Lamotrigine Monotherapy Research Articles

Ictal Source Locations and Cortico-Thalamic Connectivity in Childhood Absence Epilepsy: Associations with Treatment Response.

Childhood absence epilepsy (CAE), the most common pediatric epilepsy syndrome, is usually treated with valproic acid (VPA) and lamotrigine (LTG) in China. This study aimed to investigate the ictal source locations and functional connectivity (FC) networks between the cortices and thalamus that are related to treatment response. Magnetoencephalography (MEG) data from 25 patients with CAE were recorded at 300Hz and analyzed in 1-30Hz frequency bands. Neuromagnetic sources were volumetrically scanned with accumulated source imaging. The FC networks between the cortices and thalamus were evaluated at the source level through a connectivity analysis. Treatment outcome was assessed after 36-66months following MEG recording. The children with CAE were divided into LTG responder, LTG non-responder, VPA responder and VPA non-responder groups. The ictal source locations and cortico-thalamic FC networks were compared to the treatment response. The ictal source locations in the post-dorsal medial frontal cortex (post-DMFC, including the medial primary motor cortex and the supplementary sensorimotor area) were observed in all LTG non-responders but in all LTG responders. At 1-7Hz, patients with fronto-thalamo-parietal/occipital (F-T-P/O) networks were older than those with fronto-thalamic (F-T) networks or other cortico-thalamic networks (p = 0.000). The duration of seizures in patients with F-T-P/O networks at 1-7Hz was longer than that in patients with F-T networks or other cortico-thalamic networks (p = 0.001). The ictal post-DMFC source localizations suggest that children with CAE might experience initial LTG monotherapy failure. Moreover, the cortico-thalamo-cortical network is associated with age. Finally, the cortico-thalamo-cortical network consists of anterior and posterior cortices and might contribute to the maintenance of discharges.

Interaction between ABCG2 421C>A polymorphism and valproate in their effects on steady-state disposition of lamotrigine in adults with epilepsy.

To investigate the impact of glucuronidation enzyme (UGT1A4*3 142T>G, UGT1A4*2 70C>A, UGT2B7 -161C>T) and transporter (MDR1/ABCB1 1236C>T, ABCG2 421C>A) polymorphisms on steady-state disposition of lamotrigine and on the lamotrigine-valproate interaction. Adults with epilepsy on lamotrigine monotherapy (n=131) or lamotrigine + valproate treatment (n=74) were genotyped and steady-state lamotrigine and valproate morning troughs were determined as a part of routine therapeutic drug monitoring. No effect of UGT and MDR1/ABCB1 polymorphisms was observed. In the entire cohort, ABCG2 421A allele had no effect however an interaction between the variant allele and valproate was observed: (i) in lamotrigine-only patients, variant allele (vs. wild type homozygosity) was independently (adjustments: age, sex, body mass index, lamotrigine dose, other polymorphisms) associated with mildly lower lamotrigine troughs [geometric means ratio (GMR)=0.76, 95% confidence interval (CI) 0.59-0.98], whereas in lamotrigine + valproate patients it was associated with higher troughs (GMR=1.72, 95%CI 1.14-2.62); (ii) valproate cotreatment was overall associated with markedly higher troughs vs. lamotrigine monotherapy (GMR=3.49, 95%CI 2.73-4.44), but more so in variant allele carriers (GMR=5.24, 95%CI 3.38-8.15) than in wild type homozygotes (GMR=2.32, 95%CI 1.89-2.83); (iii) variant allele effects in two treatment subsets and valproate effects in two genotype subsets differed by 2.36-fold (95%CI 1.39-3.67); (iv) increase in lamotrigine troughs associated with increasing valproate troughs was greater in variant allele carriers than in wild type homozygotes, i.e. variant allele effect increased with increasing valproate troughs. This study is first to indicate a potentially relevant interaction between ABCG2 421C>A polymorphism and valproate in their effects on lamotrigine disposition.

Levetiracetam and lamotrigine effects as mono- and polytherapy on bone mineral density in epileptic patients.

The purpose of this study was to determine the effect of lamotrigine (LTG) and levetiracetam (LEV) as mono- and polytherapy on biochemical markers of bone turnover and bone mineral density in Egyptian adult patients with epilepsy. Forty-eight patients were divided into four groups: two received monotherapy of either LTG or LEV, and the other two groups received polytherapy comprising (valproate [VPA] + LTG or VPA + LEV). Thirty matched healthy participants were included in the study. Participants completed a nutritional and physical activity questionnaire. Biochemical markers of bone and mineral metabolism and bone mineral density of the lumbar spine were measured at baseline and at six months. In the LEV monotherapy group, the bone formation markers showed a significant decrease in serum alkaline phosphatase and serum osteocalcin levels while the bone resorption marker showed a significant increase in urinary deoxypyridinoline levels. After six months of treatment, bone mineral density showed a significant decrease in all treated groups, while among monotherapy groups, this significant decrease was more prevalent in the LEV monotherapy group compared with the LTG monotherapy group. Furthermore, there was significant negative correlation between urinary deoxypyridinoline levels and bone mineral density in the LEV monotherapy group. Using new generation antiepileptics, LEV monotherapies and polytherapy showed harmful effects on bone but LTG did not.

Comparison of lamotrigine and oxcarbazepine monotherapy for pediatric focal epilepsy: An observational study

PurposeOxcarbazepine is known as an effective first-line monotherapy for pediatric focal epilepsy. Lamotrigine has also been reported to have similar efficacy to and better tolerability than carbamazepine. Therefore, the effectiveness of oxcarbazepine and lamotrigine monotherapies was compared in patients with pediatric focal epilepsy. MethodA total of 116 patients in pediatric patients with partial epilepsy received lamotrigine (n = 43) or oxcarbazepine (n = 73) monotherapy. The clinical characteristics, seizure outcomes, reasons for drug discontinuation, retention rate and adverse effects were evaluated for each drug. ResultsOxcarbazepine was more commonly used than lamotrigine (69/73 vs. 23/43) as initial monotherapy. Lamotrigine showed better efficacy than oxcarbazepine in terms of the seizure outcome more than 12 months (P<0.05). Oxcarbazepine and lamotrigine showed similar tolerability in terms of the retention rate, drug discontinuation and adverse effects. The rates of successful discontinuation were similar for patients receiving these drug as initial monotherapy (P > 0.05). The seizure outcome was much better for lamotrigine than for oxcarbazepine in patients with normal MRI findings and normal development (P = 0.001, P = 0.01). The retention rate was high in patients with MRI abnormalities or developmental delay in the lamotrigine group. The choice of lamotrigine was the only independent variable that predicted a seizure-free state, even after correcting for clinical variables (OR = 4.80, P = 0.013). ConclusionsLamotrigine was superior to oxcarbazepine monotherapy because of its greater effectiveness in treating pediatric focal epilepsy. Lamotrigine can be selected as a first-line monotherapy in patients with or without abnormal MRI findings or delayed development.

Long-term efficacy and safety of lamotrigine monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures: An open-label extension study

PurposeTo investigate the efficacy and safety of long-term lamotrigine (LTG) monotherapy in Japanese and South Korean pediatric patients with newly diagnosed typical absence seizures. MethodsSix Japanese patients and one South Korean patient were enrolled in the extension phase of the study after completing the 12-week maintenance phase of an open-label clinical study of LTG monotherapy. During the extension phase, patients underwent efficacy and safety evaluation every 12 weeks. ResultsOf the seven patients, six patients completed the extension phase. The seizure-free rate confirmed by hyperventilation (HV)-electroencephalography ranged from 71.4% to 100.0% at each visit up to Week 168 of the extension phase. Similar effects were confirmed by HV-clinical signs and seizure diaries. Although no unexpected adverse events were observed, one Japanese patient was withdrawn from the extension phase due to mild drug-related rash developed 842 days after the start of LTG. ConclusionAlthough the number of patients is limited, long-term LTG monotherapy appeared to be effective and generally well tolerated in Japanese and South Korean pediatric patients with typical absence seizures.

Comparative efficacy of unique antiepileptic drug regimens in focal epilepsy: An exploratory study

ObjectiveTo compare efficacy of unique antiepileptic drug (AED) polytherapy regimens among patients with focal epilepsy. MethodsFrom a longitudinal study of AED treatment, we identified patients with active focal epilepsy who had attempted at least two unique AED regimens (mono-, duo-, or tri-therapy). Efficacy was defined as the presence of at least one six-month period of continuous seizure freedom during exposure to a regimen. To control for individual variations in response and epilepsy severity, we used within-patient comparison approaches, in which we: 1) compared head-to-head unique regimens tried within the same patients; 2) compared one regimen versus aggregate of other regimens attempted in that patient; and 3) compared aggregated monotherapy versus polytherapy regimens. Results757 patients met our criteria and had collectively attempted 170 unique regimens. In the head-to-head analysis, lamotrigine monotherapy was more effective than phenytoin monotherapy. Two regimens were more effective than the aggregate of other regimens attempted: levetiracetam/lamotrigine duotherapy and lamotrigine monotherapy. Two other regimens exhibited slightly better efficacy but did not reach statistical significance: clobazam/levetiracetam/lamotrigine and levetriacetam/oxcarbazepine. Patients who previously attempted at least four regimens had slightly better outcomes on polytherapy than monotherapy, though this was not significant. SignificanceWe identified two unique regimens more likely to be associated with ≥6 months of seizure freedom: levetiracetam/lamotrigine duotherapy and lamotrigine monotherapy. Polytherapy may be an effective alternative to monotherapy for patients with focal epilepsy and persistent seizures.

Time course of reversal of valproate-mediated inhibition of lamotrigine

PurposeConversion to lamotrigine (LTG) monotherapy from sodium valproate (VPA) is complicated by the robust pharmacokinetic interaction between the two AEDs. This study examined changes in LTG serum concentrations immediately following VPA discontinuation. MethodsTen healthy female and male adult subjects were initiated on LTG (Lamictal) 10 mg orally every morning for 30 days and VPA (Depakote ER) 500 mg orally every morning for 14 days. Morning trough (pre-dose) venous blood samples were obtained for determination of LTG and VPA concentrations on study days 14, 15, 16, 18, 20, 22, 24, 26, 28, and 30. Following the collection of the blood sample on day 15, VPA was discontinued. ResultsDespite stable LTG dosage serum concentrations on study day 20, 22, 24, 26, and 28, all were significantly lower compared to baseline (p < 0.05). ConclusionsThese observations demonstrate that the pharmacokinetic interaction between LTG and VPA is reversible, and that de-inhibition appears to follow a predictable time course. Complete offset, or reversal of this interaction takes place 10–14 days after VPA discontinuation. Our data also confirms the observation that LTG oral clearance may be inhibited by very low concentrations of VPA. These data support the conversion algorithm suggested by the manufacturer, and provide guidance to the clinician. These data provide clinically useful information in developing a dosing algorithm for converting patients to LTG monotherapy.

Clinical and electrographic features of sunflower syndrome

BackgroundSunflower Syndrome describes reflex seizures – typically eyelid myoclonia with or without absence seizures – triggered when patients wave their hands in front of the sun. While valproate has been recognized as the best treatment for photosensitive epilepsy, many clinicians now initially treat with newer medications; the efficacy of these medications in Sunflower Syndrome has not been investigated. We reviewed all cases of Sunflower Syndrome seen at our institution over 15 years to describe the clinical course, electroencephalogram (EEG), and treatment response in these patients. MethodsSearch of the electronic medical record and EEG database, as well as survey of epilepsy providers at our institution, yielded 13 cases of Sunflower Syndrome between 2002 and 2017. We reviewed the records and EEG tracings. ResultsPatients were mostly young females, with an average age of onset of 5.5 years. Seven had intellectual, attentional or academic problems. Self-induced seizures were predominantly eyelid myoclonia ± absences and 6 subjects also had spontaneous seizures. EEG demonstrated a normal background with 3–4 Hz spike waves ± polyspike waves as well as a photoparoxysmal response. Based on both clinical and EEG response, valproate was the most effective treatment for reducing or eliminating seizures and improving the EEG; 9 patients tried valproate and 66% had significant improvement or resolution of seizures. None of the nine patients on levetiracetam or seven patients on lamotrigine monotherapy achieved seizure control, though three patients had improvement with polypharmacy. ConclusionsValproate monotherapy continues to be the most effective treatment for Sunflower Syndrome and should be considered early. For patients who cannot tolerate valproate, higher doses of lamotrigine or polypharmacy should be considered. Levetiracetam monotherapy, even at high doses, is unlikely to be effective.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third‐ line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment‐emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second‐ line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence‐based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first‐line treatments for acute mania. First‐line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first‐line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

Effect of antiepileptic drug comedication on lamotrigine concentrations.

AimTo estimate the effect size of concomitant antiepileptic therapy on the concentrations of lamotrigine, a drug often prescribed in combination with other antiepileptic drugs (AED), which can act as enzyme inducers or inhibitors.MethodsA total of 304 patients with epilepsy, aged 18-70 years, were divided into a lamotrigine monotherapy group and groups receiving lamotrigine with AEDs that act as enzyme inducers, enzyme inhibitors, or both. We compared lamotrigine monotherapy serum concentrations with those where lamotrigine was administered with a metabolic inhibitor valproate, metabolic inducers carbamazepine, oxcarbazepine, phenobarbital, phenytoin, or topiramate, and both an inducer and an inhibitor.ResultsComparison of trough lamotrigine monotherapy concentrations and lamotrigine polytherapy concentrations showed an almost similar median concentration in case of drug-inducers, and higher lamotrigine concentration in case of comedication with valproate as an inhibitor. A significant difference was confirmed after dose correction (P < 0.001). Significant positive correlations of lamotrigine trough serum concentrations with valproate were observed before and after the dose correction (r = 0.480, P < 0.001 and r = 0.561, P < 0.001, respectively). Positive correlations between the dose-corrected lamotrigine trough concentration and carbamazepine (r = 0.439; P < 0.001) or monohydroxy metabolite of oxcarbazepine (MHD) (r = 0.675; P < 0.001) were also significant.ConclusionHigher valproate levels resulted in higher inhibition potency and higher lamotrigine levels. Increased dose-corrected concentrations of inducers carbamazepine and MHD, after the process of induction was finished, did not lower lamotrigine concentrations. These findings can be of clinical significance for optimal AED dosing.

The clinical significance of the lamotrigine pharmacokinetic variability

To estimate pharmacokinetic variability of lamotrigine (LTG) and its clinical significance. One hundred patients, including 74 women, aged from 18 to 77 years (38.23±14.37 years), with focal epilepsy were examined. Monotherapy with LTG was administered to 54 patients, duotherapy to 46 patients (LTG and valproic acid combination to 27 patients, LTG and liver enzymes inducers to 19 patients). Patients underwent procedures of therapeutic drug monitoring (TDM). Minimal (Cssmin) and maximal (Cssmax) steady-state LTG plasma concentrations, and concentration-to-weight ratio (CDR) were calculated. In patients who used LTG in monotherapy, LTG Cssmin was 5.6±4.65 mg/l, Cssmax 7.59±5.54 mg/l. In the group that received LTG in combination with valproate, LTG Сssmin was 7.8 [5.4; 11.8] mg / l and Cssmax 11.4 [7.3; 15.3] mg/l. In the group that received LTG in combination with drug-inducers of glucuronidation, Cssmin was 2.5 [1.99; 4.32] mg/l, Cssmax 4.73 [2.91; 6.70] mg/l. Statistically significant differences in CDR parameter between groups with LTG monotherapy and duotherapy, both with inducer and with inhibitors, as well as between groups of duotherapy with inductors and with inhibitors were obtained. The results of the study indicate a pronounced pharmacokinetic variability of the LTG. Conducting TDM allows the establishment of individual therapeutic concentrations of LTG in blood plasma and setting a correction vector for antiepileptic therapy.

Effects of Antiepileptic Drugs on Language Abilities in Benign Epilepsy of Childhood with Centrotemporal Spikes.

Background and PurposeThis study is to assess the responsiveness of electroencephalography (EEG) abnormalities and their effects on language ability after initiating different types of antiepileptic therapy in children with newly diagnosed benign epilepsy of childhood with centrotemporal spikes (BECTS).MethodsThe records of patients newly diagnosed with BECTS (n=120; 69 males) were reviewed retrospectively. The patients were randomly treated with lamotrigine, oxcarbazepine, or topiramate monotherapy, and underwent at least two EEG and standardized language tests. Effects were compared using Pearson's chi-square tests and paired t-tests.ResultsThe recurrence rates for seizures in the lamotrigine, topiramate, and oxcarbazepine groups were 19.4%, 21.7%, and 11.4%, respectively, while complete or partial recovery (as indicated by EEG) occurred in 32%, 39%, and 16% of the patients. Patients in the lamotrigine group showed significant improvements in all parameters assessed by the Test of Language Problem Solving Abilities, except for ‘determining cause.’ Patients in the oxcarbazepine group also showed improvements, except for ‘making inferences’ (p<0.05). Most linguistic index scores were worse in the topiramate group except for Mean Length of Utterance in Words. Patients in the lamotrigine and oxcarbazepine groups showed significant improvements in the receptive language test (p<0.05). EEG improvements were not related to language ability.ConclusionsThe improvements in language and problem-solving performance in children with BECTS were greater for lamotrigine and oxcarbazepine than for topiramate. However, EEG remission did not imply that language function would be improved after the treatments.

Evaluate the effects of antiepileptic drugs on reproductive endocrine system in newly diagnosed female epileptic patients receiving either Valproate or Lamotrigine monotherapy: A prospective study

ObjectiveTo investigate the development of reproductive endocrine changes in Indian women with epilepsy initiating on either Valproate (VPA) or Lamotrigine (LTG) monotherapy. MethodsReproductive hormonal profiles, hirsutism, ovarian morphology by ultrasonography and menstrual cycle data in newly diagnosed women with epilepsy taking VPA (n=34) or LTG (n=32) monotherapy were compared. None of the women were receiving hormonal contraception. Patients gave details of seizure type and frequency, medical and drug history. Body weight and fasting insulin, glucose, testosterone, dihyroepiandrosterone sulfate (DHEAS), androstenedione, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH) were measured. Body mass index, free androgen index and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Longitudinal evaluations were done at 6th month and at 12th month. After 12th month some VPA-treated women were replaced with LTG and further followed-up twice in next six months. ResultsThe mean testosterone level was significant increased in VPA-treated women at 6th month (p=0.03), then at 12th month (p=0.01). More women in the valproate group than the lamotrigine group developed hirsutism (p=0.06), menstrual disturbances (p=0.02) and PCOS (p=0.001). Before valproate therapy, 32% of the patients were obese, this percentage rose to 47% after treatment (p=0.03). A significant positive correlation was existed between obesity (BMI >25) and the development of menstrual disturbances (p=0.006), serum testosterone levels (p=0.02) and PCOS (p=0.03). Insulin resistance (HOMA-IR >2.5) was significant correlated with menstrual disturbances (p=0.03) and serum testosterone levels (p=0.02). Substitution of VPA with LTG results in significant reduction in mean testosterone levels (p=0.005) and means body weight at 6th month (p=0.01). ConclusionLong-term valproate therapy in Indian women with epilepsy was associated with development of menstrual disturbances, alterations in reproductive hormonal function and increased the risk to developed PCOS.

Erratum to: Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A Systematic Review and Meta-Analysis.

Lamotrigine is used in pregnancy to control epilepsy and mood disorders. The reproductive safety of this widely used drug remains undefined and may represent a significant public health concern. We aimed to perform a systematic review and meta-analysis of existing knowledge related to malformation rates and maternal–neonatal outcomes after in utero exposure to monotherapy with lamotrigine. Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters) from database inception to July 2016; no language or date restrictions were applied. All publications of clinically relevant outcomes of pregnancies following in utero exposure to lamotrigine were included in this systematic review and meta-analysis. A total of 21 studies describing immediate pregnancy outcomes and rates of congenital malformations fulfilled the inclusion criteria. Compared with disease-matched controls (n = 1412, total number of patients) and healthy controls (n = 774,571, total number of patients), in utero exposure to lamotrigine monotherapy was found to be associated with significantly decreased rates of inborn defects (odds ratio [OR] 1.15; 95% confidence interval [CI] 0.62–2.16 and OR 1.25; 95% CI 0.89–1.74, respectively). Rates of miscarriages, stillbirths, preterm deliveries, and small for gestational age (SGA) neonates were not found to have been increased after in-utero exposure to LTG compared to the general population. Similarly, in utero exposure to lamotrigine monotherapy was not found to be associated with increased rates of inborn defects compared with in utero exposure to carbamazepine, and lamotrigine was found to be statistically significantly less teratogenic than valproic acid (n = 12,958 and 10,748; OR 0.84; 95% CI 0.68–1.03 and OR 0.32; 95% CI 0.26–0.39, respectively). No association was found between prenatal lamotrigine monotherapy and increased rates of birth defects and other explored variables related to adverse pregnancy outcomes.

Korean medication algorithm for bipolar disorder (KMAP-BP): Changes in treatment strategies for bipolar depression over 12 years

IntroductionMany guidelines for bipolar disorders have been introduced based on evidences. In contrast, KMAP-BP was developed by an expert-consensus.ObjectiveTo summarize the medication strategies for bipolar depression over four published KMAP-BP (2002, 2006, 2010, and 2014).MethodsThe questionnaire using a nine-point scale had covered some clinical situations with many treatment options about the appropriateness of treatment.ResultsFor mild-to-moderate depression, antidepressant (AD) + mood stabilizer (MS) in early editions and MS or lamotrigine monotherapy and AAP + (MS or lamotrigine) in later editions were preferred strategies. For severe nonpsychotic depression, MS + AD was the only first-line medication in early editions. In 2014, various medications [MS + AAP (atypical antipsychotic), AAP + lamotrigine, MS + AD] were preferred. Valproate and lithium has been rated as first-line MS in all editions. Lamotrigine were positively preferred later. Adjunctive AD was accepted as first-line strategy for severe depression in all editions. Preference of AAP also has been increased remarkably. Adjunctive AAP was not first-line treatment for mild-to-moderate depression in all editions, but was for nonpsychotic depression in 2010 and 2014 and for psychotic depression in all editions. Recommended AAPs have been changed over 12 years: olanzapine and risperidone in 2002 and quetiapine, aripiprazole, and olanzapine in 2014 were first-line AAP.ConclusionThere have been evident preference changes: increased for AAP and lamotrigine and decreased for AD. The high preferences for aripiprazole and lamotrigine in later editions were likely derived from favorable tolerability.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Evaluate the effects of long-term valproic acid treatment on metabolic profiles in newly diagnosed or untreated female epileptic patients: A prospective study

PurposeExcessive weight gain associated with sodium valproate (VPA) may predispose patients with epilepsy to other health problems such as insulin resistance. We prospectively evaluated the long-term impact of VPA monotherapy compared with lamotrigine (LTG) monotherapy on anthropometric and metabolic parameters in women with epilepsy. Our primary objective is to understand the underlying mechanism responsible for VPA-induced obesity. MethodsSixty-six female patients with newly diagnosed or untreated epilepsy were included in the study. Thirty-four patients with VPA and thirty-two patients with LTG were treated for a period of one year in our center. Anthropometric and clinical data were collected at 5 time points: before, at 6th week, 3rd month, 6th month, 9th month and 12th month (last visit). Biochemical and hormonal data were collected 2 time points: before and last visit. ResultsSubjects in the VPA group had significantly higher body weight than LTG-treated subjects (64.88±3.25 vs. 58.28±2.43, P<0.001). HOMA-IR level was significantly increased (2.76 vs. 1.35, P<0.05), and adiponectin levels were significantly lower in the VPA group (3.46 vs. 6.22, P<0.05). Triglycerides levels were significantly increased (118 vs. 96, P<0.05), and HDL-C levels were significantly lower in the VPA group. Both the VPA-treated group and the LTG-treated group showed no significant difference in term of total cholesterol, LDL-C, fasting blood glucose and serum leptin levels. ConclusionsBased on the findings of this study, we proposed that VPA induced hypoadiponectinemia which correlates significantly with insulin resistance. These two factors may be responsible for weight gain, possible by stimulating appetite. Valproic acid appears to be use cautionally in obese females with epilepsy.

Effects of lamotrigine on attention-deficit hyperactivity disorder in pediatric epilepsy patients.

PurposeThe purpose of this study was to investigate the effects of lamotrigine for the treatment of attention-deficit hyperactivity disorder (ADHD) symptoms in children with epilepsy.MethodsPediatric patients newly diagnosed with epilepsy (n=90 [61 boys and 29 girls]; mean age, 9.1±3.4 years) were enrolled. All patients were evaluated with the Korean ADHD rating scale (K-ARS)-IV before treatment with lamotrigine and after doses had been administered. The mean interval of ADHD testing was approximately 12.3 months. The initial dosage of lamotrigine was 1 mg/kg/day (maximum 25 mg/day for the first 2 weeks), and increased by 1 mg/kg every 2 weeks until titrated up to 7 mg/kg/day (or maximum 200 mg/day).ResultsThe mean ADHD test score of the 90 subjects was 17.0±1.8 at baseline. It was slightly reduced to 15.6±1.7 after lamotrigine monotherapy (P >0.01). Prior to treatment, a total of 31 patients (34.4%) met the diagnostic criteria for ADHD according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision, Of these 31 patients, 27 (87.1%) had significantly improved ADHD scores with lamotrigine monotherapy (28.0±1.6 reduced to 18.1±2.6, P<0.001). Among these 27 patients, 25 (92.6%) showed normalized electroencephalogram (EEG) and 26 (96.3%) achieved total freedom from seizures within 12 months of the initiation of lamotrigine monotherapy.ConclusionThe results from our study show that lamotrigine had a positive effect in pediatric epilepsy patients by reducing ADHD symptoms, preventing seizures, and normalizing EEG. However, further research is required to determine whether lamotrigine is efficacious against ADHD symptoms independent of its effects on epileptic seizures.

Long-term efficacy and safety of lamotrigine: Results from the open-label extension of the lamotrigine monotherapy study in adult Japanese patients with epilepsy

Long-term efficacy and safety of lamotrigine: Results from the open-label extension of the lamotrigine monotherapy study in adult Japanese patients with epilepsy

Safety of Long-term Use of Lamotrigine for the Treatment of Psychiatric Disorders.

Lamotrigine (LTG) is a drug commonly used to treat epilepsy and can also be used to manage mood disorders, such as bipolar disorder. One of the most dangerous adverse effects of LTG is skin rash, which can make early cessation necessary. Here, we examine the adverse effects associated with long-term use of LTG for the treatment of mood disorders. Data were obtained from the medical records of 101 psychiatric patients who were prescribed long-term treatment with LTG. Patients were retrospectively divided into those who discontinued treatment within 6 months and those who continued for longer, and the groups were compared for adverse effects. We also compared the incidence of adverse effects in high and low doses. Fifty-four patients continued LTG treatment for 6 months or longer; 47 discontinued within 6 months. A history of allergy was more prevalent among the patients who discontinued treatment early than in those who continued. Of the patients who continued treatment for 6 months or longer, only 2 later discontinued treatment because of adverse effects. Lamotrigine monotherapy showed no difference in the incidence of adverse effects for different doses of LTG (>200 mg = 4.8% vs >100 mg, ≤200 mg = 7.7%; P = 1, vs >50 mg, ≤100 mg = 0%; P = 1 vs ≤50 mg = 0%; P = 1). Clinicians must be mindful of the adverse effects occurring early during the titration phase. However, long-term use of LTG was very well tolerated, even at high maintenance doses.

Specific OCT1 and ABCG2 polymorphisms are associated with Lamotrigine concentrations in Chinese patients with epilepsy

PurposeThe pharmacokinetics of Lamotrigine (LTG) varies widely among patients with epilepsy. In this study, we are aiming to investigate the effects of OCT1, ABCG2, ABCC2 and HNF4α genetic polymorphisms on plasma LTG concentrations and therapeutic efficacy in Chinese patients with epilepsy. MethodsThe study cohort comprised 112 Han Chinese patients with epilepsy who were receiving LTG monotherapy. Blood samples were taken and LTG levels were measured. The polymorphisms of OCT1 rs2282143, rs628031, ABCG2 rs2231142, rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 were determined. The therapeutic efficacy of LTG at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. ResultsThere were significant associations between OCT1 rs628031, ABCG2 rs2231142 polymorphisms and normalized LTG concentrations in patients with epilepsy (P<0.05). On the other hand, polymorphisms of OCT1 rs2282143, ABCG2 rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 exhibited no correlation with LTG concentrations. Additionally, no significant association existed between all the studied genotypes and LTG treatment response. ConclusionsThese results suggested that the polymorphisms of OCT1 rs628031 and ABCG2 rs2231142 may affect LTG metabolism in Chinese patients with epilepsy. However, future studies are necessary to be investigated in a larger cohort of epileptic patients.