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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... 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 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 -
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 -
Otolaryngology--head and Neck Surgery :... Feb 2023To develop an expert consensus statement regarding persistent pediatric obstructive sleep apnea (OSA) focused on quality improvement and clarification of controversies....
OBJECTIVE
To develop an expert consensus statement regarding persistent pediatric obstructive sleep apnea (OSA) focused on quality improvement and clarification of controversies. Persistent OSA was defined as OSA after adenotonsillectomy or OSA after tonsillectomy when adenoids are not enlarged.
METHODS
An expert panel of clinicians, nominated by stakeholder organizations, used the published consensus statement methodology from the American Academy of Otolaryngology-Head and Neck Surgery to develop statements for a target population of children aged 2-18 years. A medical librarian systematically searched the literature used as a basis for the clinical statements. A modified Delphi method was used to distill expert opinion and compose statements that met a standardized definition of consensus. Duplicate statements were combined prior to the final Delphi survey.
RESULTS
After 3 iterative Delphi surveys, 34 statements met the criteria for consensus, while 18 statements did not. The clinical statements were grouped into 7 categories: general, patient assessment, management of patients with obesity, medical management, drug-induced sleep endoscopy, surgical management, and postoperative care.
CONCLUSION
The panel reached a consensus for 34 statements related to the assessment, management and postoperative care of children with persistent OSA. These statements can be used to establish care algorithms, improve clinical care, and identify areas that would benefit from future research.
Topics: Child; Humans; Adenoidectomy; Endoscopy; Postoperative Care; Sleep Apnea, Obstructive; Tonsillectomy
PubMed: 36757810
DOI: 10.1002/ohn.159