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JAMA Network Open May 2022The evidence base for the association between montelukast and adverse neuropsychiatric outcomes is mixed and inconclusive. Several methodological limitations have been...
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 154 946 patients, of whom 77 473 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 72 490 patients with asthma (44 726 [61.7%] women; mean [SD] age at index prescription, 35 [15] years) and 82 456 patients with allergic rhinitis (54 172 [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.
Topics: Acetates; Adolescent; Adult; Anti-Asthmatic Agents; Asthma; Cohort Studies; Cyclopropanes; Female; Humans; Male; Mental Disorders; Middle Aged; Quinolines; Rhinitis, Allergic; Sulfides; Young Adult
PubMed: 35608857
DOI: 10.1001/jamanetworkopen.2022.13643 -
European Respiratory Review : An... Dec 2023We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other treatments or placebo.
METHODS
Protocol registration CRD42020216098 (www.crd.york.ac.uk/PROSPERO). MEDLINE and Embase databases were used to conduct the search. Two authors independently selected studies and extracted data, and a third reviewer resolved discrepancies. Meta-analyses were constructed to estimate the standardised mean difference (SMD) using a random-effects model.
RESULTS
Out of 3937 articles identified, 49 studies met the inclusion criteria, mostly randomised clinical trials (sample sizes: 21-689 patients). The SMD of change pooled estimators for the global, mental and physical domains of health-related quality of life were not statistically significant. For daytime and night-time symptoms scores, the SMD (95% CI) was in favour of inhaled corticosteroids (-0.12, -0.20- -0.05 and -0.23, -0.41- -0.06, respectively). The pooled estimator for global asthma symptoms was better for montelukast when compared with placebo (0.90, 0.44-1.36).
CONCLUSIONS
The synthesis of the available evidence suggests that, in children and adolescents, montelukast was effective in controlling asthma symptoms when compared with placebo, but inhaled corticosteroids were superior in controlling symptoms, especially at night-time. These findings of our systematic review concur with current guidelines for asthma treatment.
Topics: Adolescent; Humans; Child; Quality of Life; Asthma; Rhinitis, Allergic; Adrenal Cortex Hormones
PubMed: 37852659
DOI: 10.1183/16000617.0124-2023 -
Indian Journal of Pharmacology 2016Allergic rhinitis (AR) is a global health problem. Almost 10%-25% of population worldwide is affected by AR. Oral/intranasal H1-antihistamine, decongestants, leukotriene... (Comparative Study)
Comparative Study Randomized Controlled Trial
Comparison of efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine in patients of allergic rhinitis: A randomized, double-blind clinical trial.
OBJECTIVES
Allergic rhinitis (AR) is a global health problem. Almost 10%-25% of population worldwide is affected by AR. Oral/intranasal H1-antihistamine, decongestants, leukotriene receptor antagonists, and intranasal corticosteroids are the pillars in the management of AR. The combination therapy of montelukast with antihistaminic provides enhancing and complimentary effects, thereby reducing the symptoms effectively, but there are scanty data regarding the comparisons of combinations. Therefore, we aimed to compare the efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine combination in patients of AR.
MATERIALS AND METHODS
Seventy patients with AR participated in a prospective, randomized, double-blind, parallel, active-controlled, comparative 4-week trial. The patients between the age group of 18-65 years of either gender having moderate-severe intermittent or mild persistent AR were included in the study. The study inclusion criteria required the patients with total nasal symptom score (TNSS) of 5 or higher. The patients were randomly divided into two treatment groups with montelukast-levocetirizine (10 mg and 5 mg) in one group and montelukast-fexofenadine (10 mg and 120 mg) in another group. TNSS parameter was the main effectiveness parameter.
RESULTS
Evaluation of TNSS revealed significant difference ( < 0.05) when compared from baseline to 4 week in both groups. The mean change of TNSS, i.e., 9.46 was significant ( < 0.05) in montelukast-fexofenadine group. The cost-effectiveness ratio was less in montelukast-levocetirizine group than in montelukast-fexofenadine group.
CONCLUSION
The decrease in TNSS was more in montelukast-fexofenadine group, but the cost-effectiveness is more with montelukast-levocetirizine combination.
Topics: Acetates; Anti-Allergic Agents; Anti-Asthmatic Agents; Cetirizine; Cost-Benefit Analysis; Cyclopropanes; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Prospective Studies; Quinolines; Rhinitis, Allergic; Sulfides; Terfenadine; Treatment Outcome
PubMed: 28066101
DOI: 10.4103/0253-7613.194854 -
Biology of Blood and Marrow... Apr 2016Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled...
Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P < .001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM.
Topics: Acetates; Adult; Aged; Anti-Inflammatory Agents; Azithromycin; Bronchiolitis Obliterans; Cyclopropanes; Disease Progression; Fluticasone; Forced Expiratory Volume; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Lung; Male; Middle Aged; Quality of Life; Quinolines; Sulfides; Survival Analysis; Transplantation, Homologous; Treatment Outcome
PubMed: 26475726
DOI: 10.1016/j.bbmt.2015.10.009 -
Respiratory Research Oct 2022Whether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), and that... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Whether cysteinyl-leukotriene receptor antagonists (LTRAs) have a similar antitussive effect to inhaled corticosteroids and long-acting β2-agonist (ICS/LABA), and that LTRA plus ICS/LABA is superior to LTRAs alone or ICS/LABA alone in treating cough variant asthma (CVA) remain unclear. This study aimed to investigate and compare the efficacy of montelukast alone, budesonide/formoterol alone and the combination of both in the treatment of CVA.
METHODS
Ninety-nine CVA patients were assigned randomly in a 1:1:1 ratio to receive montelukast (M group: 10 mg, once daily), budesonide/formoterol (BF group: 160/4.5 μg, one puff, twice daily), or montelukast plus budesonide/formoterol (MBF group) for 8 weeks. The primary outcomes were changes in the cough visual analogue scale (VAS) score, daytime cough symptom score (CSS) and night-time CSS, and the secondary outcomes comprised changes in cough reflex sensitivity (CRS), the percentage of sputum eosinophils (sputum Eos%) and fractional exhaled nitric oxide (FeNO). CRS was presented with the lowest concentration of capsaicin that induced at least 5 coughs (C5). The repeated measure was used in data analysis.
RESULTS
The median cough VAS score (median from 6.0 to 2.0 in the M group, 5.0 to 1.0 in the BF group and 6.0 to 1.0 in the MBF group, all p < 0.001), daytime CSS (all p < 0.01) and night-time CSS (all p < 0.001) decreased significantly in all three groups after treatment for 8 weeks. Meanwhile, the LogC5 and sputum Eos% improved significantly in all three groups after 8 weeks treatment (all p < 0.05). No significant differences were found in the changes of the VAS score, daytime and night-time CSSs, LogC5 and sputum Eos% among the three groups from baseline to week 8 (all p > 0.05). The BF and MBF groups also showed significant decreases in FeNO after 8 weeks treatment (p = 0.001 and p = 0.008, respectively), while no significant change was found in the M group (p = 0.457). Treatment with MBF for 8 weeks significantly improved the FEV/FVC as well as the MMEF% pred and decreased the blood Eos% (all p < 0.05).
CONCLUSIONS
Montelukast alone, budesonide/formoterol alone and a combination of both were effective in improving cough symptom, decreasing cough reflex sensitivity and alleviating eosinophilic airway inflammation in patients with CVA, and the antitussive effect and anti-eosinophilic airway inflammation were similar. Trial registration ClinicalTrials.gov, number NCT01404013.
Topics: Acetates; Administration, Inhalation; Adrenal Cortex Hormones; Antitussive Agents; Asthma; Budesonide; Budesonide, Formoterol Fumarate Drug Combination; Capsaicin; Cough; Cyclopropanes; Formoterol Fumarate; Humans; Inflammation; Leukotriene Antagonists; Quinolines; Sulfides
PubMed: 36217131
DOI: 10.1186/s12931-022-02114-6 -
European Respiratory Review : An... Sep 2023The United States Food and Drug Administration issued a black box warning on the mental health adverse effects of montelukast in 2020. Age-related effects on the risk of... (Review)
Review
BACKGROUND
The United States Food and Drug Administration issued a black box warning on the mental health adverse effects of montelukast in 2020. Age-related effects on the risk of developing specific neuropsychiatric events in montelukast users remain largely unknown.
OBJECTIVE
To describe the risk of neuropsychiatric events associated with montelukast in adults and children with asthma.
METHODS
A systematic search of all studies investigating neuropsychiatric events in montelukast users was performed in PubMed, the Cochrane Library and Embase from inception to 7 September 2022. Animal studies and conference abstracts were excluded.
RESULTS
59 studies (21 pharmacovigilance studies, four reviews from 172 randomised controlled trials, 20 observational studies, 10 case reports and four case series) evaluating neuropsychiatric events in patients with asthma on montelukast were reviewed. No significant association was shown between montelukast and suicide-related events in six of the observational studies. No association was found for depression as defined by the International Classification of Diseases 10 revision codes in three observational studies and a review of randomised clinical trials. However, findings from four studies using antidepressant prescriptions as the outcome identified significant associations. Consistent with nine pharmacovigilance studies, two large-scale observational studies revealed possible associations of montelukast with anxiety and sleeping disorders in adult patients with asthma, respectively. However, the results were not replicated in two observational studies on children.
CONCLUSION
Montelukast is not associated with suicide- and depression-related events in asthma patients. Older adults may be particularly susceptible to anxiety and sleeping disorders.
Topics: Child; Animals; Humans; Aged; Asthma; Acetates; Quinolines; Cyclopropanes; Anti-Asthmatic Agents
PubMed: 37758273
DOI: 10.1183/16000617.0079-2023 -
European Journal of Pediatrics Jul 2017There is conflicting evidence of the effectiveness of montelukast in preschool wheeze. A recent Cochrane review focused on its use in viral-induced wheeze; however, such... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
There is conflicting evidence of the effectiveness of montelukast in preschool wheeze. A recent Cochrane review focused on its use in viral-induced wheeze; however, such subgroups are unlikely to exist in real life and change with time, recently highlighted in an international consensus report. We have therefore sought to investigate the effectiveness of montelukast in all children with preschool wheeze (viral-induced and multiple-trigger wheeze). The PubMed, Cochrane Library, Ovid Medline and Ovid EMBASE were screened for randomised controlled trials (RCTs), examining the efficacy of montelukast compared with placebo in children with the recurrent preschool wheeze. The primary endpoint examined was frequency of wheezing episodes. Five trials containing 3960 patients with a preschool wheezing disorder were analysed. Meta-analyses of studies of intermittent montelukast showed no benefit in preventing episodes of wheeze (mean difference (MD) 0.07, 95% confidence interval (CI) -0.14 to 0.29; mean for montelukast 2.68 vs placebo 2.54 (p = 0.5)), reducing unscheduled medical attendances (MD -0.13, 95% CI -0.33 to 0.07; mean for montelukast 1.62 vs placebo 1.78 (p = 0.21)) and reducing oral corticosteroids (MD -0.06, 95% CI -0.16 to 0.02; mean for montelukast 0.35 vs placebo 0.36 (p = 0.25)). The pooled results of the continuous regimen showed no significant difference in the number of wheezing episodes between the montelukast and placebo groups (MD -0.40, 95% CI -1.00 to 0.19; mean for montelukast 2.05 vs placebo 2.37 (p = 0.18)).
CONCLUSIONS
This review highlights that the currently available evidence does not support the use of montelukast in preschool children with recurrent wheeze. We recommend further studies to investigate if a 'montelukast responder' phenotype exists, and how these can be easily identified in the clinical setting. What is Known: • Current guidelines recommend montelukast use in preschool children with recurrent wheeze. • A recent Cochrane review has found montelukast to be ineffective at reducing courses of oral corticosteroids for viral-induced wheeze. What is New: • This meta-analysis has examined all children with preschool wheeze and found that montelukast was not effective at preventing wheezing episodes or reducing unscheduled medical attendances. • A specific montelukast responder phenotype may exist, but such patients should be sought in larger multicentre RCTs.
Topics: Acetates; Anti-Asthmatic Agents; Child; Child, Preschool; Cyclopropanes; Humans; Infant; Models, Statistical; Quinolines; Recurrence; Respiratory Sounds; Respiratory Tract Diseases; Sulfides; Treatment Outcome
PubMed: 28567533
DOI: 10.1007/s00431-017-2936-6 -
Iranian Journal of Allergy, Asthma, and... Aug 2021Coronavirus disease 2019 (COVID-19) is an emerging worldwide issue, that has affected a large number of people around the world. So far, many studies have aimed to... (Review)
Review
Coronavirus disease 2019 (COVID-19) is an emerging worldwide issue, that has affected a large number of people around the world. So far, many studies have aimed to develop a therapeutic approach against COVID-19. Montelukast (MK) is a safe asthma controller drug, which is considered as a potential antiviral drug for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review has a systematic approach to investigate the reports on the use of MK as a part of treatment or a prophylactic agent in COVID-19. The search was conducted in PubMed, Web of Science, and Scopus databases and yielded 35 studies containing the influence of MK on SARS-CoV-2. Ultimately, MK appears to be worth being used as an adjuvant therapeutic and prophylactic drug against SARS-CoV-2. Nevertheless, more clinical trials are required to accurately investigate its effectiveness.
Topics: Acetates; Antiviral Agents; COVID-19; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; SARS-CoV-2; Sulfides; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34418892
DOI: No ID Found -
Pakistan Journal of Medical Sciences 2022To investigate the effects of Montelukast sodium combined with Budesonide aerosol on airway function and T lymphocytes in asthmatic children.
OBJECTIVES
To investigate the effects of Montelukast sodium combined with Budesonide aerosol on airway function and T lymphocytes in asthmatic children.
METHODS
The records of 86 pediatric asthma patients, treated in Huzhou Maternal and Child Health Hospital from February 2020 to March 2021, were studied retrospectively. Of them, 40 children received routine treatment + budesonide atomizer (Group-I), and 46 patients received routine treatment + budesonide atomizer + montelukast sodium (Group-II). The improvement in airway and lung function, and T-lymphocyte count in both groups after 3 months of corresponding treatment were analyzed.
RESULTS
After three months of treatment, expiratory flow rate (TEF) with the tidal volume of 25%, 50% and 75%, was significantly higher in Group-II than Group-I (P<0.05). CD8+ expression in Group-II was lower, and CD3+, CD4+ and CD4+/CD8+ were higher than those in Group-I (P<0.05). There was a significant difference in the levels of inflammatory factors between the two groups. The levels of IL-4, IL-5 and IFN-γ in Group-II were lower than those in Group-I(P<0.05).
CONCLUSIONS
In the clinical treatment of asthmatic children, in combination with routine treatment, budesonide atomizer and montelukast sodium can effectively promote the improvement of airway function, regulate T lymphocytes levels, reduce inflammatory reaction and improve the total clinical curative effect.
PubMed: 35799724
DOI: 10.12669/pjms.38.5.5749 -
Frontiers in Bioscience (Elite Edition) Jan 2017Respiratory symptoms at rest or during exercise may restrain the physical capabilities required for normal motor and psychosocial development in children. The most... (Review)
Review
Respiratory symptoms at rest or during exercise may restrain the physical capabilities required for normal motor and psychosocial development in children. The most frequent cause of exercise intolerance, apart from poor physical fitness, is exercise-induced bronchoconstriction (EIB), which may occur in some healthy children and in children with asthma. It is proposed that hyperventilation during exercise is associated with drying and cooling of airways, which can trigger a proinflammatory response. Several tests are used to confirm EIB, and the exercise-challenge test is the most common. Some nonpharmacologic therapies may induce airway refractoriness; warm-up exercise can result in the attenuation of EIB in more than half of the people with EIB. Prophylactic intermittent treatment with short-acting bronchodilators is the most commonly used treatment, but the conventional pharmacologic therapy for patients with uncontrolled asthma is the regular use of inhaled corticosteroids, with or without long-acting beta-agonists and montelukast. Therapy should result in optimal control of exercise-induced symptoms during habitual physical activity and also allow participation in sports activity in athletes.
Topics: Acetates; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Bronchoconstriction; Child; Cyclopropanes; Energy Metabolism; Exercise; Humans; Oxygen; Pulmonary Gas Exchange; Quinolines; Respiratory Hypersensitivity; Sulfides
PubMed: 27814586
DOI: 10.2741/e782