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BMJ Case Reports Jan 2021Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder of excessive immune activation. It is mostly seen in the paediatric population and is...
Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder of excessive immune activation. It is mostly seen in the paediatric population and is rarely observed in adults. HLH can be inherited or acquired and is commonly triggered by activation of the immune system by an underlying viral infection or in immune system deficiency such as malignancy or underlying rheumatological disease. HLH is a difficult entity to diagnose due to the rarity of this disorder, variable clinical presentation and non-specific clinical and laboratory findings. HLH carries a high mortality if left untreated, and therefore prompt diagnosis and initiation of immunosuppressive, immunomodulatory and cytostatic medications are critical to improve survival in affected patients. Here, we present a case of lamotrigine-associated HLH. To our knowledge, only eight other cases of lamotrigine-associated HLH have been reported in adult patients.
Topics: Adult; Anticonvulsants; Biopsy; Bone Marrow; Dexamethasone; Diagnosis, Differential; Etoposide; Humans; Lamotrigine; Lymphohistiocytosis, Hemophagocytic; Male; Seizures
PubMed: 33408106
DOI: 10.1136/bcr-2020-238183 -
Epilepsia Sep 2022The US Food and Drug Administration recently issued a warning against the use of the antiseizure medication lamotrigine in people at risk of cardiac rhythm and...
OBJECTIVE
The US Food and Drug Administration recently issued a warning against the use of the antiseizure medication lamotrigine in people at risk of cardiac rhythm and conduction abnormalities. This study assessed the risk of cardiac morbidity and mortality in new users of lamotrigine.
METHODS
In a Danish population-based cohort study, we followed cohort members aged ≥15 years for the first 2 years after they initiated lamotrigine therapy. The main outcomes were cardiac conduction disorders in people without pre-existing cardiac morbidity and all-cause mortality in people with pre-existing cardiac morbidity. Cox proportional hazards models provided hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for comparison of the risk in current versus past users of lamotrigine.
RESULTS
There were 91 949 (36 618 males [39.8%]) new users of lamotrigine (median age = 45.7 years, interquartile range = 32.0-60.2 years). Among users without pre-existing cardiac disease (n = 86 769), 194 (.23%) developed a cardiac conduction disorder. Comparison of the risk in current and past lamotrigine treatment periods yielded an adjusted HR of new onset cardiac conduction disorder of 1.03 (95% CI = .76-1.40). Among users with pre-existing cardiac disease (n = 5180), 1150 (22.2%) died. Comparison of the risk in current and past lamotrigine treatment periods yielded an adjusted HR for all cause-mortality of 1.05 (95% CI = .93-1.19).
SIGNIFICANCE
In this large population-based study, lamotrigine use was associated neither with a risk of cardiac conduction disorders in people without pre-existing cardiac morbidity nor with all-cause mortality in people with pre-existing cardiac morbidity.
Topics: Adult; Anticonvulsants; Cohort Studies; Heart Diseases; Humans; Lamotrigine; Male; Middle Aged; Morbidity; Triazines
PubMed: 35735211
DOI: 10.1111/epi.17339 -
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 -
JAMA Psychiatry May 2022Osteoporosis, a systemic skeletal disorder associated with substantial morbidity and mortality, may be particularly common among individuals with bipolar disorder....
IMPORTANCE
Osteoporosis, a systemic skeletal disorder associated with substantial morbidity and mortality, may be particularly common among individuals with bipolar disorder. Lithium, a first-line mood-stabilizing treatment for bipolar disorder, may have bone-protecting properties.
OBJECTIVE
To evaluate if treatment with lithium is associated with a decrease in risk of osteoporosis among patients with bipolar disorder.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included 22 912 adults from the Danish Psychiatric Central Research Register who received an initial diagnosis of bipolar disorder in the period from January 1, 1996, to January 1, 2019. For each patient with bipolar disorder, 5 age- and sex-matched individuals were randomly selected from the general population as reference individuals. Individuals with bipolar disorder prior to January 1, 1996, those with a diagnosis of schizophrenia or schizoaffective disorder prior to being diagnosed with bipolar disorder, and those with osteoporosis prior to the index date were excluded. Of the 114 560 reference individuals included, 300 were diagnosed with bipolar disorder during follow-up and were censored from the reference group from the date of diagnosis forward. For patients with bipolar disorder, treatment periods with lithium, antipsychotics, valproate, and lamotrigine were identified. Analyses were performed between January 2021 and January 2022.
EXPOSURES
Bipolar disorder and treatment with lithium, antipsychotics, valproate, and lamotrigine.
MAIN OUTCOMES AND MEASURES
The primary outcome was osteoporosis, identified via hospital diagnoses and prescribed medications. First, incidence of osteoporosis was compared between patients with bipolar disorder and reference individuals (earliest start of follow-up at age 40 years) using Cox regression. Subsequently, incidence of osteoporosis for patients receiving treatment with lithium, antipsychotics, valproate, and lamotrigine, respectively, was compared with that of patients who were not treated with these medications.
RESULTS
A total of 22 912 patients with bipolar disorder (median [IQR] age, 50.4 [41.2-61.0] years; 12 967 [56.6%] women) and 114 560 reference individuals (median [IQR] age, 50.4 [41.2-61.0] years; 64 835 [56.6%] women) were followed up for 1 213 695 person-years (median [IQR], 7.68 [3.72-13.24] years). The incidence of osteoporosis per 1000 person-years was 8.70 (95% CI, 8.28-9.14) among patients and 7.90 (95% CI, 7.73-8.07) among reference individuals, resulting in a hazard rate ratio (HRR) of 1.14 (95% CI, 1.08-1.20). Among patients with bipolar disorder, 8750 (38.2%) received lithium, 16 864 (73.6%) received an antipsychotic, 3853 (16.8%) received valproate, and 7588 (33.1%) received lamotrigine (not mutually exclusive). Patients with bipolar disorder treated with lithium had a decrease in risk of osteoporosis (HRR, 0.62; 95% CI, 0.53-0.72) compared with patients not receiving lithium. Treatment with antipsychotics, valproate, and lamotrigine was not associated with reduced risk of osteoporosis.
CONCLUSIONS AND RELEVANCE
In this study, bipolar disorder was associated with an increase in risk of osteoporosis, and lithium treatment was associated with a decrease in risk of osteoporosis. These findings suggest that bone health should be a priority in the clinical management of bipolar disorder and that the potential bone-protective properties of lithium should be subjected to further study, both in the context of bipolar disorder and in osteoporosis.
Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Lamotrigine; Lithium; Lithium Compounds; Male; Middle Aged; Osteoporosis; Retrospective Studies; Valproic Acid
PubMed: 35353126
DOI: 10.1001/jamapsychiatry.2022.0337 -
Neurological Sciences : Official... Mar 2022Epilepsy treatment during pregnancy is still challenging. The study is aimed at comparing the efficacy and safety of carbamazepine (CBZ), lamotrigine (LTG) and...
OBJECTIVE
Epilepsy treatment during pregnancy is still challenging. The study is aimed at comparing the efficacy and safety of carbamazepine (CBZ), lamotrigine (LTG) and levetiracetam (LEV) monotherapies during pregnancy in women with focal (FE) or generalized (GE) epilepsy.
METHODS
A multicentre retrospective study was conducted to evaluate seizures frequency and seizure freedom (SF) rate during 3 months before pregnancy, each trimester of gestation and post-partum period in women on monotherapy with CBZ, LTG and LEV.
RESULTS
Fifty-seven pregnancies (45 FE, 12 GE) on monotherapy (29 CBZ, 11 LTG, 17 LEV) were included. A significant reduction of seizure frequency was found in the first trimester of pregnancy as compared with that one before pregnancy (p = 0.004), more evident in GE (p = 0.003) and in LEV group (p = 0.004). The SF rate significantly increased in the first trimester in comparison to that one before pregnancy and persisted in the post-partum period in the whole sample (p < 0.001) and in women on LEV (p = 0.004). Besides, 88.57% of SF women before pregnancy remained unchanged during gestation and the post-partum period. One major heart malformation in CBZ and no major malformations in LTG and LEV groups were found.
CONCLUSIONS
A better clinical outcome during pregnancy emerged since the first trimester in comparison to the before-pregnancy period, mostly evident in women with GE and LEV therapy, reinforcing the hypothesis of a protective role of pregnancy versus seizures. SF before pregnancy represents a significant predictive factor of good clinical outcome during gestation and the post-partum period. Compared to CBZ, LTG and LEV showed a better safety profile.
Topics: Anticonvulsants; Carbamazepine; Female; Humans; Lamotrigine; Levetiracetam; Pregnancy; Retrospective Studies; Triazines
PubMed: 34468899
DOI: 10.1007/s10072-021-05542-2 -
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 -
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 -
The Cochrane Database of Systematic... Feb 2011This is an update of the original Cochrane review published in Issue 2, 2007. Some antiepileptic medicines have a place in the treatment of neuropathic pain (pain due to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the original Cochrane review published in Issue 2, 2007. Some antiepileptic medicines have a place in the treatment of neuropathic pain (pain due to nerve damage). This updated review adds five new additional studies looking at evidence for Lamotrigine as an effective treatment for acute and chronic pain.
OBJECTIVES
To assess analgesic efficacy and adverse effects of the antiepileptic drug lamotrigine in acute and chronic pain.
SEARCH STRATEGY
Randomised controlled trials (RCTs) of lamotrigine in acute, and chronic pain (including cancer pain) were identified from MEDLINE, EMBASE and CENTRAL up to January 2011. Additional studies were sought from the reference list of the retrieved papers.
SELECTION CRITERIA
RCTs investigating the use of lamotrigine (any dose, by any route, and for any study duration) for the treatment of acute or chronic pain. Assessment of pain intensity or pain relief, or both, using validated scales. Participants were adults aged 18 and over. Only full journal publication articles were included.
DATA COLLECTION AND ANALYSIS
Dichotomous data (ideally for the outcome of at least 50% pain relief) were used to calculate relative risk with 95% confidence intervals. Meta-analysis was undertaken using a fixed-effect model. Numbers needed to treat to benefit (NNTs) were calculated as the reciprocal of the absolute risk reduction. For unwanted effects, the NNT becomes the number needed to harm (NNH) and was calculated.
MAIN RESULTS
Twelve included studies in 11 publications (1511 participants), all with chronic neuropathic pain: central post stroke pain (1), chemotherapy induced neuropathic pain (1), diabetic neuropathy (4), HIV related neuropathy (2), mixed neuropathic pain (2), spinal cord injury related pain (1), and trigeminal neuralgia (1); none investigated lamotrigine in acute pain. The update had five additional studies (1111 additional participants). Participants were aged between 26 and 77 years. Study duration was 2 weeks in one study and at least 6 weeks in the remainder; eight were of eight week duration or longer. There is no convincing evidence that lamotrigine is effective in treating acute or chronic pain at doses of about 200-400 mg daily. Almost 10% of participants taking lamotrigine reported a skin rash.
AUTHORS' CONCLUSIONS
The additional studies tripled participant numbers providing data for analysis, and new, more stringent criteria for outcomes and analysis were used; conclusions about lamotrigine's lack of efficacy in chronic pain did not change. Given availability of more effective treatments including antiepileptics and antidepressant medicines, lamotrigine does not have a significant place in therapy based on available evidence.
Topics: Acute Disease; Analgesics; Chronic Disease; Humans; Lamotrigine; Pain; Randomized Controlled Trials as Topic; Triazines
PubMed: 21328280
DOI: 10.1002/14651858.CD006044.pub3 -
Acta Medica Iranica Jul 2015Lamotrigine is a safe anti-epileptic drug among pregnant and lactating women. Some concerns exist regarding the safety of lamotrigine during breastfeeding and related... (Review)
Review
Lamotrigine is a safe anti-epileptic drug among pregnant and lactating women. Some concerns exist regarding the safety of lamotrigine during breastfeeding and related neonatal complications. In this brief review, this matter was evaluated and discussed. In this review study, the medical literature available in search databases such as Embase, Scopus, PubMed, and Medline and even also local medical search engines were evaluated. The results indicated that lamotrigine is a safe anti-epileptic drug for breastfeeding women with rare and usually mild adverse effects among neonates exposed to high milk concentration of this drug and its metabolites. However, close periodical monitoring for infants whose mothers are utilizing lamotrigine is recommended to decrease the probability of severe side effects among them.
Topics: Adult; Anticonvulsants; Breast Feeding; Epilepsy; Female; Humans; Infant; Infant, Newborn; Lactation; Lamotrigine; Mothers; Pregnancy; Pregnancy Complications; Triazines
PubMed: 26520624
DOI: No ID Found -
Pharmacogenetics and Genomics Jun 2020
Review
Topics: ATP-Binding Cassette Transporters; Anticonvulsants; Brain; Calcium Channels, Q-Type; Humans; Lamotrigine; Monosaccharide Transport Proteins; Polymorphism, Genetic; Receptors, GABA
PubMed: 32187155
DOI: 10.1097/FPC.0000000000000397