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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 -
Drugs Aug 1998Montelukast is a selective antagonist of the leukotriene D4 (LTD4) receptor. In patients with asthma, montelukast 5 to 250 mg/day attenuated LTD4-induced... (Clinical Trial)
Clinical Trial Randomized Controlled Trial Review
Montelukast is a selective antagonist of the leukotriene D4 (LTD4) receptor. In patients with asthma, montelukast 5 to 250 mg/day attenuated LTD4-induced bronchoconstriction and, at a dosage of 10 mg, significantly reduced early and late airway response to allergen (dust mite extract) relative to placebo. In studies evaluating the effects of various dosages of montelukast on exercise-induced bronchoconstriction the optimal dose of the drug was found to be 10 mg. Montelukast 10 mg/day controlled asthma significantly more effectively than placebo in a 3-month randomised double-blind study. In a 9-month open extension of this trial, during which patients were randomised to treatment with montelukast 10 mg/day or beclomethasone (approximately 400 micrograms/day), daytime symptom score and beta-agonist use decreased to a similar extent in each group. In a further study, treatment with montelukast 10 mg/day permitted clinically significant tapering of corticosteroid dosage in patients with stable asthma. Montelukast (5 mg/day) has also demonstrated efficacy in childhood asthma. The tolerability profile of montelukast was similar to that of placebo in placebo-controlled clinical trials in adults and children; the most common adverse event was headache.
Topics: Acetates; Adult; Anti-Asthmatic Agents; Asthma; Child; Cyclopropanes; Drug Tolerance; Humans; Quinolines; Sulfides
PubMed: 9711449
DOI: 10.2165/00003495-199856020-00010 -
Expert Opinion on Pharmacotherapy Apr 2023Montelukast is a leukotriene inhibitor that is widely used to treat chronic asthma and allergic rhinitis. The drug interferes with molecular signaling pathways produced... (Review)
Review
INTRODUCTION
Montelukast is a leukotriene inhibitor that is widely used to treat chronic asthma and allergic rhinitis. The drug interferes with molecular signaling pathways produced by leukotrienes in a variety of cells and tissues throughout the human body that lead to tightening of airway muscles, production of aberrant pulmonary fluid (airway edema), and in some cases, pulmonary inflammation.
AREAS COVERED
Montelukast has also been noted to have anti-inflammatory properties, suggesting it may have a role in the treatment of coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has been noted to induce misfiring of the immune system in some patients. A literature search of PubMed was performed to identify all relevant studies of montelukast and SARS-CoV-2 through 27 January 2023.
EXPERT OPINION
Montelukast has been the subject of small studies of SARS-CoV-2 and will be included in a large, randomized, double-blind, placebo-controlled study of outpatients with COVID-19 sponsored by the United States National Institutes of Health known as Accelerating COVID-19 Therapeutic Interventions and Vaccines-6. This paper reviews what is known about montelukast, an inexpensive, well-tolerated, and widely available medication, and examines the rationale for using this drug to potentially treat patients with COVID-19.
Topics: Humans; COVID-19; Leukotriene Antagonists; SARS-CoV-2; Asthma; Acetates; Quinolines; Cyclopropanes; Sulfides; Double-Blind Method; Randomized Controlled Trials as Topic
PubMed: 36927284
DOI: 10.1080/14656566.2023.2192866 -
Expert Opinion on Drug Safety May 2009Suicide is a serious public health problem. Prevention of suicide depends to a great degree on identification and mitigation of its risk factors. Allergy has been... (Review)
Review
BACKGROUND
Suicide is a serious public health problem. Prevention of suicide depends to a great degree on identification and mitigation of its risk factors. Allergy has been associated with mood and anxiety disorders, risk factors for suicidality. Antiallergic medication could modulate or mediate these predictive associations. Recently, the FDA issued a warning raising concerns about the suicidality potential of montelukast and other leukotriene (LT) antagonists.
OBJECTIVE
The purpose of this review is to integrate the emerging interpretations of the link between suicidality, suicide risk factors, allergy and treatment of allergy in particular, with LT antagonists.
METHODS
We reviewed the available reports on the possible relationships between montelukast, allergy, suicide, suicidality and suicide risk factors. We also present the positions of the FDA, manufacturer, and national organizations of allergists and immunologists on the possible role of montelukast in suicidality.
CONCLUSION
At present, there is insufficient data to prove that there is a link between montelukast and suicidality. Inquiring about mood changes and suicidal ideation should be integrated in general medical practice.
Topics: Acetates; Cyclopropanes; Humans; Hypersensitivity; Quinolines; Risk Factors; Suicide; Sulfides; Suicide Prevention
PubMed: 19505261
DOI: 10.1517/14740330902932688 -
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 -
Drugs 2000The tolerability of a medication, especially in children with asthma, is linked to a number of key factors. These include clinical effectiveness, adverse effects,... (Review)
Review
The tolerability of a medication, especially in children with asthma, is linked to a number of key factors. These include clinical effectiveness, adverse effects, frequency of drug regimen, ease and route of administration. and taste. Montelukast is unusual in that, in most countries, a licence for children aged > or =6 years was granted at the same time as the adult licence. This is related to a variety of evidence. which includes pharmacological and adult studies suggesting the specificity and safety of the drug at many times the licensed dose, and a tolerability profile similar to that with placebo or inhaled corticosteroids in both adult and paediatric studies. The most common adverse effects in paediatric studies were headache, asthma and upper respiratory tract infection at rates not statistically significantly different from those with placebo. Up to July 1999, more than 2 million patients worldwide have received montelukast, of whom nearly 220,000 have received the paediatric formulation. In the UK, one prescribing database suggests that, of children who commenced montelukast therapy, less than 25% discontinued the drug. This implies that montelukast is effective and well tolerated in most children. Adverse effect monitoring by regulatory bodies has revealed little that would not be expected on the basis of the results of clinical trials. Montelukast has been associated with Churg-Strauss syndrome in a very small number of adults. In most. the syndrome was associated with corticosteroid withdrawal, which may have unmasked the condition. Churg-Strauss syndrome has not been reported in children. Its clinical effectiveness, lack of major adverse effects, oral route of administration, palatability and the once-daily regimen combine to make montelukast a generally well tolerated medication in children.
Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Asthma; Child; Churg-Strauss Syndrome; Controlled Clinical Trials as Topic; Cyclopropanes; Humans; Leukotriene Antagonists; Product Surveillance, Postmarketing; Quinolines; Sulfides
PubMed: 10741881
DOI: 10.2165/00003495-200059001-00006 -
The Clinical Respiratory Journal Oct 2023Montelukast is a highly selective and specific cysteinyl leukotriene receptor antagonist used in the treatment of asthma. Whether montelukast as adjuvant therapy can... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Montelukast is a highly selective and specific cysteinyl leukotriene receptor antagonist used in the treatment of asthma. Whether montelukast as adjuvant therapy can significantly and safely treat adults with cough variant asthma (CVA) remains inconclusive.
AIMS
This meta-analysis systematically evaluated the efficacy and safety of montelukast as an adjuvant treatment for adults with CVA.
MATERIALS AND METHODS
Randomized controlled trials (RCTs) on montelukast combined with inhaled corticosteroids (ICS) and long-acting β2 agonists (LABAs) to treat CVA in adults, from inception to March 6, 2023, were retrieved from the CNKI, Wanfang, VIP, CBM, PubMed, Embase, Cochrane Library, and Web of Science databases and Clinical Trials website. Review Manager (version 5.4) and Stata (version 15.0) were used to conduct the meta-analysis.
RESULTS
A total of 15 RCTs were ultimately included in the meta-analysis. It was established that montelukast as adjuvant therapy raised the total effective rate (RR = 1.20, 95% confidence interval [CI] [1.13, 1.27], P < 0.01) and improved the FEV1% (SMD = 0.91, 95% CI [0.40, 1.41], P < 0.01), PEF% (SMD = 0.63, 95% CI [0.38, 0.88], P < 0.01), FEV1 (SMD = 1.15, 95% CI [0.53, 1.77], P < 0.01), PEF (SMD = 0.64, 95% CI [0.42, 0.86], P < 0.01), and FEV1/FVC% (SMD = 0.76, 95% CI [0.51, 1.01], P < 0.01) and reduced the recurrence rate (RR = 0.28, 95% CI [0.15, 0.53], P < 0.01). The incidence of adverse reactions was higher in the montelukast auxiliary group compared to the control group but with no statistical difference (RR = 1.32, 95% CI [0.89, 1.96], P = 0.17).
CONCLUSION
Existing evidence indicated that the use of montelukast as an adjuvant therapy had therapeutic efficacy superior to ICS + LABA alone for the treatment of adult patients with CVA. However, further research is needed, especially a combination of high-quality long-term prospective studies and carefully designed RCTs.
Topics: Adult; Humans; Anti-Asthmatic Agents; Cough; Adrenergic beta-Agonists; Drug Therapy, Combination; Asthma; Adrenal Cortex Hormones
PubMed: 37218346
DOI: 10.1111/crj.13629 -
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 -
The Journal of Asthma : Official... Apr 2022Several therapeutic agents have been assessed for the treatment of COVID-19, but few approaches have been proven efficacious. Because leukotriene receptor antagonists,...
OBJECTIVE
Several therapeutic agents have been assessed for the treatment of COVID-19, but few approaches have been proven efficacious. Because leukotriene receptor antagonists, such as montelukast have been shown to reduce both cytokine release and lung inflammation in preclinical models of viral influenza and acute respiratory distress syndrome, we hypothesized that therapy with montelukast could be used to treat COVID-19. The objective of this study was to determine if montelukast treatment would reduce the rate of clinical deterioration as measured by the COVID-19 Ordinal Scale.
METHODS
We performed a retrospective analysis of COVID-19 confirmed hospitalized patients treated with or without montelukast. We used "clinical deterioration" as the primary endpoint, a binary outcome defined as any increase in the Ordinal Scale value from Day 1 to Day 3 of the hospital stay, as these data were uniformly available for all admitted patients before hospital discharge. Rates of clinical deterioration between the montelukast and non-montelukast groups were compared using the Fisher's exact test. Univariate logistic regression was also used to assess the association between montelukast use and clinical deterioration. A total of 92 patients were analyzed, 30 who received montelukast at the discretion of the treating physician and 62 patients who did not receive montelukast.
RESULTS
Patients receiving montelukast experienced significantly fewer events of clinical deterioration compared with patients not receiving montelukast (10% vs 32%, = 0.022). Our findings suggest that montelukast associates with a reduction in clinical deterioration for COVID-19 confirmed patients as measured on the COVID-19 Ordinal Scale.
CONCLUSIONS
Hospitalized COVID-19 patients treated with montelukast had fewer events of clinical deterioration, indicating that this treatment may have clinical activity. While this retrospective study highlights a potential pathway for COVID-19 treatment, this hypothesis requires further study by prospective studies.
Topics: Acetates; Asthma; Clinical Deterioration; Cyclopropanes; Humans; Leukotriene Antagonists; Prospective Studies; Quinolines; Retrospective Studies; SARS-CoV-2; Sulfides; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33577360
DOI: 10.1080/02770903.2021.1881967 -
The Annals of Pharmacotherapy May 2006To review clinical trial data to determine the benefits of using montelukast alone or as combination therapy in the treatment of urticaria. (Review)
Review
OBJECTIVE
To review clinical trial data to determine the benefits of using montelukast alone or as combination therapy in the treatment of urticaria.
DATA SOURCES
MEDLINE (1966-March 2006) and International Pharmaceutical Abstracts (1970-October 2005) were searched to find clinical trial publications that addressed the use of montelukast in urticaria.
DATA SYNTHESIS
Six clinical trials were identified. Montelukast was compared alone and as combination therapy with nonsedating histamine1-receptor antagonists to determine efficacy and safety. Patients had chronic or physical urticaria. The results were mixed. Some studies demonstrated that montelukast can decrease urticarial symptoms with minimal adverse effects, while others found no differences.
CONCLUSION
Large-scale, controlled trials are needed to determine which patients would likely benefit from treatment with montelukast.
Topics: Acetates; Clinical Trials as Topic; Cyclopropanes; Drug Therapy, Combination; Histamine H1 Antagonists, Non-Sedating; Humans; Leukotriene Antagonists; Quinolines; Sulfides; Urticaria
PubMed: 16670370
DOI: 10.1345/aph.1G006