Use Of Lamotrigine Research Articles

Estimating the effects of co-medications on plasma olanzapine concentrations by using a mixed model

The purpose of this study was to estimate the effect sizes of drug interactions on plasma olanzapine concentrations while adjusting for potentially confounding factors such as smoking. The estimation was performed by using a mixed model, data from a series of previously published studies of lamotrigine, oxcarbazepine, topiramate, and mirtazapine, and unpublished data from patients under clinical therapeutic drug monitoring (TDM). The total sample included 163 adult patients (age ≥ 18 years) who provided both steady-state plasma olanzapine concentrations and smoking information. They provided a total of 360 olanzapine concentrations (1 to 11 measures per patient). Smoking and concomitant carbamazepine or lamotrigine use were found to have significant effects on median plasma olanzapine concentrations. The effects of lamotrigine on plasma olanzapine concentrations were modified by smoking. After adjusting for olanzapine dose and carbamazepine intake, plasma olanzapine concentrations were 10% lower in non-smokers who were taking lamotrigine than in non-smokers who were not taking lamotrigine; olanzapine concentrations were 35% higher in smokers who were taking lamotrigine than in smokers who were not taking lamotrigine; olanzapine concentrations were 41% lower in smokers who were not taking lamotrigine than in non-smokers who were not taking lamotrigine; and olanzapine concentrations were 11% lower in smokers who were taking lamotrigine than in non-smokers who were taking lamotrigine. After adjusting for olanzapine dose and taking carbamazepine, the correction factor comparing smokers taking lamotrigine versus non-smokers who were not taking lamotrigine was 1.3. Gender, age, and concomitant use of mirtazapine, valproic acid, lamotrigine, topiramate, lorazepam, citalopram or oxcarbazepine did not have significant effects on olanzapine concentrations. The main limitation of this clinical design is the unavoidable substantial “noise” that characterizes (uncontrolled) clinical environments, which may make it difficult to detect the effects of some variables. Other limitations were the small sample size of some drug sub-samples and the lack of testing for plasma olanzapine metabolites.

Economic impact of generic substitution of lamotrigine: projected costs in the US using findings in a Canadian setting

ABSTRACTBackground: Generic substitution may not always save health care costs for antiepileptic drugs (AED).Objective: (1) To examine the economic impacts of generic substitution of lamotrigine in Canada; and (2) to convert observed Canadian costs to a United States (US) setting.Methods: Health claims from Québec's health plan (RAMQ) between 08/2002 and 07/2006 were analyzed. Patients with ≥ 1 epilepsy claim and treated with branded lamotrigine (Lamictal) before generic entry were selected. Health care costs ($/person-year) were compared during periods of branded and generic use of lamotrigine. Two cost-conversion methods were employed; one using purchasing power parities, US/Canada service use ratios, and exchange rate, and another employing Canadian health care utilization and US unit costs.Results: 671 patients were observed during 1650.9 and 291.2 person-years of branded and generic use of lamotrigine, respectively. The generic-use period was associated with an increase in overall costs (2006 constant Canadian dollars) relative to brand use (C$7902 vs. C$6419/person-year; cost ratio (CR) = 1.22; p = 0.05), despite the lower cost of generic lamotrigine. Non-lamotrigine costs were 33% higher in the generic period ( p = 0.013). Both conversion methods yielded increases in total projected health care costs excluding lamotrigine (2006 constant US dollars) during the generic period (Method 1: cost difference: US$1758/person-year, CR = 1.33, p = 0.01); Method 2: cost difference: US$2516, CR = 1.39, p = 0.004).Limitations: Study limitations pertain to treatment differences, indicators used for conversion and possible claim inaccuracies.Conclusion: Use of generic lamotrigine in Canada was significantly associated with increased overall medical costs compared to brand use. Projected overall US health care costs would likely increase as well.

Simultaneous Toxicities in a Child on Multiple Anticonvulsants

It is rare to develop simultaneous toxicities while on anticonvulsants. This article presents a 3(1/2)-year-old child on valproic acid, lamotrigine, and phenytoin who developed simultaneous hepatotoxicity and bone marrow toxicity during a parainfluenza virus type 3 infection. These toxicities resolved after the cessation of anticonvulsants, and her seizures were managed acutely with scheduled lorazepam. This article discusses the possibility that simultaneous use of valproic acid, lamotrigine, and phenytoin could give this combination of toxicities and that concurrent viral infection may increase this risk.

Lamotrigine in motor and mood symptoms of Huntington's disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by midlife onset, progressive course and a combination of motor, cognitive and psychiatric symptoms. Since dysregulation of the glutamate/calcium signalling pathway is beginning to emerge as a potential cause of neuron degeneration, antagonists of glutamate pathways such as lamotrigine, may have beneficial value for treatment of HD. We describe the use of lamotrigine in the treatment of an HD patient with motor abnormality (choreoathetoidic movements) complicated by psychiatric abnormalities (depression, severe mood swing and recurrent high risk of suicidal attempts). The patient's depression, severe mood swing and choreoathetoidic movements significantly improved with 300 mg/day of lamotrigine. Experience from our patient suggests that lamotrigine might be effective in treating HD patients with motor and mood symptoms. Further controlled studies are warranted to confirm its efficacy in patients of this type.

Depersonalization disorder: pharmacological approaches

Depersonalization disorder (DPD) is a chronic and distressing condition with a prevalence in the general population between 0.8 and 2%. Several neurobiological studies in the last decade have shown that patients have suppressed limbic activation to emotional stimuli. Such findings are in line with a model which suggests that the condition is generated by an anxiety-triggered, ’hard-wired’ inhibitory response to threat. Such a mechanism would ensure the preservation of adaptive behavior, during situations normally associated with overwhelming and potentially disorganizing anxiety. In DPD, such a response would become chronic and dysfunctional. Depersonalization remains a condition for which no definitive treatment exists, and for which conventional medications, such as antidepressants or antipsychotics, have been found to be of little value. Fortunately, a few promising lines of pharmacological treatment have emerged in recent years, although more rigorous studies are needed. For example, a number of studies suggest that opioid receptor antagonists such as naltrexone and naloxone are useful in at least a subgroup of patients. In spite of initial expectations, the use of lamotrigine as a sole medication has not been found useful. However, open-label trials suggest that its use as an add-on treatment with selective serotonin reuptake inhibitors (SSRIs) is beneficial in a substantial number of patients. Similarly, the use of clonazepam, particularly in conjunction with SSRI antidepressants, appears to be beneficial in patients with high levels of background anxiety. In line with the stress-related model of depersonalization, those neurotransmitter systems of relevance to depersonalization are known to play important inhibitory roles in the regulation of the stress response.

Late side-effects of valproate and lamotrigine

Lamotrigine (LTG) is a generally well-tolerated antiepileptic drug with broad-spectrum efficacy in several forms of partial and generalized epilepsy. Adverse effects of lamotrigine are usually associated with introduction and titration. This risk increases in children and in the co-medication with valproate. Herein, we report four patients with late adverse-effects, under the co-medication valproate and LTG, not related to drug introduction or titration. This study demonstrates that late side-effects without apparent etiology in children, adolescents and adults in chronic use of LTG, especially when associated to VPA, led to a diagnostic investigation, sometimes invasive. It must be emphasized that, due to the excellent seizure control, the authors opted for drug decrease instead of drug withdrawal, as previously done. Studies on late adverse effects are scarce, but physicians must be aware of these risks.

Lamotrigine as Add-On Therapy in Schizophrenia

: Lamotrigine previously was found to attenuate ketamine-induced behavioral changes and, in 2 placebo-controlled trials, to improve psychosis when added to antipsychotic medication. We sought to evaluate the potential role of lamotrigine augmentation in schizophrenia patients resistant to atypical antipsychotic medication. : Two multicenter, randomized, double-blind, 12-week, parallel-group trials were conducted to compare flexibly dosed lamotrigine (100-400 mg/d) with placebo as add-on treatment in schizophrenia patients with stable, residual psychotic symptoms. The primary end point was changed in Positive and Negative Syndrome Scale total score at week 12. : Two hundred seventeen patients were enrolled in study 1 and 212 in study 2; completion rates in the intent-to-treat samples were 71% and 74%, respectively, and did not differ between treatment groups. Overall, mean Positive and Negative Syndrome Scale total scores improved in both studies and did not differ between treatment groups. In study 1, the Scale for Assessment of Negative Symptoms total score and Clinical Global Impression improved more with placebo than with lamotrigine; in study 2, the cognitive composite score improved more with lamotrigine than with placebo. : Results from these 2 studies do not support the use of lamotrigine as an adjunct to atypical antipsychotics in patients with refractory psychosis. It is unclear why positive results from previous lamotrigine trials were not replicated. The positive effect of lamotrigine on cognition in one trial, while of uncertain significance, may merit further study.

Lamotrigine in pregnancy

To characterize the magnitude and course of alterations in total and free lamotrigine (LTG) clearance (Cl) during pregnancy and the postpartum period, to assess the impact of therapeutic drug monitoring (TDM) on seizure frequency, to determine the ratio to individual target LTG concentration that is associated with increased seizure risk, and to evaluate maternal postpartum toxicity. A cohort of women were enrolled before conception or during pregnancy in this prospective, observational study. Visits occurred every 1 to 3 months with review of seizure and medication diaries, examination, and blood sampling. Total and free LTG Cls were calculated. Individualized target concentrations were used for TDM. The ratio to target concentration (RTC) was compared between patients with and without increased seizures. A receiver operating characteristic curve determined the threshold RTC that best predicts increased seizure frequency. Analysis of 305 samples in 53 pregnancies demonstrated increased total and free LTG Cl in all trimesters above nonpregnant baseline (p < 0.001), with peak increases of 94% and 89% in the third trimester. Free LTG Cl was higher in white compared with black women (p < 0.05). Increased seizure frequency (n = 36 women with epilepsy) in the second trimester was associated with a lower RTC (p < 0.001), and RTC < 0.65 was a significant predictor of seizure worsening. An empiric postpartum taper reduced the likelihood of maternal LTG toxicity (p < 0.05) (n = 27). Newborn outcomes were similar to the general population (n = 52). These novel data contribute to a rational treatment plan and dosing paradigm for lamotrigine use during pregnancy, parturition, and the postpartum period.

A randomized, double-blind, placebo-controlled, two-period, crossover, pilot trial of lamotrigine in patients with central pain due to multiple sclerosis

Background: Approximately 30% of patients with multiple sclerosis (MS) have central pain (CP). The anticonvulsant lamotrigine has been shown to be efficacious in some types of CP, but its efficacy in MS-related CP has not been confirmed. Objective: The aim of this pilot trial was to provide preliminary data for a planned larger trial. Methods: A randomized, double-blind, placebo-controlled, 2-period, crossover pilot study was conducted in a sample of patients aged ≥18 years with CP due to MS. The 2 treatment periods began with an 8-week, double-blind titration period, during which the number of pills of study drug was increased until either total pain relief was achieved, 1 or more unmanageable adverse events were reported, or a maximum of 16 pills (400 mg of lamotrigine) were used daily. A 3-week maintenance period at the final prescribed amount was followed by a 2-week tapering period; there was a 2-week washout between the 2 treatment periods, after which patients were administered the alternate drug. Outcomes before, during, and after each study period were assessed using validated measures of pain and quality of life (the Brief Pain Inventory [BH], the Neuropathic Pain Scale [NPS], and the 54-item MS Quality of Life [MSQOL-54] questionnaire). Throughout the trial, patients completed a daily diary consisting of questions from the BPI-Short Form, as well as questions about the use of other analgesic drugs, changes in health, and the occurrence of adverse events. The BPI and NPS were completed weekly during telephone calls with the research coordinator, and the MSQOL-54 was administered during clinic visits (ie, visits at screening, baseline, end of period 1, and termination). The primary outcome measure was the mean pain intensity score during the final maintenance week of each of the 2 study periods. Results: A total of 12 patients were enrolled and completed at least the first period of the study. Ten patients were women. The mean (SD) age was 49.3 (11.7) years, and the mean (SD) weight was 76.5 (19.9) kg. The analysis revealed no significant differences between the lamotrigine and placebo periods in any of the study outcomes related to pain or quality of life. Regarding adverse events, 1 patient developed a moderate rash during the study, but the physician attributed this lesion to herpes zoster; this patient completed the study. While other adverse events were mild, 2 patients were withdrawn from the study after experiencing adverse events during the first study period; 1 had been receiving lamotrigine and the other placebo. Conclusion: The results from this pilot trial did not support either the use of lamotrigine in patients with MS-related CP or the need for a larger trial.

Concomitant use of lamotrigine and aripiprazole increases risk of Stevens–Johnson syndrome?

Stevens-Johnson syndrome is a severe and potentially life-threatening cutaneous reaction associated with lamotrigine. The incidence of developing Stevens-Johnson syndrome during lamotrigine therapy is low. On the basis of the glutamate and dopamine neuron dysregulation hypothesis in schizophrenia, we propose new strategies for the treatment of schizophrenic patients using a glutamate system stabilizer lamotrigine as an adjunctive treatment for the poor responders of a dopamine system stabilizer, aripiprazole. The finding of Stevens-Johnson syndrome in two cases out of three treated with lamotrigine plus aripiprazole, however, has a much higher index of suspicion and it is correct to warn of its possible raised risk. As lamotrigine is currently licensed for the prophylactic treatment of bipolar depression, many of these patients have psychotic features where it would be considered reasonable to add an antimanic atypical antipsychotic such as aripriprazole. The two case reports raised the question about the possible increased risk of Stevens-Johnson syndrome with the combination therapy.

Central Post-Stroke Pain Syndrome

Dr. Gevirtz is Clinical Associate Professor, Department of Anesthesiology, Louisiana State University-New Orleans, LA, and Medical Director, Somnia Pain Management, 627 West Street, Harrison, NY 10528; E-mail: [email protected]. Dr. Gevirtz has disclosed that he has no significant relationships with or financial interests in any commercial organizations pertaining to this educational activity. He also has disclosed that the use of ketamine (Ketalar, Parke-Davis), amitriptyline (Elavil, AstraZeneca), lamotrigine (Lamictal, GlaxoSmithKline), propofol (Diprivan, AstraZeneca), and lidocaine (Xylocaine, AstraZeneca) for central post-stroke pain as discussed in this article has not been approved by the U.S. Food and Drug Administration. Lippincott CME Institute, Inc., has identified and resolved all faculty conflicts of interest regarding this educational activity.

Under‐recruitment of patients for clinical trials: an illustrative example of a failed study

Under‐recruitment of patients for clinical trials: an illustrative example of a failed study

Lamotrigine-induced Stevens-Johnson syndrome

A case of lamotrigine-induced Stevens-Johnson syndrome (SJS) is reported. A 29-year-old woman with a medical history of schizoaffective disorder arrived at the emergency department with a severe generalized skin reaction. Three to four days prior she had noticed bumps on her lips that had spread to her oral mucosa. She had also developed a diffuse, erythematous, pruritic full-body rash involving the palms of her hands and the soles of her feet and began to feel feverish. Her medications at admission included aripiprazole 30 mg p.o. daily, escitalopram 10 mg p.o. daily, and lamotrigine 75 mg p.o. daily. Lamotrigine was the only new medication, initiated four weeks before this admission. The dermatology service confirmed the diagnosis of SJS using punch biopsy. Lamotrigine was suspected to be the culprit and was discontinued immediately. The patient was given oral prednisone 40 mg and intravenous fluids. Hydroxyzine was given for pruritus, and petroleum jelly and viscous lidocaine were applied to her lips. On hospital day 2, her symptoms and dermatological manifestations improved, but she continued to complain about irritation and slight pain of the mouth. She then received a mouthwash consisting of diphenhydramine, viscous lidocaine, and sodium bicarbonate. On hospital day 3, the patient had improved substantially and was discharged home. Reports of these dermatological reactions in patients receiving lamotrigine for the treatment of bipolar disorder are limited. Dosing, prompt recognition, and patient education are crucial for preventing morbidity and mortality associated with the development of serious cutaneous reactions. SJS was associated with lamotrigine use, despite appropriate dosing and dosage adjustment.

Bipolar Disorder Clinical Synthesis: Where Does the Evidence Lead?

Bipolar disorder is a common condition diagnosed by the occurrence of pathological mood elevation but most often dominated by dysphoria states. Over the past 10 years, understanding of bipolar disorder and the number of evidence-based treatments have increased dramatically. This article offers strategies for improving diagnostic confidence and simple benchmarks that facilitate integrating principles of evidence-based medicine into the management of patients with bipolar disorder. Simple systematic assessment techniques such as focusing the evaluation to assess the most extreme episode of mood elevation and longitudinal factors such as age of onset and course of illness can avoid errors of omission and raise diagnostic confidence. An iterative measurement-based treatment model that aims to bring patients and their supports into the collaborative care process for progressively better outcomes is recommended.

Stevens-Johnson Syndrome Due to Concomitant Use of Lamotrigine and Valproic Acid

Stevens-Johnson syndrome (SJS) is a rare but life-threatening acute mucocutaneous hypersensitivity reaction, usually related to drugs. Severe cutaneous adverse effects such as SJS and toxic epidermal necrolysis can arise during treatment with antiepileptic drugs (AEDs). A 23-year-old female patient with idiopathic epilepsy was referred to the emergency service with fever, oral and genital mucosal lesions, generalized rash, and weakness. She had been taking carbamazepine, valproic acid, and lamotrigine until 1 week prior to referral. Following consultations with a range of clinicians, the patient was diagnosed with SJS related to lamotrigine on the basis of her history and physical findings, and on consideration of current consensus definitions of this condition. The patient was followed up and treated in the emergency intensive care unit with intravenous fluids, antibacterial therapy, and methylprednisolone. After 18 days, the patient was considered to have made a sufficient recovery and was discharged. Patients who undergo therapy with AEDs, particularly new users of these agents, should be informed of and monitored for possible systemic and cutaneous adverse effects of AEDs. Polytherapy should be avoided for as long as possible as this increases the frequency of adverse effects, and treatment should be discontinued if any rash appears.

Treatment of inhalant dependence with lamotrigine

The sites of action of inhalant drugs are not completely known but recent studies suggest that ion channels that regulate neuronal excitability may be particularly sensitive. Lamotrigine, a newer anticonvulsant, has a modulating effect on excitatory amino acid–glutamate. We describe the use of lamotrigine in the treatment of a patient with inhalant dependence. A 21-year-old male with no history of other substance problems complained of problems with exacerbating use of inhalants for 4 years. He received a course of individual and behavior psychotherapy for 2 months. However, the psychotherapy was not effective. He then was treated with lamotrigine 100 mg per day. He has been on the dose of this medication for more than 6 months and stopped the use of inhalants. Experience with our patient suggests that lamotrigine might be effective in treating inhalant dependence. Further controlled studies are required to confirm its efficacy in patients of this type.

First-Trimester Lamotrigine Use Tied to Defects

First-Trimester Lamotrigine Use Tied to Defects

Lamotrigine for schizophrenia

Treating the 20-30% of people with schizophrenia whose symptoms are resistant to treatment can be problematic. Adding lamotrigine to ongoing antipsychotic treatment has shown to be of benefit in preliminary studies. To evaluate the effects of adjuvant lamotrigine for people with schizophrenia and schizophrenia-like psychoses. We searched the Cochrane Schizophrenia Group's Register (February 2006) and inspected references of all identified studies for further trials. We contacted relevant authors of trials for additional information. We included all clinical randomised trials comparing lamotrigine with placebo or other antipsychotic augmentation strategies. We extracted data independently. For homogenous dichotomous data we calculated random effects relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We found five relevant trials (total n=537), but no usable data on service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment or economic outcomes. Overall, reporting of data was poor. Those data we were able to use suggested that equal proportions of people allocated lamotrigine or placebo had no global response (n=208, 1 RCT, RR 1.06 CI 0.73 to 1.54). There was no significant difference between groups in the proportions of people whose mental state did not improve (n=297, 3 RCT, RR 1.26 CI 0.81 to 1.97). There was, however, a significant reduction in the PANSS total scores (n=67, 2 RCT, WMD -16.88 CI -8.57 to -25.18, p=0.0001), positive symptom sub-scale scores (n=65, 2 RCTs, WMD -5.10 CI -8.86 to -1.34) and negative symptom sub-scale scores (n=67, 2 RCTs, WMD -5.25, CI -7.07 to -3.43). Most cognitive measures showed no differences (n=329, 2 RCTs, RR not attaining BACS composite score of 0.5 1.10 CI 0.59 to 2.04). The proportion of participants leaving studies was about 25% at 12 weeks (n=537, 5 RCTs, RR 0.96 CI 0.71 to 1.29). The lamotrigine group did experience the outcome of any adverse effects significantly more frequent than people allocated placebo (n=429, 2 RCTs, RR 1.19 CI 1.02 to 1.38, NNH 10 CI 5 to 90). Among the many effects listed, only nausea was found to be significantly more (9%) in the lamotrigine group compared with placebo (n=465, 3 RCTs, RR 2.26 CI 1.05 to 4.88). Evidence for use of lamotrigine as an adjuvant for people with schizophrenia is not robust and large well-designed, conducted and reported real-world randomised trials are needed to determine its place in everyday clinical practice.

First-Trimester Lamotrigine Use May Cause Oral Clefts

First-Trimester Lamotrigine Use May Cause Oral Clefts

Long-Term Lamotrigine Plus Lithium for Bipolar Disorder: One Year Outcome

To obtain pilot data in an observational setting on the use of lamotrigine plus lithium in the long-term treatment of patients with bipolar disorder, 87% of whom had failed to respond to at least one previous mood stabilizer. Charts of 21 patients (11 females, 10 males, mean age 43.2 years) treated with the combination of lithium and lamotrigine were reviewed retrospectively for treatment response using the Clinical Global Impression-Bipolar Disorder-Improvement scale, divided into benefit for acute depressive symptoms, acute manic symptoms, and overall illness (including prophylaxis of mood episodes). Of the 21 patients, 76% were diagnosed with bipolar I disorder, and depressive symptoms were the most common acute indication for treatment (52%). Mean doses of lithium and lamotrigine were 963 mg/day and 179 mg/day, respectively, used for a mean of 55.7 weeks. Acute antidepressant benefit was observed in 48% of patients, acute anti-manic benefit in 14%, and overall prophylactic benefit in 29%. Side effects were observed in 38%, with cognitive problems most common (29%). 48% discontinued combination therapy, mainly due to lack of efficacy (19%) or activation of manic-like symptoms (19%). Among a group of largely treatment-resistant bipolar patients, the combination of lithium and lamotrigine appeared effective for acute depressive symptoms in about half of the patients, but acute anti-manic and long-term prophylactic efficacy appeared less robust.