual cycle; (2) prevalence of menstrual disorders (from patient diaries recorded over three cycles); and (3) body weight of women with epilepsy on lamotrigine monotherapy ( n=119) with those on valproate monotherapy ( n=103) for <5 years. Results: Mean total serum testosterone and androstenedione levels were higher ( P<0.02) in the valproate group compared with the lamotrigine group. More lamotrigine patients (87%) than valproate patients (77%) reported regular menstrual cycles at the Screening Visit. The prevalence of anovulation did not differ between lamotrigine and valproate. Mean HDL cholesterol levels were higher ( P<0.01) with lamotrigine compared with valproate as were LDL and total cholesterol levels ( P<0.05). Mean total insulin levels did not significantly differ between the groups. Whereas mean body weight in lamotrigine patients did not differ between the time lamotrigine treatment was initiated and the Study Visit, mean weight in valproate patients increased by 3.7 kg. Conclusions: Compared with lamotrigine monotherapy, valproate monotherapy was associated with weight gain and higher androgen levels in women with epilepsy. These data suggest that the hyperandrogenism observed in some women using valproate for epilepsy may be secondary to drug therapy. Lamotrigine monotherapy may be more appropriate than valproate for women in whom reproductive endocrine or metabolic abnormalities are potential concerns, i.e. women with concerns about weight gain, diabetes, hirsutism, polycystic ovary syndrome, menstrual dysfunction or infertility.

Lamotrigine in Patients With Bipolar Disorder and Cocaine Dependence

Bipolar disorder is associated with the highest substance abuse rates of any psychiatric illness. Therefore, treatments that stabilize mood and decrease drug use or cravings are of great interest. Open-label lamotrigine was examined in 30 outpatients with DSM-IV bipolar disorder and cocaine dependence. Lamotrigine was either added to existing medication regimens or used as monotherapy. Lamotrigine was started at a dose of 25 mg/day (12.5 mg/day in those taking valproic acid) and titrated to a maximum dose of 300 mg/day. Subjects received a baseline evaluation including a structured clinical interview and weekly assessments for 12 weeks with the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), and Cocaine Craving Questionnaire (CCQ). At each appointment, a urine sample was obtained, and participants reported drug use during the previous week. The subjects consisted of 13 men and 17 women with cocaine dependence and bipolar I disorder (N = 22), bipolar II disorder (N = 7), or bipolar disorder not otherwise specified (N = 1), with a mean +/- SD age of 35.4 +/- 7.2 years. Data were analyzed using the last observation carried forward on all subjects who completed the baseline evaluation and at least 1 postbaseline assessment. Significant improvement was observed in HAM-D, YMRS, and BPRS scores (p < or =.02). Cravings also significantly decreased as measured by the CCQ (p <.001). Dollar amount spent on drugs decreased nonsignificantly. Lamotrigine was well tolerated, with no subjects discontinuing due to side effects. Lamotrigine treatment was well tolerated in this sample and associated with statistically significant improvement in mood and drug cravings but not drug use. The findings suggest that larger controlled trials of lamotrigine are needed in this population.

Lamotrigine: a review of its use in bipolar disorder.

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. 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.

Beneficial behavioural effects of lamotrigine in traumatic brain injury

Anti-convulsant medications have been employed to treat behavioural disorders resulting from traumatic brain injury (TBI). However, there is a paucity of literature investigating the use of lamotrigine to treat aggression and agitation in patients with TBI. In a single case study design, the present study examined the effectiveness of lamotrigine to treat aggressive and agitated behaviour in a 40-year-old male who sustained a severe TBI. A substantial decrease in problematic behaviours and a significant improvement in neurobehavioural functioning were observed after lamotrigine treatment. This case study provides some support for the use of lamotrigine to treat aggression and agitation in patients with a TBI. Further research is needed to examine the relationship between lamotrigine and functional outcome after TBI.

Valproic acid and lamotrigine treatment during pregnancy: The risk of chromosomal abnormality

A baby born to an epileptic mother had dysmorphological features associated with 47,XXX karyotype. The mother had been treated with valproic acid (1800 mg per day) and lamotrigine (100 mg per day) throughout pregnancy. Dysmorphological features detected in baby were intrauterine growth retardation, hypertelorism, flattened nasal bridge, low set malformed auriculas, micrognathia, very small an bow-shaped mouth with thin upper lip, cleft palate, arachnodactyly, camptodactyly, secundum atrial septal defect, bilateral hammer toes and decreased creases on the soles. At 6 months old she showed motor retardation. The molecular analysis of parents revealed that extra X chromosome was inherited from the mother. In this case whether the dysmorphological features and 47,XXX karyotype were caused by lamotrigine and valproic acid treatment during pregnancy or coincidence is in question.

Improvement in depression associated with partial epilepsy in patients treated with lamotrigine

Interictal depression is common in patients with epilepsy and it significantly impacts quality of life. Previous studies indicate that lamotrigine may have antidepressant properties. Thirteen adults with uncontrolled partial seizures and concomitant depression were evaluated using measures of depression [Montgomery and Asberg Depression Rating Scale (MADRS) and the MMPI Depression Scale] and anxiety [Spielberger’s State–Trait Anxiety Inventory (STAI)] to test the effects of lamotrigine on mood. Evaluations after 5 weeks and again after 3 months of lamotrigine treatment demonstrated significant improvement in depression and anxiety. Mean MADRS overall scores were significantly lower than pretreatment baseline at the 5-week and 3-month evaluations. The mean MMPI Depression score was significantly lower than baseline at the 3-month evaluation. State anxiety scores were significantly reduced from baseline after 5 weeks, but not at 3 months, whereas Trait anxiety scores were reduced from baseline at the 5-week and 3-month evaluations.

Therapeutic Drug Monitoring of Lamotrigine in Patients Suffering from Resistant Partial Seizures

Sixty patients, all potential candidates for ongoing lamotrigine (LTG) treatment as add-on therapy for resistant partial seizures and receiving carbamazepine (CBZ) and/or valproate (VPA) treatment, were submitted to therapeutic drug monitoring (TDM). The aim was to evaluate the possible relation between serum levels and the clinical effect of LTG, to verify whether CNS toxicity has to be considered the result of a pharmacokinetic or a pharmacodynamic interaction with CBZ, and to investigate whether possible changes in the clinical response during long-term treatment are dependent on LTG serum level variations. Sixteen patients achieved complete control, 26 a ≧50% reduction in seizures, the remainder did not respond. Mean LTG serum concentrations were higher in responders than in nonresponders, the difference being statistically insignificant. The best results were observed in VPA-cotreated patients with the highest LTG blood levels. CNS toxicity occurred after giving LTG to subjects who subsequently developed the highest LTG concentrations, whereas CNS toxicity seemed unrelated to CBZ and CBZ-epoxide serum concentrations. No decrease in LTG, CBZ and VPA serum levels was observed even in patients showing a reduction in the response during long-term treatment.

Lack of an effect of topiramate on lamotrigine serum concentrations.

Pharmacokinetic interactions between the older antiepileptic drugs (AEDs) and topiramate (TPM) were assessed during the clinical development of this drug. Lamotrigine (LTG) has become established as an important new drug in treating a wide spectrum of seizure types, but there are no published data on whether LTG serum concentrations change when TPM is added to treatment. Escalating doses of TPM were added to stable LTG treatment in 24 young patients (8-21 years) with epilepsy. Blood samples taken before the morning dose were collected for drug-concentration measurement in all patients before starting treatment with TPM and after stabilisation at each dose escalation. Several patients had been maintained on unchanged therapy with drug-concentration monitoring for many months before introducing TPM, and a sequence of baseline LTG serum concentrations were available on these patients. The mean of all baseline LTG concentrations for the group as a whole was 10.4 +/- 4.4 mg/L compared with 9.7 +/- 4.3 mg/L after addition of TPM. A comparison of last baseline LTG concentration with first test LTG concentration (i.e., after 2 weeks' TPM treatment) gave mean values of 10.7 +/- 4.7 and 10.8 +/- 4.6 mg/L, respectively. The mean LTG concentration for patients while taking their highest TPM dose was 9.5 +/- 4.3 mg/L. The analysis-of-variance modeling for the effect of TPM on LTG concentration yielded a mean LTG concentration ratio (with TPM vs. without TPM) of 94.2%, with a 90% confidence interval of 89.5-99.1%. TPM did not cause a significant change in LTG serum concentration in this group of patients.

Lamotrigine and Landau-Kleffner Syndrome - Two Cases

The Landau-Kleffner syndrome (LKS) is a rare and intractable disorder with a combination of acquired aphasia and epileptic discharges. Recent treatments comprise various strategies of uncertain efficacy. We report on two developmentally retarded boys (9.7 and 11.4 years old) admitted to our hospital with the diagnosis of elective mutism. In both cases epileptic seizures were first observed at the age of 4 years. Findings of CT. MRT, and CSF were not significant. Their seizures were polymorphic, including multiple absences and secondary generalised tonic-clonic despite constant polytherapy with antiepileptic drugs (AEDs: carbamazepine - CBZ and valproate - VPA, previously sultiam in the first case and phenobarbital in the second). Upon admission to our clinic, we first replaced CBZ or phenobarbital with increasing doses of lamotrigine (LTG) added on to valproate. The initial dose of LTG in both cases was 12.5 mg/day. The EEG normalised at a dose of 100mg/day six weeks after initiation of LTG treatment and the aphasic symptoms improved daily. The boys have been seizure free and have noted no side effects since initiation of LTG monotherapy. Recovery has continued while on LTG monotherapy. We conclude that LTG either as add-on or as monotherapy could become first-line AED in the treatment of LKS.

The effects of lamotrigine on sleep in patients with epilepsy.

The older antiepileptic drugs (AEDs) have a variety of effects on sleep, including marked reduction in REM, slow-wave sleep (SWS) and sleep latency, and increased percentage of light sleep. The effects of the newer AEDs on sleep are unknown. Our purpose was to study the effect of lamotrigine (LTG) on sleep. Ten adults with focal epilepsy, in whom the decision was made to add LTG to either phenytoin (PHT) or carbamazepine (CBZ) for control of seizures, were the subjects of this study. Patients underwent pre- and posttreatment polysomnography (PSG) and completed sleep questionnaires. Polygraphic variables and Epworth Sleepiness Scale (ESS) scores, a subjective measure of sleep propensity, were compared by using the Wilcoxon sign rank test. Seven patients were taking CBZ, and three were treated with PHT. All subjects were titrated to an LTG dose of 400 mg/day. Treatment with LTG produced a significant decrease in SWS and an increase in stage 2 sleep percentage. No significant difference in ESS or any of the other polygraphic variables was observed. However, LTG treatment was associated with a reduction in arousals and stage shifts and an increase in REM periods. No subjects reported insomnia with treatment. LTG appears to be less disruptive to sleep than some of the older AEDs.