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Psychopharmacology Bulletin Mar 2021Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The... (Review)
Review
Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The condition centers around a delayed-type hypersensitivity reaction with a complex etiology stemming from a variety of causes. The number one cause is medication-related-common ones including sulfonamides, antiepileptics, allopurinol, and nonsteroidal anti-inflammatory drugs. Genetics also play a role as several human leukocyte antigen (HLA) genotypes within certain ethnic groups have been implicated in adverse reactions to specific drugs. HLAB*15:02 has been identified in the Chinese and others of Southeast Asian origin to increase susceptibility to lamotrigine and carbamazepine-induced SJS. Furthermore, patients of Japanese origin with HLAB*31:01 and Koreans with HLA-B*44:03 are also at increased risk of SJS after receiving the same two drugs. Of the antiepileptics, one most commonly associated with SJS is lamotrigine, a pre-synaptic voltage-gated sodium channel inhibitor. Lamotrigine is an antiepileptic drug of the phenyltriazine class that is indicated for the prevention of focal and generalized seizures in epileptic patients as well as monotherapy or adjunctive maintenance treatment for Bipolar disorder. The occurrence of SJS is not a rigid contraindication to lamotrigine reintroduction in the same patient. To facilitate this, manufacturers have developed a strict re-challenge dosing regimen to facilitate successful reintroduction of lamotrigine. In order to prevent the recurrence of SJS during a re-challenge, timing of re-dose and initial rash severity must be considered. Therefore, to prevent SJS recurrence, prime lamotrigine re-challenge patients are those with mild initial rash that has not occurred within the previous 4 weeks. The Federal Food and Drug Administration recommends the testing HLA subtypes for those associated with SJS prior to starting lamotrigine.
Topics: Anticonvulsants; Carbamazepine; HLA-B Antigens; Humans; Lamotrigine; Stevens-Johnson Syndrome; United States
PubMed: 34092825
DOI: No ID Found -
The Cochrane Database of Systematic... Sep 2021Bipolar disorder is a chronic mental disorder with repetitive mania/hypomania as well as depressive episodes, which eventually results in marked impairment in overall... (Review)
Review
BACKGROUND
Bipolar disorder is a chronic mental disorder with repetitive mania/hypomania as well as depressive episodes, which eventually results in marked impairment in overall functioning and health-related quality of life. A worldwide prevalence rate of 2.4% has been reported. The risk of suicide is higher in people with bipolar disorder than those with other mental disorders. Therefore, effective management of bipolar disorder in the maintenance period is warranted to minimize the risk of relapse or recurrence. Although lithium has been the standard treatment of bipolar disorder for many years, it is associated with adverse effects and teratogenicity. Lamotrigine is approved to be expected for prevention of recurrence for the maintenance treatment of bipolar disorder. In addition, lamotrigine is as effective as lithium. Therefore, we performed a systematic review to confirm the efficacy and safety of lamotrigine in the maintenance treatment of bipolar disorder.
OBJECTIVES
To assess the efficacy and tolerability of lamotrigine in the maintenance treatment of bipolar disorder.
SEARCH METHODS
We searched Ovid MEDLINE, Embase, PsycINFO, the Cochrane Common Mental Disorders Group's Specialized Register (CCMDCTR) and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 21 May 2021. We also searched international trial registries and contacted experts in the field.
SELECTION CRITERIA
We included randomized controlled trials enrolling adults with bipolar disorder who were treated with lamotrigine, placebo or lithium.
DATA COLLECTION AND ANALYSIS
Two reviews authors independently checked the eligibility of studies and extracted data using a standardized form. Data extracted included study characteristics, participant characteristics, intervention details, settings, and outcome measures in the term of efficacy and tolerability. Study information were then entered into RevMan web.
MAIN RESULTS
We included 11 studies with a total of 2314 participants in this review; 1146 were randomized to lamotrigine, 869 were randomized to placebo and, 299 to lithium. We rated all studies as having an unclear risk of bias in at least one domain of Cochrane's tool for assessing risk of bias, with the most commonly observed weakness being selection bias (random sequence generation and allocation concealment). We judged five studies to be at a high risk of detection bias (blinding of outcome assessment). These potential biases pose as major threat to the validity of the included studies in this review. Outcomes of efficacy showed a possible advantage of lamotrigine over placebo. The estimated risk ratio (RR) for recurrence of manic symptom at one year as measured by the Young Mania Rating Scale (YMRS) was 0.67, (95% confidence interval (CI) 0.51 to 0.87; 3 studies, 663 participants; low-certainty evidence) in favor of lamotrigine. The RR of clinical worsening with the need for additional psychotropic treatment (RR 0.82, 95% CI 0.70 to 0.98; 4 studies, 756 participants) based on moderate-certainty evidence. The possible benefits of lamotrigine were also seen for the outcome of treatment withdrawal due to any reason at 6-12 months after treatment (RR 0.88, 95% CI 0.78 to 0.99; 4 studies, 700 participants; moderate-certainty evidence). Regarding tolerability, our analyses showed that the incidence rates of adverse effects were similar between the lamotrigine group and the placebo group (short-term effect: RR 1.07, 95% CI 0.81 to 1.42; 5 studies, 1138 participants; very low-certainty evidence; long-term effect: RR 0.97, 95% CI 0.77 to 1.23; 4 studies, 756 participants; moderate-certainty evidence). In the comparison between lamotrigine and lithium, efficacy was similar between groups except for recurrence of mania episode at one year. Recurrence of manic symptoms was higher in the lamotrigine group than that of the lithium group (RR 2.13, 95% CI 1.32 to 3.44; 3 studies, 602 participants; moderate-certainty evidence). Analysis of adverse effects at 6-12 months showed that a lower proportion of participants experienced at least one adverse effect when treated with lamotrigine compared to lithium (RR 0.70, 95% CI 0.51 to 0.96; 4 studies, 691 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
Low- to moderate-certainty evidence collectively suggests that lamotrigine may be superior to placebo as a treatment modality for bipolar disorder. In comparison to lithium, people with bipolar disorder seem to tolerate lamotrigine better in the long run; however, the demonstrated efficacy in the maintenance of bipolar disorder was similar between the two groups.
Topics: Adult; Anticonvulsants; Bipolar Disorder; Humans; Lamotrigine; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 34523118
DOI: 10.1002/14651858.CD013575.pub2 -
Neurology India 2021Lamotrigine (LMT) is a phenyltriazine derivative that was originally described as an antiepileptic drug. (Review)
Review
BACKGROUND
Lamotrigine (LMT) is a phenyltriazine derivative that was originally described as an antiepileptic drug.
OBJECTIVE
This literature review aims to evaluate the clinical epidemiological profile, pathological mechanisms, and management of lamotrigine-associated movement disorders.
METHODS
Relevant reports in six databases were identified and assessed by two reviewers without language restriction. Reports that the individuals only developed tremor or ataxia after LMT use were not included.
RESULTS
In total 48 reports of 108 cases from 19 countries were assessed. The movement disorders associated with LMT found were 29 tics, 21 dyskinesias, 14 myoclonus, 13 parkinsonism, 10 dystonia, and 1 stuttering. The not clearly defined cases included 10 akathisia, 4 myoclonus, 4 cerebellar syndromes, 1 hypertonia, 1 dyskinesia, and an unknown number of dystonia cases. The mean reported age was 33.34 years (range: 1.574 years). The male was the predominant sex and the most common LMT indication was epilepsy. The mean LMT-dose at the movement disorder onset was 228 mg. The time from LMT start to the onset of movement disorder was within 6 months in 81%. The time from LMT withdrawal to complete recovery was within 1 month in 83%. The most common management was LMT withdrawal.
CONCLUSIONS
In the literature, the majority of the cases did not give a clear picture of the individual, and the times of movement disorder onset and recovery are not described. We believe that before withdrawal LMT, a dose adjustment based on the benefits and adverse events with careful evaluation case-by-case can be done.
Topics: Anticonvulsants; Ataxia; Epilepsy; Humans; Infant; Lamotrigine; Male; Movement Disorders
PubMed: 34979637
DOI: 10.4103/0028-3886.333440 -
Clinical Toxicology (Philadelphia, Pa.) Feb 2018Lamotrigine is a broad-spectrum anticonvulsant commonly used to treat seizure and bipolar mood disorders. Evidence from case series and retrospective studies indicate...
CONTEXT
Lamotrigine is a broad-spectrum anticonvulsant commonly used to treat seizure and bipolar mood disorders. Evidence from case series and retrospective studies indicate that lamotrigine overdose is usually benign. However, there are reported cases of cardiac arrest and mortality following lamotrigine overdose. We undertook a systematic review of the literature on lamotrigine overdoses to better understand the clinical severity, the relevance of serum concentrations, and therapeutic interventions for overdose.
OBJECTIVES
To characterize manifestations of acute lamotrigine overdose, determine if serum concentrations predict poisoning severity, and evaluate the effectiveness of overdose management interventions.
METHODS
We performed a literature search across eight databases, including Medline, EMBASE, and the Cochrane Library, from database inception to April 2014. Major bibliographic databases were updated on 31 May 2017. Articles were eligible if they described acute or acute on chronic lamotrigine overdose. At least one serum lamotrigine concentration had to be reported for inclusion. Reports on chronic poisoning, studies describing adverse effects of therapeutic use, and animal studies were excluded.
RESULTS
We retrieved 6238 records; 48 (51 cases) met the inclusion criteria. Cases primarily involved adults (70.6%). Potentially life-threatening symptoms of overdose included seizures (55%), Glasgow Coma Scale ≤8 (20%), hypotension (12%), and wide complex tachycardia (WCT) and cardiac arrest (6%). Among the 25 cases exposed to lamotrigine alone (13 adult; 12 pediatric), 2 adult fatalities occurred (4 g and 7.5 g ingested) and 8 pediatric cases experienced seizures (all children ≤3.5-years-old, 75% without an underlying seizure disorder, ≥ 525 mg ingested). The lowest seizure-associated serum concentration was 3.8 mg/L and 25.6 mg/L for pediatric and adult patients, respectively, suggesting children may be more susceptible to CNS toxicity. Cardiovascular toxicities occurred primarily in adult patients (threshold >25 mg/L). Overdose interventions included benzodiazepines (53%), propofol or barbiturates (14%), NaHCO (20%), lipid therapy (12%), and extracorporeal elimination (10%). NaHCO yielded no response in four of nine cases with conduction delays; however, two of the four cases subsequently responded with lipid therapy.
CONCLUSIONS
Most cases reporting lamotrigine exposures observed mild or no toxicity; however, large exposures were associated with severe CNS depression, seizures, cardiac conduction delays, wide complex tachycardia, and death. In adults with a serum concentration >25 mg/L, severe toxicity may occur. In patients ≤3.5 years of age, ingestions of ≥525 mg may produce severe CNS depression and seizures.
Topics: Adult; Anticonvulsants; Child; Drug Overdose; Humans; Lamotrigine; Renal Dialysis
PubMed: 28862044
DOI: 10.1080/15563650.2017.1370096 -
Cells Feb 2022Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been... (Review)
Review
BACKGROUND AND OBJECTIVES
Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been published, there is still not enough data on the effect of ketamine in combination with other medications. Particularly interesting is the combination of ketamine and lamotrigine, and its potential role in bipolar depression. The aim of this review was to identify animal and human studies in which ketamine and lamotrigine were used together in order to find out if there is scientific ground for combining ketamine and lamotrigine in the treatment of mood disorders. Directions for future studies are presented.
MATERIALS AND METHODS
PubMed and Web of Science were searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 methodology was applied.
RESULTS
Seventeen studies were included for review. Animal studies using models of depression suggested a synergistic effect of ketamine and lamotrigine in combination. Studies on healthy humans showed a reduction in ketamine-induced dissociative symptoms with lamotrigine pretreatment. In a study on patients with depression, ketamine and lamotrigine did not have a stronger antidepressant effect than ketamine alone, but in this study only one ketamine infusion was administered. One case series described the antidepressant and anti-suicidal effect of the combination in two bipolar patients. Available clinical studies on patients with mood disorders did not support the hypothesis that lamotrigine reduces ketamine-induced dissociative symptoms.
CONCLUSIONS
The results of the analyzed studies were not sufficient to answer any of the stated questions; however, they allowed us to delineate future research directions. The identified animal studies suggested a possible synergistic antidepressant effect of ketamine and lamotrigine. The available clinical studies were not conclusive. No controlled studies on large groups of bipolar patients with multiple ketamine infusions combined with lamotrigine treatment have been published so far. There is some evidence for the reduction of ketamine's side effects by lamotrigine, and there are reports suggesting that lamotrigine can reduce ketamine craving. More studies with follow-up are needed in order to investigate the ketamine-lamotrigine combination in bipolar patients.
Topics: Animals; Antidepressive Agents; Depression; Humans; Ketamine; Lamotrigine; Psychopharmacology
PubMed: 35203296
DOI: 10.3390/cells11040645 -
Lancet (London, England) Apr 2021Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as... (Randomized Controlled Trial)
Randomized Controlled Trial
The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial.
BACKGROUND
Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy.
METHODS
This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64).
FINDINGS
990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95-1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83-1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08-1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319-1·458) compared with 1·222 (1·110-1·283) for levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs.
INTERPRETATION
These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials.
FUNDING
National Institute for Health Research Health Technology Assessment programme.
Topics: Administration, Oral; Adolescent; Adult; Aged; Anticonvulsants; Child; Cost-Benefit Analysis; Epilepsies, Partial; Female; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Treatment Outcome; Young Adult; Zonisamide
PubMed: 33838757
DOI: 10.1016/S0140-6736(21)00247-6 -
American Journal of Therapeutics 2019Lamotrigine (LAM), an antiepileptic, with panoply of indications and uses in neurology, is FDA approved, in psychiatry, for bipolar prophylaxis. Apart from this... (Review)
Review
BACKGROUND
Lamotrigine (LAM), an antiepileptic, with panoply of indications and uses in neurology, is FDA approved, in psychiatry, for bipolar prophylaxis. Apart from this indication, trend of its use in psychiatry is on the rise addressing a multitude of disorders.
STUDY QUESTION
LAM remains one of only few psychotropic drugs with antiglutamate activity. This might render LAM a potential therapeutic option in treatment-resistant major psychiatric disorders. We reviewed LAM pharmacology and its diverse indications while examining the extant evidence.
METHODS
EMBASE, Ovid MEDLINE, PubMed, Scopus, Web of Science, and Cochrane Database of Systemic Reviews were searched for all relevant studies up to date of June 2016.
RESULTS
Sound evidence supports use of LAM for acute bipolar depression and prophylaxis, treatment-resistant schizophrenia, treatment-resistant obsessive-compulsive disorder, posttraumatic stress disorder, depersonalization disorder, and affective dysregulation and behavioral dyscontrol domains of borderline personality disorder. Less compelling evidence is present for use in behavioral and psychological symptoms of dementia and neuropsychiatric sequelae of traumatic brain injury. No evidence supports use in autism spectrum disorder or acute unipolar depression.
CONCLUSIONS
LAM is an important addition to the psychopharmacological armamentarium. Level of evidence supporting the use of LAM in off-label indications is highly variable, and hence, sound clinical judgment is necessary for its proper use and placement in real-life psychiatric practice and psychopharmacotherapy algorithms.
Topics: Anticonvulsants; Drug Utilization; Humans; Lamotrigine; Mental Disorders; Off-Label Use
PubMed: 30601211
DOI: 10.1097/MJT.0000000000000535 -
Critical Reviews in Analytical Chemistry 2022Lamotrigine owing to its excellent inhibitory property of neurotransmitter release especially glutamate is used in the treatment of epilepsy as a second-line... (Review)
Review
Lamotrigine owing to its excellent inhibitory property of neurotransmitter release especially glutamate is used in the treatment of epilepsy as a second-line antiepileptic drug. It differs from other antiepileptic drugs chemically and pharmacologically and is used as both monotherapy and adjunct therapy in the treatment of epilepsy. The present review focuses on two aspects (a) various analytical methods used in quantification of Lamotrigine in pharmaceutical formulations and (b) various analytical methods used to determine Lamotrigine in biological matrices. Here the various analytical methods are developed using different parameters and validation of employed methods is discussed. Estimated parameters like the linearity, LOD (Limit of detection) and LOQ (Limit of quantification) of validation are discussed for the individual method. The critical quality attributes like the wavelength of detection, mobile phase, columns, flow rate, retention time, and the sample preparation methods for the estimation of Lamotrigine by bioanalytical methods are also discussed.
Topics: Anticonvulsants; Drug Compounding; Epilepsy; Glutamates; Humans; Lamotrigine; Pharmaceutical Preparations; Triazines
PubMed: 33673783
DOI: 10.1080/10408347.2021.1886901 -
Tremor and Other Hyperkinetic Movements... 2023Movement disorders, including chorea, have been cited as a side effect of lamotrigine use. However, the association is controversial and clinical characteristics in such... (Review)
Review
BACKGROUND
Movement disorders, including chorea, have been cited as a side effect of lamotrigine use. However, the association is controversial and clinical characteristics in such cases are unclear. We sought to explore whether chorea may be associated with lamotrigine use.
METHODS
We performed a retrospective chart review of all patients diagnosed with chorea who had concurrent use of lamotrigine between 2000-2022. Demographic information and clinical characteristics were analyzed, including medical comorbidities and concurrent medication use. A literature search and review were conducted, with additional cases of lamotrigine-associated chorea analyzed.
RESULTS
Eight patients met the inclusion criteria for the retrospective review. In 7 patients, other causes of chorea were considered more likely. However, a 58-year-old woman with bipolar disorder on lamotrigine for mood stabilization had a clear association of chorea induced by lamotrigine. The patient was on multiple centrally active medications. Three additional cases of lamotrigine-associated chorea were identified through a literature review. In 2 of these cases, other centrally acting agents were used, and chorea was resolved with weaning lamotrigine.
DISCUSSION
Chorea is infrequently seen in the setting of lamotrigine use. In these rare cases, the presence of other centrally acting medications with lamotrigine may contribute to chorea.
HIGHLIGHTS
Lamotrigine use is associated with movement disorders, including chorea, but the characteristics are not clearly defined. From our retrospective review, one adult had clear temporal and dose-related association between chorea and lamotrigine. We analyzed this case in conjunction with a literature review of cases of chorea associated with lamotrigine.
Topics: Adult; Female; Humans; Middle Aged; Lamotrigine; Chorea; Retrospective Studies; Movement Disorders
PubMed: 36873912
DOI: 10.5334/tohm.751 -
International Journal of Molecular... Mar 2023The anti-epileptic drug lamotrigine (LTG) has been widely used to treat various neurological disorders, including epilepsy and bipolar disorder. However, its precise... (Review)
Review
The anti-epileptic drug lamotrigine (LTG) has been widely used to treat various neurological disorders, including epilepsy and bipolar disorder. However, its precise mechanism of action in the central nervous system (CNS) still needs to be determined. Recent studies have highlighted the involvement of LTG in modulating the activity of voltage-gated ion channels, particularly those related to the inhibition of neuronal excitability. Additionally, LTG has been found to have neuroprotective effects, potentially through the inhibition of glutamate release and the enhancement of GABAergic neurotransmission. LTG's unique mechanism of action compared to other anti-epileptic drugs has led to the investigation of its use in treating other CNS disorders, such as neuropathic pain, PTSD, and major depressive disorder. Furthermore, the drug has been combined with other anti-epileptic drugs and mood stabilizers, which may enhance its therapeutic effects. In conclusion, LTG's potential to modulate multiple neurotransmitters and ion channels in the CNS makes it a promising drug for treating various neurological disorders. As our understanding of its mechanism of action in the CNS continues to evolve, the potential for the drug to be used in new indications will also be explored.
Topics: Humans; Lamotrigine; Depressive Disorder, Major; Anticonvulsants; Epilepsy; Central Nervous System; Glutamic Acid; Ion Channels; Triazines
PubMed: 37047022
DOI: 10.3390/ijms24076050