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health and well-being, being associated with disruption of sleeping patterns(4), cognitive and performance impairment(5,6) and decrease in quality of life(7) and work and school performance(5,8). In addition, AR may also be associated with higher risk for psychiatric disease - mental illness was found to be associated with several chronic diseases, including chronic respiratory diseases. An association between allergic disorders (asthma, rhinitis and dermatitis) and mental illness has been identified, especially in mood disorders such as depression and anxiety(9,10). Furthermore, depressive symptoms have also been correlated with seasonality and severity of allergy(11). Asthma is the allergic disorder for which there have been more studies establishing an association with the development of mental illness. In fact, a previous systematic review 361 Anxiety and depression in allergic rhinitis has found that asthmatic patients have a risk 2.1 times higher of developing depression and a risk 1.8 times higher of developing anxiety when compared to those without asthma(12). Although it is possible that a similar association with mood disorders can also be found in AR, such association has not been systematically reviewed in a fully dedicated study to this research question. The aim of this study is to systematically review the literature to assess and quantify the association between AR and depression and anxiety. In addition, we aimed to identify variables potentially explaining heterogeneity across studies. Materials and methods Eligibility criteria and search strategy This review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement and with the Cochrane Handbook for Systematic Reviews(13,14). We included observational studies comparing patients with diagnosed AR versus those without AR on the frequency of depression and/or anxiety. Case reports, reviews and editorials were excluded. Our search was performed in three electronic databases – PubMed, Web of Science and Scopus –, in March 2020. Research on electronic databases was complemented with manual review of the references in the included primary studies. No date or language restrictions were applied. Study selection and data extraction After duplicates removal, two authors (JR and FFP) independently screened all titles and abstracts of the studies obtained from database searches. Subsequently, the full texts of selected studies were retrieved and independently read by two authors (JR and FFP), who extracted data on the year of publication, country of study, study design, average age, percentage of female subjects, frequency of asthma and atopic dermatitis, percentage of urban dwellers, AR definition and method of assessment, depression/anxiety definition and method of assessment, number of subjects with and without AR, frequency of depression and anxiety in each group and adjusted effect size measures. Countries where the study was performed were grouped into three regions - Europe, USA and Far East. Concerning AR assessment, studies were classified into those in which AR 1) was clinically diagnosed when the study was being performed, 2) had been previously registered by a healthcare professional (i.e., information on AR was obtained by consulting patients’ clinical files), or 3) was simply reported by the patient. We also classified primary studies according to the method of outcome assessment (either depression or anxiety), into those in which 1) a previous diagnosis had been registered by a healthcare professional (i.e., information on depression/anxiety was obtained by consulting participants’ clinical files); 2) validated questionnaires were applied, or 3) symptoms or a previous diagnosis had simply been reported by the patient without
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