RESUMO
Cysteinyl leukotrienes (CysLTs) are central to the pathophysiology of asthma and various inflammatory disorders. Leukotriene receptor antagonists (LTRAs) effectively treat respiratory conditions by targeting cysteinyl leukotriene receptors, CysLT1 and CysLT2 subtypes. This review explores the multifaceted effects of LTs, extending beyond bronchoconstriction. CysLT receptors are not only present in the respiratory system but are also crucial in neuronal signaling pathways. LTRAs modulate these receptors, influencing downstream signaling, calcium levels, inflammation, and oxidative stress (OS) within neurons hinting at broader implications. Recent studies identify novel molecular targets, sparking interest in repurposing LTRAs for therapeutic use. Clinical trials are investigating their potential in neuroinflammation control, particularly in Alzheimer's disease (AD) and Parkinson's diseases (PD). However, montelukast, a long-standing LTRA since 1998, raises concerns due to neuropsychiatric adverse drug reactions (ADRs). Despite widespread use, understanding montelukast's metabolism and underlying ADR mechanisms remains limited. This review comprehensively examines LTRAs' diverse biological effects, emphasizing non-bronchoconstrictive activities. It also analyses plausible mechanisms behind LTRAs' neuronal effects, offering insights into their potential as neurodegenerative disease modulators. The aim is to inform clinicians, researchers, and pharmaceutical developers about LTRAs' expanding roles, particularly in neuroinflammation control and their promising repurposing for neurodegenerative disease management.
Assuntos
Antagonistas de Leucotrienos , Receptores de Leucotrienos , Humanos , Antagonistas de Leucotrienos/uso terapêutico , Antagonistas de Leucotrienos/farmacologia , Antagonistas de Leucotrienos/efeitos adversos , Animais , Receptores de Leucotrienos/metabolismo , Sulfetos/uso terapêutico , Sulfetos/farmacologia , Sulfetos/efeitos adversos , Acetatos/uso terapêutico , Acetatos/farmacologia , Acetatos/efeitos adversos , Neurotransmissores/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ciclopropanos , QuinolinasAssuntos
Acetatos , Ciclopropanos , Psicoses Induzidas por Substâncias , Quinolinas , Sulfetos , Adolescente , Criança , Humanos , Acetatos/efeitos adversos , Acetatos/uso terapêutico , Asma/tratamento farmacológico , Ciclopropanos/efeitos adversos , Psicoses Induzidas por Substâncias/etiologia , Quinolinas/efeitos adversos , Sulfetos/efeitos adversosRESUMO
BACKGROUND: Depression and dementia are highly prevalent in older adults and often co-occur. This Phase IV study investigated the effectiveness and tolerability of vortioxetine in improving depressive symptoms, cognitive performance, daily and global functioning and health-related quality of life (HRQoL) in patients with major depressive disorder (MDD) and comorbid early-stage dementia. METHODS: Patients (n = 82) aged 55-85 years with a primary diagnosis of MDD (onset before age 55 years) and comorbid early-stage dementia (diagnosed ≥6 months before screening and after onset of MDD; Mini-Mental State Examination-2 total score, 20-24) received vortioxetine for 12 weeks (initiated at 5 mg/day and up-titrated to 10 mg/day at day 8, with flexible dosing thereafter [5-20 mg/day]). The primary endpoint was change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 12. RESULTS: Significant improvement in depressive symptom severity was seen from week 1 onwards (P < 0.0001). At week 12, the least-square mean (standard error) change in MADRS total score from baseline was -12.4 (0.78). Significant improvements in cognitive performance were observed (from week 1 for the Digit Symbol Substitution Test and week 4 for the Rey Auditory Verbal Learning Test). Patients also experienced significant improvements in daily and global functioning, and HRQoL. Vortioxetine was well tolerated. From week 4 onwards, more than 50 % of patients were receiving 20 mg/day. LIMITATIONS: Open-label study. CONCLUSIONS: Vortioxetine demonstrated effectiveness in clinically significantly improving depressive symptoms, cognitive performance, daily and global functioning, and HRQoL in patients with MDD and comorbid early-stage dementia treated for 12 weeks. TRIAL REGISTRATION: ClinicalTrials.gov/ct2/show/NCT04294654.
Assuntos
Demência , Transtorno Depressivo Maior , Humanos , Idoso , Vortioxetina/uso terapêutico , Transtorno Depressivo Maior/psicologia , Qualidade de Vida , Piperazinas/efeitos adversos , Método Duplo-Cego , Demência/induzido quimicamente , Resultado do Tratamento , Sulfetos/efeitos adversosRESUMO
BACKGROUND: Vortioxetine has demonstrated dose-dependent efficacy in patients with major depressive disorder (MDD), with the greatest effect observed with vortioxetine 20 mg/day. This analysis further explored the clinical relevance of the more rapid and greater improvement in depressive symptoms observed with vortioxetine 20 mg/day vs 10 mg/day. METHODS: Analysis of pooled data from six short-term (8-week), randomized, placebo-controlled, fixed-dose studies of vortioxetine 20 mg/day in patients with MDD (N = 2620). Symptomatic response (≥50% decrease in Montgomery-Åsberg Depression Rating Scale [MADRS] total score), sustained symptomatic response, and remission (MADRS total score ≤10) were assessed by vortioxetine dosage (20 or 10 mg/day). RESULTS: After 8 weeks, 51.4% of patients receiving vortioxetine 20 mg/day had achieved symptomatic response vs 46.0% of those receiving vortioxetine 10 mg/day (P < .05). Significantly more patients achieved symptomatic response vs placebo from week 2 onwards for vortioxetine 20 mg/day and from week 6 onwards for vortioxetine 10 mg/day (both P ≤ .05). Sustained response was achieved from week 4 for 26.0% of patients receiving vortioxetine 20 mg/day vs 19.1% of those receiving vortioxetine 10 mg/day (P < .01), increasing to 36.0% and 29.8%, respectively, over the 8-week treatment period (P < .05). At week 8, 32.0% of patients receiving vortioxetine 20 mg/day were in remission vs 28.2% of those receiving vortioxetine 10 mg/day (P = .09). Rates of adverse events and treatment withdrawal were not increased during the week following vortioxetine dose up-titration to 20 mg/day. CONCLUSION: Vortioxetine 20 mg/day provides more rapid and more sustained symptomatic response than vortioxetine 10 mg/day in patients with MDD, without compromising tolerability.
Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Piperazinas/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Sulfetos/efeitos adversos , Resultado do Tratamento , Vortioxetina/uso terapêuticoRESUMO
BACKGROUND: The two dialkylthiocarbamyl benzothiazole sulphides, dimethyl-thiocarbamylbenzothiazole sulphide (DMTBS) and diethylthio-carbamylbenzothiazole sulphide (DETBS) were shown to be good markers of both thiuram and mercaptobenzothiazole sensitivity. OBJECTIVES: To investigate if DMTBS and/or DETBS could be better markers of contact allergy to common rubber additives than the ones currently used. METHODS: Sixty-eight dermatitis patients were patch tested with DMTBS and DETBS, both at 1% in petrolatum (pet). Because of late reactions in 10 patients, these were retested to DMTBS and DETBS in serial dilutions. Tetramethylthiuram monosulphide (TMTM) 1.0% pet was also tested. RESULTS: At the initial reading Days 3 and 7, no reactions were noted to DMTBS or DETBS. At retesting, 10 of the 68 (15%) patients reacted positively to lower concentrations of DMTBS than the initial test concentration. Seven of 8 also reacted to TMTM. Three of them had positive reactions to DEBTS. All 10 patients had reactions to more diluted solutions to DMBTS than to DEBTS (p = 0.0077; Mc-Nemar test, two-sided). CONCLUSIONS: Results speak for patch test sensitization to DMTBS with cross-reactivity to TMTM and also DEBTS. DMTBS and DEBTS could be new markers of rubber allergy but a safe test concentration must be found.
Assuntos
Dermatite Alérgica de Contato , Humanos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Borracha/efeitos adversos , Alérgenos/efeitos adversos , Testes do Emplastro/efeitos adversos , Sulfetos/efeitos adversosRESUMO
BACKGROUND: Analysis of efficacy and tolerability of vortioxetine 20 mg/day, and optimal timing of dose adjustment, in patients with major depressive disorder (MDD). METHODS: Pooled analysis of six randomized, fixed-dose studies of vortioxetine 5 to 20 mg/day. Mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was analyzed by vortioxetine dose using a mixed model for repeated measures. Tolerability was assessed over the 8-week treatment period and from day 8 (ie, following dose increase to 20 mg/day). Data from three randomized, flexible-dose studies were examined for frequency and timing of dose adjustment. RESULTS: A clear dose-response relationship for vortioxetine was confirmed in terms of improvement in MADRS total score. Significant differences vs placebo were seen for vortioxetine 20 mg/day from week 2 onwards; vortioxetine 10 mg did not separate from placebo until week 4. At week 8, mean change in MADRS total score from baseline was significantly greater for vortioxetine 20 mg/day vs 10 mg/day (difference, -1.03 points; P < .05). Incidence of adverse events was not increased in patients who received vortioxetine 20 mg/day vs 10 mg/day. In flexible-dose studies, dosage was increased to 20 mg/day after 1 week in 48.0% of patients; final dosage was 20 mg/day in 64.3% of patients. CONCLUSIONS: Vortioxetine 20 mg is significantly more effective than vortioxetine 10 mg in patients with MDD, with a similar tolerability profile. In flexible-dose studies, almost half of all patients received 20 mg/day after 1 week and two-thirds received 20 mg/day as their final dosage.
Assuntos
Transtorno Depressivo Maior , Humanos , Vortioxetina/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Piperazinas/efeitos adversos , Método Duplo-Cego , Sulfetos/efeitos adversos , Resultado do TratamentoRESUMO
Importance: The evidence base for the association between montelukast and adverse neuropsychiatric outcomes is mixed and inconclusive. Several methodological limitations have been identified in the evidence base on the safety of montelukast in observational studies. Objective: To investigate the association between new montelukast exposure and 1-year incident neuropsychiatric diagnoses with improved precision and control for baseline confounders. Design, Setting, and Participants: This propensity score-matched cohort study was conducted using electronic health records from 2015 to 2019 in the TriNetX Analytics Network patient repository of more than 51 million patients from 56 health care organizations, mainly in the US. Included patients were those aged 15 to 64 years at index prescription for montelukast or for control prescription who had a history of asthma or allergic rhinitis. After propensity score matching for various baseline confounders, including comorbidities and dispensed prescription medicines, we included 154â¯946 patients, of whom 77â¯473 individuals were exposed to montelukast. Patients were followed up for 12 months. Data were analyzed from June through November 2021. Exposures: New dispensed prescription for leukotriene receptor antagonist montelukast or control medication. Main Outcomes and Measures: Incident neuropsychiatric diagnoses at 12 months identified using International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Results: There were 72â¯490 patients with asthma (44â¯726 [61.7%] women; mean [SD] age at index prescription, 35 [15] years) and 82â¯456 patients with allergic rhinitis (54â¯172 [65.7%] women; mean [SD] age at index prescription, 40 [14] years). In patients exposed to montelukast, the odds ratio [OR] for any incident neuropsychiatric outcome was 1.11 (95% CI, 1.04-1.19) in patients with asthma and 1.07 (95% CI, 1.01-1.14) in patients with allergic rhinitis compared with patients who were unexposed. The highest OR was for anxiety disorders (OR, 1.21; 95% CI, 1.05-1.20) among patients with asthma exposed to montelukast and insomnia (OR, 1.15; 95% CI, 1.05-1.27) among patients with allergic rhinitis exposed to montelukast. Conclusions and Relevance: This study found that patients with asthma or allergic rhinitis had increased odds of adverse neuropsychiatric outcomes after montelukast initiation. These findings suggest that clinicians should consider monitoring potential adverse mental health symptoms during montelukast treatment, particularly in individuals with a history of mental health or sleep problems.
Assuntos
Acetatos , Ciclopropanos , Transtornos Mentais , Quinolinas , Sulfetos , Acetatos/efeitos adversos , Adolescente , Adulto , Antiasmáticos/efeitos adversos , Asma/tratamento farmacológico , Asma/epidemiologia , Estudos de Coortes , Ciclopropanos/efeitos adversos , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Quinolinas/efeitos adversos , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/epidemiologia , Sulfetos/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: After anterior cruciate ligament (ACL) reconstruction, patient-reported outcomes are improved 10 years post-surgery; however, cytokine concentrations remain elevated years after surgery with over 80% of those with combined ACL and meniscus injuries having posttraumatic osteoarthritis (PTOA) within 10-15 years. The purpose of this multicenter, randomized, placebo-controlled trial is to assess whether a 6-month course of oral montelukast after ACL reconstruction reduces systemic markers of inflammation and biochemical and imaging biomarkers of cartilage degradation. METHODS: We will enroll 30 individuals undergoing primary ACL reconstruction to participate in this IRB-approved multicenter clinical trial. This trial will target those at greatest risk of a more rapid PTOA onset (age range 25-50 with concomitant meniscus injury). Patients will be randomly assigned to a group instructed to take 10 mg of montelukast daily for 6 months following ACL reconstruction or placebo. Patients will be assessed prior to surgery and 1, 6, and 12 months following surgery. To determine if montelukast alters systemic inflammation following surgery, we will compare systemic concentrations of prostaglandin E2, monocyte chemoattractant protein-1, and pro-inflammatory cytokines between groups. We will also compare degradative changes on magnetic resonance imaging (MRI) collected 1 and 12 months following surgery between groups with reductions in early biomarkers of cartilage degradation assessed with urinary biomarkers of type II collagen breakdown and bony remodeling. DISCUSSION: There is a complex interplay between the pro-inflammatory intra-articular environment, underlying bone remodeling, and progressive cartilage degradation. PTOA affects multiple tissues and appears to be more similar to rheumatoid arthritis than osteoarthritis with respect to inflammation. There is currently no treatment to delay or prevent PTOA after ACL injury. Since there is a larger and more persistent inflammatory response after ACL reconstruction than the initial insult of injury, treatment may need to be initiated after surgery, sustained over a period of time, and target multiple mechanisms in order to successfully alter the disease process. This study will assess whether a 6-month postoperative course of oral montelukast affects multiple PTOA mechanisms. Because montelukast administration can be safely sustained for long durations and offers a low-cost treatment option, should it be proven effective in the current trial, these results can be immediately incorporated into clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04572256 . Registered on October 1, 2020.
Assuntos
Reconstrução do Ligamento Cruzado Anterior , Quinolinas , Acetatos/efeitos adversos , Adulto , Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Ciclopropanos/efeitos adversos , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Quinolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfetos/efeitos adversosRESUMO
OBJECTIVE: To evaluate the efficacy and safety of vortioxetine in adolescents with major depressive disorder (MDD). METHOD: After 4 weeks of single-blind lead-in treatment with a Brief Psychosocial Intervention (BPI) plus placebo, patients (aged 12-17 years) with MDD (DSM-5) who did not meet response criteria (Children's Depression Rating Scale-Revised [CDRS-R]; total score ≥40 plus <40% reduction and a Parent Global Assessment score >2) were randomized 1:1:1:1 to 8 weeks of BPI plus double-blind treatment with vortioxetine 10 mg, vortioxetine 20 mg, fluoxetine 20 mg, or placebo. The primary endpoint was change from randomization in CDRS-R total score at week 8; the primary comparison was the average effect of 2 vortioxetine doses vs placebo. RESULTS: Of 784 patients enrolled in the lead-in, 616 were randomized. At week 8, the mean change in CDRS-R total score averaged for vortioxetine doses was -18.01 (SE = 0.98) and the mean difference vs placebo was 0.21 (P = .878; not significant). For fluoxetine, the mean change in CDRS-R total score was -21.95 and the mean difference vs placebo was -3.73 (P = .015). Treatment-emergent adverse events occurring in ≥5% of patients in either vortioxetine arm and at least twice more frequently than placebo were nausea, headache, vomiting, and dizziness. CONCLUSION: Patients in all groups showed reduction in CDRS-R scores by the end of the study, with no difference between combined doses of vortioxetine and placebo. The primary endpoint was not met, thereby rendering the study negative. The overall favorable safety profile of vortioxetine in an adolescent patient population was consistent with that seen in adults. CLINICAL TRIAL REGISTRATION INFORMATION: Active Reference (Fluoxetine) Fixed-Dose Study of Vortioxetine in Paediatric Patients Aged 12 to 17 Years With Major Depressive Disorder (MDD); http://clinicaltrials.gov; NCT02709746.
Assuntos
Transtorno Depressivo Maior , Vortioxetina , Adolescente , Adulto , Criança , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Fluoxetina/efeitos adversos , Humanos , Piperazinas/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Método Simples-Cego , Sulfetos/efeitos adversos , Resultado do Tratamento , Vortioxetina/farmacologia , Vortioxetina/uso terapêuticoRESUMO
Methylprednisolone (MP) is usually used to reduce inflammation reaction and tissue damage, which may have a beneficial treatment effect on coronavirus disease 2019 (COVID-19). However, we present the case of a child who manifests significant bradycardia with the use of just low dose MP on the premise of the long-term use of arbidol. Arbidol can affect the activity of CYP3A4, which is also a key metabolic enzyme of MP by competitive inhibition, and which is easy to aggravate the side effects of MP. Therefore, more attention should be paid to bradycardia occurrence in the patient with COVID-19 when MP is considered in COVID-19.
Assuntos
Anti-Inflamatórios/efeitos adversos , Bradicardia/induzido quimicamente , Tratamento Farmacológico da COVID-19 , Metilprednisolona/efeitos adversos , Antivirais/efeitos adversos , COVID-19/diagnóstico , Criança , Quimioterapia Combinada/efeitos adversos , Humanos , Indóis/efeitos adversos , Masculino , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação , Sulfetos/efeitos adversosRESUMO
OBJECTIVES: To systematically evaluate the efficacy and safety of arbidol and lopinavir/ritonavir (LPV/r) in the treatment of coronavirus disease 2019 (COVID-19) using a meta-analysis method. METHODS: The China Knowledge Network, VIP database, WanFang database PubMed database, Embase database, and Cochrane Library were searched for a collection of comparative studies on arbidol and lopinavir/ritonavir in the treatment of COVID-19. Meta-analysis was used to evaluate the efficacy and safety of Arbidol and lopinavir/ritonavir in the treatment of COVID-19. RESULTS: The results of the systematic review indicated that Arbidol had a higher positive-to-negative conversion rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid on Day 7 (p = 0.03), a higher positive-to-negative conversion rate of SARS-CoV-2 nucleic acid on Day 14 (p = 0.006), a higher improvement rate of chest computed tomography on Day 14 (p = 0.02), a lower incidence of adverse reactions (p = 0.002) and lower rate of mortality (p = 0.007). There was no difference in the rate of cough disappearance on Day 14 (p = 0.24) or the rate of severe/critical illness (p = 0.07) between the two groups. CONCLUSIONS: Arbidol may be superior to lopinavir/ritonavir in the treatment of COVID-19. However, due to the small number of included studies and the number of patients, high-quality multicenter large-sample randomized double-blind controlled trials are still needed for verification.
Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Indóis/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Sulfetos/uso terapêutico , COVID-19/mortalidade , Combinação de Medicamentos , Humanos , Indóis/efeitos adversos , Lopinavir/efeitos adversos , Ritonavir/efeitos adversos , SARS-CoV-2/efeitos dos fármacos , Sulfetos/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Cough variant asthma in children is a special type of asthma. Although there are many effective cases of combined acupuncture and western medicine in the clinical treatment of this kind of children, there is no standardized acupuncture combined with western medicine to evaluate the curative effect. Therefore, combined with existing reports, a systematic review and meta-analysis of acupuncture combined with montelukast sodium in the treatment of cough variant asthma in children were carried out to obtain conclusive results. METHODS: The following electronic databases will be searched: PubMed, the Cochrane Library, Embase, Web of Science, Medline, CNKI, Chinese Biomedical Literature Database, VIP, and Wan Fang databases. We will consider articles published between database initiation and October 2021. We will use Review Manager 5.4, provided by the Cochrane Collaborative Network for statistical analysis. Clinical randomized controlled trials related to acupuncture combined with montelukast sodium on cough variant asthma in children were included in this study. Language is limited to both Chinese and English. Research selection, data extraction, and research quality assessments were independently completed by two researchers. We then assessed the quality and risk of the included studies and observed the outcome measures. RESULTS: This study provides a high-quality synthesis to assess the effectiveness and safety of acupuncture combined with montelukast sodium on cough variant asthma in children. CONCLUSION: This systematic review will provide evidence to determine whether acupuncture combined with montelukast sodium is an effective and safe intervention for patients with cough variant asthma in children. INPLASY REGISTRATION NUMBER: INPLASY2021110006.
Assuntos
Acetatos/administração & dosagem , Terapia por Acupuntura/métodos , Antiasmáticos/administração & dosagem , Asma/terapia , Terapia Combinada/métodos , Tosse/terapia , Ciclopropanos/administração & dosagem , Quinolinas/administração & dosagem , Sulfetos/administração & dosagem , Acetatos/efeitos adversos , Antiasmáticos/efeitos adversos , Asma/tratamento farmacológico , Criança , Tosse/tratamento farmacológico , Ciclopropanos/efeitos adversos , Humanos , Metanálise como Assunto , Quinolinas/efeitos adversos , Projetos de Pesquisa , Sulfetos/efeitos adversos , Revisões Sistemáticas como Assunto , Resultado do TratamentoRESUMO
OBJECTIVE: The TREVIDA study aimed to evaluate vortioxetine for the treatment of major depressive disorder (MDD) in Taiwanese adults. METHODS: Patients with active depressive episode were recruited in this non-interventional, prospective, multi-site study conducted between June 2019 and August 2020 in Taiwan. Patient eligibility was independent of the physician's decision to prescribe vortioxetine for an MDD episode. Vortioxetine was initiated on the first visit. Depression severity, cognitive function, work productivity, functioning and safety were evaluated over 3 months. RESULTS: Overall, 242 patients were analyzed. At baseline, 70.7% and 90.4% of patients had moderately severe-to-severe depression based on PHQ-9 (Patient Health Questionnaire-9) and TDQ (Taiwanese Depression Questionnaire), respectively. By Month 3, significant improvements from baseline in depression severity (mean [SD] changes in PHQ-9, TDQ and CGI-S [Clinical Global Impression-Severity]: -6.3 [7.3]; -13.2 [14.0]; -1.5 [1.3], respectively), cognitive function (mean [SD] change in PDQ-D: -8.0 [17.5]), functioning (mean [SD] change in SDS: -5.4 [7.6]), and presenteeism (38.9% from 56.3%), work productivity loss (40.9% from 58.7%) and activity impairment (43.2% from 61.0%) were observed (p < .001 for all). By month 3, patient-reported (PHQ-9) response and remission rates were 43.4% and 52.9%, respectively; physician-reported (CGI-S) response and remission rates were 29.0% and 31.6%, respectively. Vortioxetine was well-tolerated and no unexpected side effects were reported. CONCLUSIONS: Vortioxetine reduced depression severity and improved cognitive function, work productivity, and functioning in Taiwanese patients with MDD in the real-world setting. Vortioxetine was well-tolerated in this Taiwanese population.
Assuntos
Transtorno Depressivo Maior , Adulto , Antidepressivos/efeitos adversos , Ásia , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Método Duplo-Cego , Humanos , Estudos Prospectivos , Sulfetos/efeitos adversos , Vortioxetina/uso terapêuticoRESUMO
El montelukast se utiliza ampliamente en el tratamiento de sibilancias recurrentes y/o asma. Están descritas numerosas reacciones adversas medicamentosas (RAM) en niños relacionadas con montelukast; se destacan las neuropsiquiátricas. Realizamos un estudio observacional, retrospectivo, descriptivo, sobre RAM relacionadas con montelukast. Entre enero de 2012 y diciembre de 2017, en la Unidad de Neumonología Pediátrica se trataron con Montelukast 348 pacientes; de ellos, 20 presentaron RAM. Los síntomas más frecuentes fueron insomnio (n = 7), hiperactividad (n = 4), pesadillas (n = 3), dolor abdominal (n = 2) y parestesias en extremidades (n = 2). Se presentaron desde días hasta meses tras iniciar el tratamiento, y desaparecieron tras su suspensión. Se destacan dos pacientes con parestesias en extremidades, síntoma no descrito antes en niños. El 5,7 % de los pacientes tratados con montelukast presentaron RAM que requirieron suspender el tratamiento. Los trastornos del sueño fueron los más frecuentes.
Montelukast is widely used in recurrent wheezing and/or asthma treatment. Several adverse drug reactions (ADRs) have been described in children related to montelukast. Neuropsychiatric reactions are one of the most important. We designed an observational, retrospective, descriptive study on ADRs related to montelukast in the Pediatric Pulmonology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain. Between January 2012 and December 2017, in the Pediatric Pulmonology Unit, 348 patients were treated with Montelukast; of them, 20 presented RAM. The main symptoms described were insomnia (n = 7), hyperactivity (n = 4), nightmares (n = 3), abdominal pain (n = 2) and paraesthesia in extremities (n = 2). They appeared from the first days to months after the start of treatment and disappeared after stopping it. Two patients presented limb paresthesia, not described previously in children. The 5.7 % of our patients treated with montelukast had ADRs that required treatment discontinuation. Sleep disorders were the most frequent.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Quinolinas/efeitos adversos , Sulfetos/efeitos adversos , Antiasmáticos/efeitos adversos , Antagonistas de Leucotrienos/efeitos adversos , Ciclopropanos/efeitos adversos , Acetatos/efeitos adversos , Asma/tratamento farmacológico , Transtornos do Sono-Vigília/induzido quimicamente , Estudos RetrospectivosRESUMO
PURPOSE: Investigating the efficacy and safety of rupatadine (RUP) versus montelukast (MON) as adjuvant therapy for patients with rheumatoid arthritis (RA). METHODS: From December 2018 to December 2019, 75 patients with active RA were enrolled in this randomized double-blind placebo-controlled study. The patients were randomized into three groups (n = 25 in each group); methotrexate (MTX) group which received MTX 15-25 mg/week plus placebo tablet once daily; MTX/RUP group which received MTX plus RUP 10 mg once daily; and MTX/MON group which received MTX plus MON 10 mg once daily. The treatment duration was 3 months. At baseline and 3 months after treatment, blood samples were collected for the biochemical analysis of high-sensitivity C-reactive protein (hs-CRP), interleukins 8 and 17 (IL-8, IL-17), E-selectin, and clusterin (CLU) levels. Clinical and functional assessments using Disease Activity Score-CRP (DAS28-CRP) and Multidimensional Health Assessment Questionnaire (MDHAQ) were performed. RESULTS: Both RUP and MON produced clinical and functional improvements which were translated by significant improvements in DAS28-CRP score and MDHAQ. Rupatadine significantly reduced all measured parameters (P < 0.05) except for IL-17 and CLU. Montelukast significantly decreased all measured variables (P < 0.05) except for E-selectin. Interleukin-8 was positively correlated with IL-17 and CLU, while hs-CRP was positively correlated with E-selectin and body mass index (BMI). Both drugs were well tolerated; somnolence was the common side effect for RUP. No neuropsychiatric events were reported with MON. CONCLUSION: Rupatadine or montelukast may serve as a potential adjuvant therapy for patients with rheumatoid arthritis secondary to the preliminary evidence of efficacy and safety. ClinicalTrials.gov identifier NCT03770923, December 10, 2018.
Assuntos
Acetatos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Ciclopropanos/uso terapêutico , Ciproeptadina/análogos & derivados , Antagonistas dos Receptores Histamínicos/uso terapêutico , Imunossupressores/uso terapêutico , Antagonistas de Leucotrienos/uso terapêutico , Quinolinas/uso terapêutico , Sulfetos/uso terapêutico , Acetatos/administração & dosagem , Acetatos/efeitos adversos , Adulto , Índice de Massa Corporal , Proteína C-Reativa/efeitos dos fármacos , Clusterina/efeitos dos fármacos , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Ciproeptadina/administração & dosagem , Ciproeptadina/efeitos adversos , Ciproeptadina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Selectina E/efeitos dos fármacos , Egito , Feminino , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Interleucinas/metabolismo , Antagonistas de Leucotrienos/administração & dosagem , Antagonistas de Leucotrienos/efeitos adversos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Sulfetos/administração & dosagem , Sulfetos/efeitos adversosRESUMO
BACKGROUND: Cough variant asthma (CVA) is classified as a distinct form of asthma. As the primary or only symptom, cough is the leading cause for the most prevalent chronic cough among kids. The American College of Clinical Pharmacy, British Thoracic Society, and Chinese guidelines established for diagnosing and treating chronic cough in kids recommend inhaled corticosteroids, combined with leukotriene receptor antagonists when necessary. METHODS: We will conduct a comprehensive search in major databases using keywords to find studies related to the analysis of montelukast sodium and budesonide for treating CVA in kids. Two reviewers will independently assess the quality of the selected research articles and perform data extraction. Next, we will use the RevMan software (version: 5.3) to conduct the statistical analysis of the present study. RESULTS: This study will assess the efficacy and safeness of using montelukast sodium and budesonide to treat kids with CVA by pooling the results of individual studies. CONCLUSION: Our findings will provide vigorous evidence to judge whether montelukast sodium and budesonide therapy is an efficient form of therapy for CVA patients. ETHICS AND DISSEMINATION: Ethics approval is not needed for the present meta-analysis. OSF REGISTRATION NUMBER: May 17, 2021.osf.io/cuvjz (https://osf.io/cuvjz/).
Assuntos
Asma/tratamento farmacológico , Tosse/tratamento farmacológico , Glucocorticoides/administração & dosagem , Antagonistas de Leucotrienos/administração & dosagem , Acetatos/administração & dosagem , Acetatos/efeitos adversos , Administração por Inalação , Asma/diagnóstico , Asma/imunologia , Budesonida/administração & dosagem , Budesonida/efeitos adversos , Criança , Doença Crônica/tratamento farmacológico , Tosse/diagnóstico , Tosse/imunologia , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Glucocorticoides/efeitos adversos , Humanos , Antagonistas de Leucotrienos/efeitos adversos , Metanálise como Assunto , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfetos/administração & dosagem , Sulfetos/efeitos adversos , Revisões Sistemáticas como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Pediatric obstructive sleep apnea syndrome (OSAS) is significant public concern. Clinical practice indicates that montelukast has certain therapeutic advantages, while there is a lack of evidence-based medicine support. The aim of this study is to synthesize related data to explore efficacy and safety of montelukast for pediatric OSAS. METHODS: Data in Pubmed, EMBASE, CENTRAL, CBM, CNKI, WanFang, VIP databases were comprehensively searched. All the randomized controlled trials (RCTs) in OSAS children were identified, in which the effects of montelukast on a range of outcomes were compared. The search had a deadline of January 1, 2020. Two investigators independently conducted data extraction and assessed the literature quality of the included studies. The Revman5.3 software was used for meta-analysis of the included literature. RESULTS: The efficacy and safety of montelukast in the treatment of pediatric OSAS were evaluated in terms of apnea hypopnea index (AHI), the Pittsburgh Sleep Quality Index, the Epworth Sleep Scale (ESS), neck circumference, important index in Polysomnography: sleep efficiency, desaturation index, total sleep time. CONCLUSIONS: This study provides reliable evidence-based support for the clinical application of montelukast in the treatment of pediatric OSAS. PROSPERO REGISTRATION NUMBER: CRD42020146940.
Assuntos
Acetatos/uso terapêutico , Protocolos Clínicos , Ciclopropanos/uso terapêutico , Quinolinas/uso terapêutico , Apneia Obstrutiva do Sono/tratamento farmacológico , Sulfetos/uso terapêutico , Acetatos/efeitos adversos , Antiasmáticos/efeitos adversos , Antiasmáticos/uso terapêutico , Criança , Ciclopropanos/efeitos adversos , Humanos , Metanálise como Assunto , Polissonografia/métodos , Quinolinas/efeitos adversos , Apneia Obstrutiva do Sono/fisiopatologia , Sulfetos/efeitos adversos , Revisões Sistemáticas como AssuntoRESUMO
Acute asthma exacerbations are primarily due to airway inflammation and remain one of the most frequent reasons for childhood hospitalizations. Although systemic corticosteroids remain the mainstay of therapy because of their anti-inflammatory properties, not all inflammatory pathways are responsive to systemic corticosteroids, necessitating hospital admission for further management. Cysteinyl leukotrienes (LTs) are proinflammatory mediators that play an important role in systemic corticosteroids non-responsiveness. Montelukast is a potent LT-receptor antagonist, and an intravenous preparation caused rapid, sustained improvement of acute asthma exacerbations in adults. We hypothesized that a 30-mg dose of oral montelukast achieves peak plasma concentrations (Cmax ), comparable to the intravenous preparation (1700 ng/mL) and would be well tolerated in 15 children aged 5 to 12 years with acute asthma exacerbations. After administration of montelukast chewable tablets, blood samples were collected at 0, 15, 30, 45, 60, 120, 180, and 240 minutes. Plasma was separated and frozen at -80°C until analysis for montelukast concentration using liquid chromatography- tandem mass spectrometry. Median time to Cmax (tmax ) was 3.0 hours. Six participants (40%) achieved Cmax of 1700 ng/mL or higher. However, there was high interindividual variability in peak plasma concentration (median Cmax of 1378 ng/mL; range, 16-4895 ng/mL). No participant had side effects or adverse events. Plasma concentrations from this pilot study support the design of a weight-based dose-finding study aimed at selecting an optimal dose for future clinical trials to assess the efficacy of high-dose oral montelukast in children with moderate to severe asthma exacerbations.
Assuntos
Acetatos/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Ciclopropanos/administração & dosagem , Antagonistas de Leucotrienos/administração & dosagem , Quinolinas/administração & dosagem , Sulfetos/administração & dosagem , Acetatos/efeitos adversos , Acetatos/farmacocinética , Administração Oral , Antiasmáticos/efeitos adversos , Antiasmáticos/farmacocinética , Asma/fisiopatologia , Peso Corporal , Criança , Pré-Escolar , Cromatografia Líquida , Ciclopropanos/efeitos adversos , Ciclopropanos/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Humanos , Antagonistas de Leucotrienos/efeitos adversos , Antagonistas de Leucotrienos/farmacocinética , Masculino , Gravidade do Paciente , Projetos Piloto , Estudos Prospectivos , Quinolinas/efeitos adversos , Quinolinas/farmacocinética , Sulfetos/efeitos adversos , Sulfetos/farmacocinética , Comprimidos , Espectrometria de Massas em Tandem , Fatores de TempoRESUMO
BACKGROUND: Vortioxetine is approved for the treatment of Major Depressive Disorder (MDD). However, the safety of this drug in a large group of populations is still unclear. Thus, we have tried to analyze the risk profile of vortioxetine. MATERIAL AND METHODS: The data related to the risk profile of vortioxetine has been extracted from Pub-Med from January 2014 to May 2019. The adverse drug reactions (ADRs) have been categorized into listed and unlisted categories as per the Summary of product characteristics (SmPC) of the innovator. Further, unlisted ADRs have been analyzed as per Naranjo Scale. RESULTS: Galactorrhea, hyperprolactinemia, glycolimia, exacerbation of anxiety, weight gain, edema, excessive itching, petechiae, and ecchymoses have been observed with the use of vortioxetine and falls under the unlisted category. Further, the causality assessment results have shown a probable relation between vortioxetine and galactorrhea, hyperprolactinemia, edema, excessive itching, ecchymoses, and petechiae. Weight gain, glycolimia and exacerbation of anxiety have a possible relationship with vortioxetine. The common ADRs observed with the use of vortioxetine are nausea, diarrhea, constipation, vomiting, pruritus, including pruritus generalized, abnormal dreams, and dizziness. CONCLUSION: In conclusion, more data is required to establish a strong relationship between vortioxetine and reported unlisted ADRs.