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1.
Iran J Med Sci ; 48(1): 70-76, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36688194

RESUMO

Background: Genetic diversity in human leukocyte antigen (HLA) alleles across populations is a significant risk factor for drug-induced severe cutaneous adverse reactions (SCARs), e.g., carbamazepine (CBZ)- and lamotrigine (LTG)-induced Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). The present study aimed to investigate the frequency of different HLA alleles in Iranian patients with CBZ- and LTG-induced SJS/TEN. Methods: A case-control study was conducted from 2011 to 2018 at various hospitals affiliated with Shiraz University of Medical Sciences (Shiraz, Iran). A total of 31 patients receiving anticonvulsant drugs (CZB or LTG) were recruited and divided into two groups. The drug-induced group (n=14) included hospitalized patients due to CBZ- or LTG-induced SJS/TEN. The drug-tolerant group (n=17) included individuals receiving CBZ or LTG for at least three months with no adverse effects. In addition, 46 healthy individuals (control group) were recruited. The frequency of HLA-A, -B, and -DRB1 alleles in patients with CZB- or LTG-induced SJS/TEN was investigated. HLA typing was performed using the allele-specific polymerase chain reaction method. The Chi square test and Fisher's exact test were used to determine a potential association between SJS/TEN and HLA alleles. P<0.05 was considered statistically significant. Results: CBZ- or LTG-induced SJS/TEN was not significantly associated with HLA alleles. However, HLA-DRB1*01 showed a significantly higher frequency in patients with CBZ-induced SJS/TEN than the CBZ-tolerant patients (30% vs. 9%, P=0.07). Conclusion: Overall, no significant association was found between CBZ- or LTG-induced SJS/TEN and HLA alleles. Further large-scale studies are required to substantiate our findings.


Assuntos
Anticonvulsivantes , Síndrome de Stevens-Johnson , Humanos , Anticonvulsivantes/efeitos adversos , Lamotrigina/efeitos adversos , Irã (Geográfico) , Síndrome de Stevens-Johnson/genética , Alelos , Estudos de Casos e Controles , Antígenos HLA-B/genética , Carbamazepina/efeitos adversos , Benzodiazepinas
2.
Neuroreport ; 34(1): 61-66, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36484279

RESUMO

OBJECTIVES: The anticonvulsant and antioxidant effects of lamotrigine on status epilepticus (SE) are incompletely understood. We assessed these effects of lamotrigine on pilocarpine (Pilo)-induced SE in mice. METHODS: Male C57BL/J6 mice were assigned to three groups: the control group, Pilo (400 mg/kg, s.c.)-induced SE (Pilo group) and lamotrigine (20 mg/kg, i.p.) treated (Pilo/lamotrigine group). The latency to SE of Racine's stage 3 or higher, the mortality rate within 2 h of Pilo administration, and the duration of SE until sacrifice were examined. Nitric oxide (NO), malondialdehyde and glutathione of oxidative stress biomarkers were detected in the hippocampus of the sacrificed animals in the above groups. NO was also detected in the cultured rat hippocampal neurons treated with 4 µM Pilo, Pilo+100 µM lamotrigine (Pilo/lamotrigine) and Pilo/lamotrigine+ N-methyl-D-aspartic acid (NMDA) receptor antagonist (10 µM MK-801, 3 µM ifenprodil) to examine the antioxidant effects of lamotrigine via non-NMDA-related pathways. RESULTS: lamotrigine prolonged the latency to SE, the SE duration until sacrifice, and decreased the mortality rate in mice with Pilo-induced SE. Lamotrigine also decreased hippocampal concentrations of NO and malondialdehyde and increased the concentrations of glutathione in the SE model. Furthermore, there were significant differences in NO concentrations between groups of cultured rat hippocampal neurons treated with Pilo and Pilo/lamotrigine, and with Pilo/lamotrigine and Pilo/lamotrigine+MK-801. CONCLUSION: Our findings suggest that lamotrigine exerts anticonvulsant and antioxidant effects on SE, but its antioxidant activity may not be fully exerted via NMDA-related pathways.


Assuntos
Pilocarpina , Estado Epiléptico , Animais , Masculino , Camundongos , Ratos , Pilocarpina/toxicidade , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Lamotrigina/efeitos adversos , Maleato de Dizocilpina , Camundongos Endogâmicos C57BL , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/metabolismo , Hipocampo/metabolismo , Glutationa/metabolismo
3.
Drug Deliv ; 30(1): 2163321, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36579655

RESUMO

Lamotrigine. (LMT) is a triazine drug has an antiepileptic effect but with low water solubility, dissolution rate and thus therapeutic effect. Spanlastics are nano-vesicular carriers' act as site-specific drug delivery system. Intranasal route could direct the drug from nose to brain and provide a faster and more specific therapeutic effect. Therefore, this study aimed to upload lamotrigine onto nano-vesicles using spanlastic nasal insert delivery for effective epilepsy treatment via overcoming lamotrigine's low solubility and improving its bioavailability. Lamtrigine-loaded nano-spanlastic vesicles were prepared by ethanol injection method. To study different formulation factor's effect on formulations characters; particle size (PS), Zeta potential (ZP), polydispersity index (PDI), entrapment efficiency percentage (EE%) and LMT released amount after 6 h (Q6h); 2^1 and 3^1 full factorial designs were employed. Optimized formula was loaded in lyophilized nasal inserts formulation which were characterized for LMT release and mucoadhesion. Pharmacokinetics studies in plasma and brain were performed on rats to investigate drug targeting efficiency. The optimal nano-spanlastic formulation (F4; containing equal Span 60 amount (100 mg) and edge activator; Tween 80) exhibited nano PS (174.2 nm), high EE% (92.75%), and Q6h > 80%. The prepared nasal inserts (S4) containing 100 mg HPMC has a higher mucoadhesive force (9319.5 dyne/cm2) and dissolution rate (> 80% within 10 min) for rapid in vivo bio-distribution. In vivo studies showed considerable improvement brain and plasma's rate and extent absorption after intranasal administration indicating a high brain targeting efficiency. The results achieved indicate that nano-spanlastic nasal-inserts offer a promising LMT brain targeting in order to maximize its antiepileptic effect.


Assuntos
Anticonvulsivantes , Epilepsia , Ratos , Animais , Lamotrigina/farmacologia , Anticonvulsivantes/farmacologia , Portadores de Fármacos , Sistemas de Liberação de Medicamentos/métodos , Encéfalo , Administração Intranasal , Epilepsia/tratamento farmacológico , Tamanho da Partícula
5.
J Int Med Res ; 50(11): 3000605221133988, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36418928

RESUMO

Lamotrigine is an antiepileptic drug that can be used to control many types of seizures as a single-agent or an add-on therapy in patients over 2 years of age. In addition to common adverse reactions, this current case report describes a paediatric male patient with a rare side-effect of persistent penile erectile due to lamotrigine. Previous studies have shown that it can improve sexual function in adult male patients. This patient suffered from refractory epilepsy and pneumonia. He had taken a variety of antiepileptic drugs for a long time and developed priapism after the dosage of lamotrigine had been increased. The priapism improved after drug withdrawal and sedation. Further research is needed to elucidate the mechanism of this rare side-effect.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Epilepsia , Priapismo , Adulto , Humanos , Masculino , Criança , Lamotrigina/efeitos adversos , Anticonvulsivantes/efeitos adversos , Priapismo/induzido quimicamente , Priapismo/tratamento farmacológico , Epilepsia/tratamento farmacológico , Triazinas/efeitos adversos
6.
Epileptic Disord ; 24(6): 1-13, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36193017

RESUMO

We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants, and the wellbeing of infants breastfed by mothers on ASM treatment. Information was extracted from 85 relevant articles. No data on ASM levels in breastmilk or in breastfed infants was identified for cannabidiol, cenobamate, clobazam, eslicarbazepine-acetate, everolimus, felbamate, fenfluramine, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin. For ASMs, with available information on levels in breastfed infants, very low concentrations (in the order of 10% or less of maternal serum concentrations) were reported for carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, valproate, and clonazepam. Slightly higher levels (up to approximately 30% of maternal serum concentrations) have been observed with lamotrigine and topiramate, and in single case reports for brivaracetam, lacosamide, and perampanel. High infant levels (30% up to 100% of maternal serum concentrations) have been reported with ethosuximide, phenobarbital and zonisamide. Adverse infant effects during breastfeeding by mothers on ASMs appear to be rare regardless of the type of ASM, but systematic study is limited. Prospective long-term follow-up studies of developmental outcomes among children who have been breastfed by mothers taking ASMs are sparse and have mainly involved children whose mothers were taking carbamazepine, lamotrigine, levetiracetam, phenytoin or valproate as monotherapy while breastfeeding. Although these studies have not indicated poorer outcome among breastfed children compared with those who were not breastfed, further data on long-term outcomes are needed to draw firm conclusions. It is concluded that breastfeeding should in general be encouraged in women taking ASMs, given the well-established benefits of breastfeeding with regard to both short- and long-term infant health in the general population. Counselling needs to be individualized including information on the current knowledge regarding the woman's specific ASM treatment.


Assuntos
Canabidiol , Epilepsia , Aleitamento Materno , Carbamazepina/uso terapêutico , Criança , Clobazam/uso terapêutico , Clonazepam/uso terapêutico , Epilepsia/tratamento farmacológico , Etossuximida/uso terapêutico , Everolimo/uso terapêutico , Felbamato/uso terapêutico , Feminino , Fenfluramina/uso terapêutico , Gabapentina/uso terapêutico , Humanos , Lactente , Lacosamida , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Oxcarbazepina , Fenobarbital/uso terapêutico , Fenitoína/uso terapêutico , Estudos Prospectivos , Tiagabina , Topiramato , Ácido Valproico/uso terapêutico , Vigabatrina/uso terapêutico , Zonisamida/uso terapêutico
8.
Int J Pharm ; 628: 122310, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36270552

RESUMO

Multi-component pharmaceutical systems such as cocrystal and salt have gained popularity in academia and industry due to their ability to regulate the poor physicochemical properties of active pharmaceutical ingredients (APIs). However, different crystal states, namely polymorphs are becoming a key factor influencing future clinical drug safety. It remains an under explored field, particularly how to hit the polymorphs of multi-components system quickly and effectively. For the first time, a novel drug-drug salt of lamotrigine (LAM)-tolfenamic acid (TOL) with two polymorphs and two solvates were discovered in this study. Forms I and II exist in rhombohedral and block crystal morphologies, whereas methanol and ethanol solvates are crystallized as rods and flakes, respectively. Further physicochemical properties were characterized and compared between parent compounds and the four crystal forms. The apparent solubilities of the new four crystal forms were higher than TOL but lower than LAM. The intrinsic dissolution rates of all crystal forms at 37.0 °C followed a similar trend, and all crystal forms were non-hygroscopic (<1.0%). Two stable polymorphs provide a new choice for the further formulation development.


Assuntos
Cristalização , Lamotrigina , Solubilidade , Preparações Farmacêuticas
9.
PLoS One ; 17(10): e0276012, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36227855

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of different antidepressants and anticonvulsants in the treatment of central poststroke pain (CPSP) by network meta-analysis and provide an evidence-based foundation for clinical practice. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, APA PsycINFO, Wanfang, VIP and other databases were searched by computer to find clinical randomized controlled studies (RCTs) on drug treatment of CPSP. The retrieval time limit was from the establishment of each database to July 2022. The quality of the included RCTs was evaluated using the bias risk assessment tool recommended by Cochrane. Stata 14.0 was used for network meta-analysis. RESULTS: A total of 13 RCTs, 1040 patients and 9 drugs were finally included. The results of the network meta-analysis showed that the effectiveness ranking as rated by the visual analog scale (VAS) was gabapentin > pregabalin > fluoxetine > lamotrigine > duloxetine > serqulin > amitriptyline > carbamazepine > vitamin B. Ranking according to the numerical rating scale (NRS) was pregabalin > gabapentin > carbamazepine. Ranking derived from the Hamilton depression scale (HAMD) was pregabalin > duloxetine > gabapentin > amitriptyline. CONCLUSION: All nine drugs can relieve the pain of CPSP patients to different degrees; among them pregabalin and gabapentin have the most significant effect, and gabapentin and pregabalin also have the most adverse reactions. In the future, more multicenter, large sample, double-blind clinical randomized controlled trials need to be carried out to supplement and demonstrate the results of this study.


Assuntos
Anticonvulsivantes , Neuralgia , Amitriptilina/uso terapêutico , Anticonvulsivantes/efeitos adversos , Antidepressivos/efeitos adversos , Carbamazepina/uso terapêutico , Cloridrato de Duloxetina/uso terapêutico , Fluoxetina/uso terapêutico , Gabapentina/uso terapêutico , Humanos , Lamotrigina/uso terapêutico , Estudos Multicêntricos como Assunto , Metanálise em Rede , Neuralgia/tratamento farmacológico , Pregabalina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitaminas/uso terapêutico
10.
Pharmazie ; 77(7): 255-261, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36199180

RESUMO

The aim of the present study was to survey adverse drug events (ADEs) in patients with bipolar disorders and identify risk factors using the Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system. Data on patients with bipolar disorders were extracted from the JADER database. The Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PT) and standardized MedDRA queries (SMQ) were used to define ADEs. A multiple logistic regression analysis was performed to identify risk factors for ADEs. A total of 8653 reports of 1108 types of ADEs (PT) were registered in data collected on 3521 patients with bipolar disorders. Rash (PT) was the most frequently reported in 549 patients, followed by drug eruption (PT) in 387, fever (PT) in 364, toxicity to various agents (PT) in 291, and Stevens-Johnson syndrome (PT) in 261. Among 24 ADEs (PT) that were reported in more than 50 patients, lamotrigine was associated with increased risks of 13 ADEs (PT), followed by carbamazepine with increased risks of 8 ADEs (PT). The majority of these ADEs belonged to hypersensitivity (SMQ) or hepatic disorder (SMQ). Lithium carbonate was associated with increased risks of rash (PT), drug interaction (PT), and tubulointerstitial diseases (SMQ). All antipsychotics increased the adjusted odds ratio for neuroleptic malignant syndrome (PT). The risk of hyperglycemia/new onset diabetes mellitus (SMQ) was increased by olanzapine, quetiapine fumarate, and risperidone. We are presenting the profiles of ADEs in patients with bipolar disorders using the JADER database, and propose risk factors for 19 ADEs (PT) and 4 ADEs (SMQ).


Assuntos
Antipsicóticos , Transtorno Bipolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Sistemas de Notificação de Reações Adversas a Medicamentos , Antipsicóticos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Carbamazepina , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Exantema/induzido quimicamente , Exantema/epidemiologia , Humanos , Japão/epidemiologia , Lamotrigina/efeitos adversos , Carbonato de Lítio/efeitos adversos , Olanzapina/efeitos adversos , Fumarato de Quetiapina/efeitos adversos , Risperidona/efeitos adversos
11.
BMC Med Inform Decis Mak ; 22(1): 262, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-36207697

RESUMO

BACKGROUND: Dementia is a group of symptoms that largely affects older people. The majority of patients face behavioural and psychological symptoms (BPSD) during the course of their illness. Alzheimer's disease (AD) and vascular dementia (VaD) are two of the most prevalent types of dementia. Available medications provide symptomatic benefits and provide relief from BPSD and associated health issues. However, it is unclear how specific dementia, antidepressant, antipsychotic, antianxiety, and mood stabiliser drugs, used in the treatment of depression and dementia subtypes are prescribed in hospital admission, during hospital stay, and at the time of discharge. To address this, we apply multi-dimensional data analytical approaches to understand drug prescribing practices within hospitals in England and Wales. METHODS: We made use of the UK National Audit of Dementia (NAD) dataset and pre-processed the dataset. We evaluated the pairwise Pearson correlation of the dataset and selected key data features which are highly correlated with dementia subtypes. After that, we selected drug prescribing behaviours (e.g. specific medications at the time of admission, during the hospital stay, and upon discharge), drugs and disorders. Then to shed light on the relations across multiple features or dimensions, we carried out multiple regression analyses, considering the number of dementia, antidepressant, antipsychotic, antianxiety, mood stabiliser, and antiepileptic/anticonvulsant drug prescriptions as dependent variables, and the prescription of other drugs, number of patients with dementia subtypes (AD/VaD), and depression as independent variables. RESULTS: In terms of antidepressant drugs prescribed in hospital admission, during stay and discharge, the number of sertraline and venlafaxine prescriptions were associated with the number of VaD patients whilst the number of mirtazapine prescriptions was associated with frontotemporal dementia patients. During admission, the number of lamotrigine prescriptions was associated with frontotemporal dementia patients, and with the number of valproate and dosulepin prescriptions. During discharge, the number of mirtazapine prescriptions was associated with the number of donepezil prescriptions in conjunction with frontotemporal dementia patients. Finally, the number of prescriptions of donepezil/memantine at admission, during hospital stay and at discharge exhibited positive association with AD patients. CONCLUSION: Our analyses reveal a complex, multifaceted set of interactions among prescribed drug types, dementia subtypes, and depression.


Assuntos
Antipsicóticos , Dotiepina , Demência Frontotemporal , Idoso , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/epidemiologia , Donepezila/uso terapêutico , Dotiepina/uso terapêutico , Demência Frontotemporal/tratamento farmacológico , Hospitais , Humanos , Lamotrigina/uso terapêutico , Memantina/uso terapêutico , Mirtazapina/uso terapêutico , NAD/uso terapêutico , Sertralina/uso terapêutico , Ácido Valproico/uso terapêutico , Cloridrato de Venlafaxina/uso terapêutico , País de Gales/epidemiologia
12.
Genes (Basel) ; 13(10)2022 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-36292706

RESUMO

The association between autism spectrum disorders (ASD) and epilepsy has been extensively documented, and the estimated prevalence varies depending upon the selected population and the clinical characteristics. Currently, there are a lack of studies assessing the patient care pathways in ASD, particularly for comorbidity with epilepsy, despite its personal, familial, and economic impacts. Genetic abnormalities are likely implicated in the association of ASD and epilepsy, although they are currently detectable in only a small percentage of patients, and some known genetic and medical conditions are associated with ASD and epilepsy. There is no specificity of seizure type to be expected in children and adolescents with ASD compared with other neurodevelopmental disorders or epileptic syndromes. Treatment options include antiepileptic drugs (AED) and developmentally-based early interventions for ASD. Carbamazepine and lamotrigine are the most used AED, but further studies are needed to more precisely define the most suitable medications for this specific group of children with ASD.


Assuntos
Transtorno Autístico , Epilepsia , Criança , Adolescente , Humanos , Anticonvulsivantes/uso terapêutico , Transtorno Autístico/tratamento farmacológico , Transtorno Autístico/genética , Lamotrigina/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia/genética , Carbamazepina/uso terapêutico
13.
Acta Clin Croat ; 61(Suppl 1): 88-92, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36304802

RESUMO

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome (DIHS), is an under-recognized and potentially life-threatening hypersensitivity reaction associated with a variety of medications, many of them anti-epileptics. Patients with DRESS syndrome typically present with rash, swelling, fever, and systemic manifestations. We report a case of a patient admitted to out hospital after the administration of an anticonvulsive drug lamotrigine. She was presented with high fever, rash, face oedema and elevated liver enzymes. At admission, all previous medications were discontinued, systemic corticosteroid therapy was administered, and the patient was monitored for signs of clinical recovery. This case report suggests that in patients presenting with skin rash and systemic abnormalities after a recent change in medications, physicians should consider DRESS syndrome as a possible diagnosis and switch to a more aggressive therapy if removal of the offending agent does not result in clinical improvement. Early diagnosis can reduce the risk of complications and the mortality rate.


Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Eosinofilia , Exantema , Feminino , Humanos , Lamotrigina/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Síndrome de Hipersensibilidade a Medicamentos/complicações , Anticonvulsivantes/efeitos adversos , Eosinofilia/induzido quimicamente , Eosinofilia/complicações , Eosinofilia/diagnóstico , Exantema/induzido quimicamente , Exantema/diagnóstico , Exantema/complicações
14.
CNS Drugs ; 36(10): 1079-1111, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36194365

RESUMO

The developmental and epileptic encephalopathies encompass a group of rare syndromes characterised by severe drug-resistant epilepsy with onset in childhood and significant neurodevelopmental comorbidities. The latter include intellectual disability, developmental delay, behavioural problems including attention-deficit hyperactivity disorder and autism spectrum disorder, psychiatric problems including anxiety and depression, speech impairment and sleep problems. Classical examples of developmental and epileptic encephalopathies include Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. The mainstay of treatment is with multiple anti-seizure medications (ASMs); however, the ASMs themselves can be associated with psychobehavioural adverse events, and effects (negative or positive) on cognition and sleep. We have performed a targeted literature review of ASMs commonly used in the treatment of developmental and epileptic encephalopathies to discuss the latest evidence on their effects on behaviour, mood, cognition, sedation and sleep. The ASMs include valproate (VPA), clobazam, topiramate (TPM), cannabidiol (CBD), fenfluramine (FFA), levetiracetam (LEV), brivaracetam (BRV), zonisamide (ZNS), perampanel (PER), ethosuximide, stiripentol, lamotrigine (LTG), rufinamide, vigabatrin, lacosamide (LCM) and everolimus. Bromide, felbamate and other sodium channel ASMs are discussed briefly. Overall, the current evidence suggest that LEV, PER and to a lesser extent BRV are associated with psychobehavioural adverse events including aggressiveness and irritability; TPM and to a lesser extent ZNS are associated with language impairment and cognitive dulling/memory problems. Patients with a history of behavioural and psychiatric comorbidities may be more at risk of developing psychobehavioural adverse events. Topiramate and ZNS may be associated with negative effects in some aspects of cognition; CBD, FFA, LEV, BRV and LTG may have some positive effects, while the remaining ASMs do not appear to have a detrimental effect. All the ASMs are associated with sedation to a certain extent, which is pronounced during uptitration. Cannabidiol, PER and pregabalin may be associated with improvements in sleep, LTG is associated with insomnia, while VPA, TPM, LEV, ZNS and LCM do not appear to have detrimental effects. There was variability in the extent of evidence for each ASM: for many first-generation and some second-generation ASMs, there is scant documented evidence; however, their extensive use suggests favourable tolerability and safety (e.g. VPA); second-generation and some third-generation ASMs tend to have the most robust evidence documented over several years of use (TPM, LEV, PER, ZNS, BRV), while evidence is still being generated for newer ASMs such as CBD and FFA. Finally, we discuss how a variety of factors can affect mood, behaviour and cognition, and untangling the associations between the effects of the underlying syndrome and those of the ASMs can be challenging. In particular, there is enormous heterogeneity in cognitive, behavioural and developmental impairments that is complex and can change naturally over time; there is a lack of standardised instruments for evaluating these outcomes in developmental and epileptic encephalopathies, with a reliance on subjective evaluations by proxy (caregivers); and treatment regimes are complex involving multiple ASMs as well as other drugs.


Assuntos
Transtorno do Espectro Autista , Canabidiol , Espasmos Infantis , Brometos , Clobazam , Cognição , Etossuximida , Everolimo , Felbamato , Fenfluramina , Humanos , Lacosamida , Lamotrigina , Levetiracetam , Pregabalina , Sulfetos , Topiramato , Ácido Valproico , Vigabatrina , Compostos de Zinco , Zonisamida
16.
J Matern Fetal Neonatal Med ; 35(25): 10158-10161, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36093852

RESUMO

OBJECTIVE: To determine which antiepileptic drugs pregnant women receive by trimester. METHODS: This retrospective cohort study using the IBM Watson Health MarketScan Research Databases evaluated which antiepileptic drugs pregnant women with epilepsy received by trimester. Women with aged 15-54 years with a history of seizure disorder who underwent a delivery hospitalization between 2008 and 2017 were included in the analysis. Descriptive statistics were performed. RESULTS: Of 34,144 women with a seizure disorder diagnosis and a delivery hospitalization, 10,289 (30.1%) received an anti-epileptic medication during pregnancy of which more than half received lamotrigine or levetiracetam. Other antiepileptic medications used by >5% of the population during any one trimester in the study period included carbamazepine, clonazepam, and topiramate. In evaluating medication use in the 1st trimester versus the 2nd trimester, clonazepam use decreased 32.0% (95% CI 60.0%, 77.0%) from 5.6% to 3.8% of patients receiving antiepileptics from the 1st to the 2nd trimester, gabapentin deceased 22.1% (95% CI 0.68%, 0.90%) from 4.1% to 3.2%, and topiramate decreased 30.0% (95% CI 62.8%, 77.9%) from 7.2% to 5.1%. In comparison, levetiracetam increased from 22.5% to 33.3% between the 1st and 3rd trimester and lamotrigine 22.2% to 27.5% between the 1st and 3rd trimester, 48.3% and 24.0% increases respectively. CONCLUSION: Antiepileptic drugs with less favorable fetal risk profiles such as topiramate decreased by trimester while medications with more favorable fetal risk profiles such as lamotrigine and levetiracetam increased. These findings broadly support that there are opportunities to improve pre-conceptional counseling of women with epilepsy.


Assuntos
Anticonvulsivantes , Epilepsia , Feminino , Humanos , Gravidez , Anticonvulsivantes/uso terapêutico , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Topiramato/uso terapêutico , Estudos Retrospectivos , Clonazepam/uso terapêutico , Epilepsia/tratamento farmacológico
17.
J Affect Disord ; 318: 386-392, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36103936

RESUMO

BACKGROUND: For bipolar disorder, a severe, recurring mental disorder, pharmacotherapy is a cornerstone of effective treatment. The purpose of this study was to investigate prescribing changes among patients with bipolar disorder discharged from two public psychiatric hospitals in Taiwan over a 14-year period. METHODS: Patients with bipolar disorder discharged from the two study hospitals between 2006 and 2019 (n = 9071) were included in the analysis. Prescribed drugs for the treatment of bipolar disorder, including mood stabilizers (i.e., lithium, valproate, carbamazepine, and lamotrigine), any antipsychotics (i.e., second- and first-generation antipsychotics; SGAs & FGAs), and any antidepressants, were examined. Complex polypharmacy was defined as the use of 3 or more agents among the prescribed drugs. Temporal trends of each prescribing pattern were analyzed using the Cochran-Armitage Trend test. RESULTS: The prescription rates of SGAs, any antidepressants, antidepressant monotherapy, antidepressants without mood stabilizers, and complex polypharmacy significantly increased over time, whereas the prescription rates of any mood stabilizers, lithium, carbamazepine, FGAs, and antidepressants plus mood stabilizers significantly decreased. LIMITATIONS: Treatment allocation is not randomized in a retrospective study. The diagnoses of bipolar disorder were based on clinical judgments. This was a hospital-based study. CONCLUSIONS: Substantial prescribing changes took place during the study period. The decreased use of lithium and the increased use of antidepressants were not in accordance with the evidence-based treatment and recommendations in treatment guidelines. Therefore, long-term outcomes of prescribing changes should be explored in the future.


Assuntos
Antipsicóticos , Transtorno Bipolar , Anticonvulsivantes/uso terapêutico , Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Benzodiazepinas/uso terapêutico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Carbamazepina/uso terapêutico , Hospitais Psiquiátricos , Humanos , Lamotrigina/uso terapêutico , Lítio/uso terapêutico , Alta do Paciente , Estudos Retrospectivos , Taiwan , Ácido Valproico/uso terapêutico
18.
Transl Psychiatry ; 12(1): 359, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36055984

RESUMO

Lithium (Li) is a well-established mood disorder treatment and may be neuroprotective. Bi-directional regulation (i.e. affecting manic symptoms and depressive symptoms) by Li has not been demonstrated. This study explored: (1) bidirectional regulation by Li in murine models of depression, mania, and bipolar disorder (BP); and (2) potential Li synergism with antidepressant/anti-mania agents. The chronic unpredictable mild stress (CUMS) and ketamine-induced mania (KM) models were used. These methods were used in series to produce a BP model. In vivo two-photon imaging was used to visualize Ca2+ activity in the dorsolateral prefrontal cortex. Depressiveness, mania, and cognitive function were assessed with the forced swim task (FST), open field activity (OFA) task, and novel object recognition task, respectively. In CUMS mice, Ca2+ activity was increased strongly by Li and weakly by lamotrigine (LTG) or valproate (VPA), and LTG co-administration reduced Li and VPA monotherapy effects; depressive immobility in the FST was attenuated by Li or LTG, and attenuated more strongly by LTG-VPA or LTG-Li; novel object exploration was increased strongly by Li and weakly by LTG-Li, and reduced by LTG, VPA, or LTG-VPA. In KM mice, Li or VPA attenuated OFA mania symptoms and normalized Ca2+ activity partially; Li improved cognitive function while VPA exacerbated the KM alteration. These patterns were replicated in the respective BP model phases. Lithium had bi-directional, albeit weak, mood regulation effects and a cognitive supporting effect. Li co-administration with antidepressant/-manic agents enhanced mood-regulatory efficacy while attenuating their cognitive-impairing effects.


Assuntos
Transtorno Bipolar , Disfunção Cognitiva , Animais , Anticonvulsivantes/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Transtorno Bipolar/psicologia , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças , Lamotrigina/farmacologia , Lamotrigina/uso terapêutico , Lítio/farmacologia , Lítio/uso terapêutico , Camundongos , Ácido Valproico
19.
Epilepsy Behav ; 135: 108904, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36095876

RESUMO

OBJECTIVE: The management of pregnant women with epilepsy (WWE) treated with antiepileptic drugs (AEDs) polytherapy poses a great challenge. The purpose of this study was to evaluate the major congenital malformations (MCMs) associated with AED polytherapy, to assess the impacts of polytherapy regimens on seizure control and breastfeeding, and to determine the potential predictors for pregnancy outcomes. METHODS: This study was based on prospectively acquired data from a registry enrolling WWE in early pregnancy from Feb 2010 to July 2019, in which 123 pregnancies in 110 WWE were exposed to 27 different AED combinations. RESULTS: There were 123 pregnancies in 110 WWE analyzed in our study. The live birth rate was 86.2 % and the risk of MCMs was 10.4 %. Multivariate analysis indicated that prenatal exposure to phenobarbital (odds ratio [OR], 17.424; 95 %CI, 1.510-201.067; P = 0.022) and topiramate (OR, 9.469; 95 %CI, 1.149-62.402; P = 0.036) was associated with increased risk of MCMs. Valproate (OR, 4.441; 95 %CI, 1.165-16.934; P = 0.029), phenobarbital (OR, 13.636; 95 %CI, 2.146-86.660; P = 0.006) and topiramate (OR, 7.527; 95 %CI, 1.764-32.118; P = 0.006) were significantly correlated with adverse pregnancy outcomes. Among 67 pregnancies in four combinations over 10 patients, 15 (22.4 %) remained seizure free through pregnancy, seizure frequency increased in 17 (25.4 %), decreased in 24 (35.8 %) women, in 26 (38.8 %) remained unchanged. Only 23.6 % of mothers undertook exclusive breastfeeding. Planned pregnancy was the only independent factor significantly associated with decreased risk of adverse pregnancy outcomes (OR, 0.139; 95 % CI, 0.051-0.382; P < 0.001). Notably, no adverse pregnancy outcome was recorded in pregnancies exposed to the combination of lamotrigine plus levetiracetam. CONCLUSION: Prenatal exposure to the combinations containing valproate, phenobarbital, or topiramate was associated with increased risk of adverse pregnant outcomes. AED-related teratogenicity may be reduced by planned pregnancy in WWE exposed to polytherapy. Our findings also suggest the combination of lamotrigine and levetiracetam seems to be most desirable to balance seizure control and fetal safety.


Assuntos
Epilepsia , Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Anticonvulsivantes/efeitos adversos , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Masculino , Fenobarbital/efeitos adversos , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Sistema de Registros , Topiramato/uso terapêutico , Ácido Valproico/efeitos adversos
20.
Sci Total Environ ; 852: 158391, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36049679

RESUMO

The occurrence of 200 multiclass contaminants of emerging concern (CECs) encompassing 168 medicinal products and transformation products (TPs), 5 artificial sweeteners, 12 industrial chemicals, and 15 other compounds was investigated in influent and effluent wastewater samples collected during 7 consecutive days from 5 wastewater treatment plants (WWTPs) located in Cyprus. The methodology included a generic solid-phase extraction protocol using mixed-bed cartridges followed by Ultra-High Performance Liquid Chromatography coupled with Quadrupole-Time of Flight Mass Spectrometry (UHPLC-QTOF-MS) analysis. A total of 63 CECs were detected at least in one sample, with 52 and 55 out of the 200 compounds detected in influents and effluents, respectively. Ten (10) out of the 24 families of parent compounds and associated TPs were found in the wastewater samples (influent or effluent). 1-H-benzotriazole, carbamazepine, citalopram, lamotrigine, sucralose, tramadol, and venlafaxine (>80 % frequency of appearance in effluents) were assessed with respect to their bioavailability in soil as part of different scenarios of irrigation with reclaimed water following a qualitative approach. A high score of 12 (high probability) was predicted for 2 scenarios, a low score of 3 (rare occasions) for 2 scenarios, while the rest 28 scenarios had scores 5-8 (unlikely or limited possibility) and 9-11 (possibly). Retrospective screening was performed with the use of a target database of 2466 compounds and led to the detection of 158 additional compounds (medicinal products (65), medicinal products TPs (15), illicit drugs (7), illicit drugs TPs (3), industrial chemicals (11), plant protection products (25), plant protection products TPs (10), and various other compounds (22). This work aspires to showcase how the presence of CECs in wastewater could be investigated and assessed at WWTP level, including an expert-based methodology for assessing the soil bioavailability of CECs, with the aim to develop sustainable practices and enhance reclaimed water reuse.


Assuntos
Drogas Ilícitas , Tramadol , Poluentes Químicos da Água , /química , Poluentes Químicos da Água/análise , Solo , Água/análise , Disponibilidade Biológica , Estudos Retrospectivos , Cloridrato de Venlafaxina , Lamotrigina , Citalopram , Carbamazepina/análise , Edulcorantes/análise
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