Question | |
Should oral H1-antihistamines vs. no treatment be used for the treatment of allergic rhinitis? | |
Population: | Patients with allergic rhinitis |
Intervention: | oral H1-antihistamines |
Comparison: | no treatment |
Main outcomes: | Nasal symptoms Ocular symptoms Quality of life Adverse events (any) Serious adverse events |
Setting: | |
Perspective: | Clinical recommendation – patient perspective |
Background: | Oral antihistamines are one of the mainstays of the treatment of allergic rhinitis and are widely available. |
Conflict of interests: | AWMF conflict of interest declaration and management policies were applied, the assessment performed by the AWMF with guidance and help from Juan Jose Yepes Nuñez. |
Assessment
ProblemIs the problem a priority? | ||
Judgement | Research evidence | Additional considerations |
Allergic rhinitis (AR) is a common condition affecting 18.1% of the population, and its symptoms can significantly reduce the quality of life and pose a high economic burden (mainly because of indirect costs related to lost school days and workdays). [Savoure] Studies of patients consulting general practitioners for AR reported that 18–48 % had symptoms that were not controlled by pharmacotherapy. [Bousquet, Bhattacharyya, Vandenplas] Despite the bothersome nature of symptoms, AR is often trivialized by the patient – only 45% seek medical advice or treatment for their condition, which results in under-treatment and poor control of symptoms. [Linneberg] Problems related to disease Economic burden A systematic review performed to estimate the financial burden of AR in European countries [Linneberg] suggests that the GP services bore the majority of the direct costs for AR. However, the majority of the overall cost burden correspond to indirect costs caused by high absenteeism and presenteeism. In the United States, annual costs for medications for rhinitis patients can be estimated at approximately $1.3 billion. In total, direct costs are estimated to be >$4.6 billion for rhinitis management, including treatment, allergy testing, clinical visits and hospital procedures. [Roland] Similar findings were found for Asia. An analysis of the indirect costs associated with insufficiently treated AR and urticaria patients revealed an annual burden of USD 105.4 billion. This translates to a cost ranging from USD 1,137 to USD 2,195 per patient due to absenteeism and presenteeism [ Kulthanan] Clinical burden The median prevalence of allergic rhinitis was found to be 18.1%, based on a dataset that included 310 reported prevalences. The prevalence of AR ranged from as low as 1.0% to as high as 54.5%.
These statistics indicate that AR is a relatively common condition affecting a significant portion of the population, with variations in prevalence observed across different regions or studies. [Savouré] References:
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Desirable EffectsHow substantial are the desirable anticipated effects? | ||
Judgement | Research evidence | Additional considerations |
Nasal symptoms In a systematic review with network meta-analysis performed by Vieira et al. [1], the improvement of nasal symptoms was assessed in patients under oral antihistamines (OAH) and compared with that registered in patients receiving placebo. For patients with seasonal allergic rhinitis, it was possible to meta-analytically pool the total nasal symptom score (TNSS; combination of four nasal symptoms and scale of 0-12) results of 37 randomised controlled trials (RCTs). Second-generation OAHs were associated with a significantly higher improvement in the TNSS when compared to placebo (mean difference=-0.74; 95%CI=-0.88;-0.60). OAHs displayed a 100% probability of resulting in a small improvement when compared to placebo. For patients with perennial allergic rhinitis, it was possible to meta-analytically pool the four symptom TNSS results of 11 RCTs. OAHs were associated with a significantly higher improvement in the TNSS when compared to placebo (mean difference=-0.61; 95%CI=-0.74; -0.47). OAHs displayed a 100% probability of resulting in a small improvement when compared to placebo. Subgroup considerations: Children and adolescents We identified one study assessing the four symptom TNSS in children (seasonal allergic rhinitis). Oral antihistamines (cetirizine) were associated with a higher improvement in the TNSS compared to placebo (mean difference=-1.59; 95%CI=-2.23;-0.95). Ocular symptoms In a systematic review with network meta-analysis performed by Vieira et al. [1], the improvement of ocular symptoms was assessed in patients under OAH and compared with that registered in patients receiving placebo. For patients with seasonal allergic rhinitis, it was possible to meta-analytically pool the total ocular symptom score (TOSS) results of 13 RCTs, considering three ocular symptoms and a scale of 0-9. OAHs were associated with a significantly higher improvement in the TOSS when compared to placebo (mean difference=-0.59; 95%CI=-0.77;-0.41). OAHs displayed a 91% probability of resulting in a meaningful (small) improvement when compared to placebo. Additionally, it was possible to meta-analytically pool the total ocular symptom score (TOSS) results of 9 RCTs, considering four ocular symptoms and a scale of 0-12. OAHs were associated with a significantly higher improvement in the TOSS when compared to placebo (mean difference=-0.68; 95%CI=-0.88;-0.47). For patients with perennial allergic rhinitis, no primary studies were identified allowing for the comparison between OAHs versus placebo on their effect on the TOSS. Subgroup considerations: Children and adolescents No RCTs were identified evaluating the three symptoms or four symptoms TOSS in children. Quality-of-life In a systematic review with network meta-analysis performed by Vieira et al. [1], the improvement of quality-of-life was assessed in patients under OAHs and compared with that registered in patients receiving placebo. For patients with seasonal allergic rhinitis, it was possible to meta-analytically pool the rhinocojunctivitis quality of life questionnaire (RQLQ; scale of 0-6) results of 22 RCTs. Second-generation OAHs were associated with a significant difference in RQLQ changes when compared to placebo (mean difference=-0.27; 95%CI=-0.32;-0.22), while for first-generation OAHs the difference was not significant (mean difference=-0.14; 95%CI=-0.62;0.34). However, only a first-generation OAH (chlorpheniramine) was assessed by a single RCT. (OAHs displayed a 87% probability of resulting in a meaningful (small) improvement when compared to placebo. For patients with perennial allergic rhinitis, it was possible to meta-analytically pool the RQLQ results of 6 RCTs. OAHs were associated with a significant difference in RQLQ changes when compared to placebo (mean difference=-0.37; 95%CI=-0.47;-0.26). OAHs displayed a 78% probability of resulting in a meaningful (small) improvement when compared to placebo. Subgroup considerations: Children and adolescents We identified one study assessing the RQLQ in children with seasonal allergic rhinitis. Oral antihistamines (levocetirizine) were associated with a difference of 0.04 points in RQLQ change (no further information was provided). We identified four studies assessing the RQLQ in children with perennial allergic rhinitis. Oral antihistamines were associated with a higher improvement in RQLQ compared to placebo (mean difference=-0.83; 95%CI=-1.33;-0.32). Reference: 1. Vieira RJ, Gil-Mata S, Ferreira A, Riera-Serra P, Bognanni A, Duarte VH, et al. Efficacy and safety of oral antihistamines for allergic rhinitis: Network meta-analysis. 2025 [link with the full results] | ||
Undesirable EffectsHow substantial are the undesirable anticipated effects? | ||
Judgement | Research evidence | Additional considerations |
Adverse events Following the systematic review performed by Vieira et al., the frequency of patients developing at least one adverse event was assessed in patients under oral H1-antihistamines (OAH) and compared with that registered in patients receiving placebo. A total of 36 randomised controlled trials (RCTs) reported data on the number of patients with seasonal allergic rhinitis reporting at least one adverse event. The meta-analytical risk ratio was of 1.06 (95% confidence interval=0.99; 1.13) [OAH was associated with 10 more cases per 1000 patients than placebo; 95%CI = 2 fewer cases to 23 more cases per 1000 patients. Trivial difference]. A total of 14 RCTs reported data on the number of patients with perennial allergic rhinitis reporting at least one adverse event. The meta-analytical risk ratio was of 0.98 (95% confidence interval=0.91; 1.05) [OAH was associated with 5 fewer cases per 1000 patients than placebo; 95%CI = 24 fewer cases to 13 more cases per 1000 patients. Trivial difference]. Most adverse events which were considered to be related to the treatment were mild and self-limited and comprised headache, nausea, and upper respiratory tract infection. Subgroup considerations: Children and adolescents Two RCTs reported data on the number of children with seasonal allergic rhinitis reporting at least one adverse event. The meta-analytical risk ratio was of 1.07 (95% confidence interval=0.74; 1.53). Five RCTs reported data on the number of children with perennial allergic rhinitis reporting at least one adverse event. The meta-analytical risk ratio was of 1.06 (95% confidence interval=0.86; 1.30). Serious adverse events Following the systematic review performed by Vieira et al., the frequency of patients developing at least one serious adverse event was assessed both in patients under OAH and in patients receiving placebo. For seasonal allergic rhinitis, a total of 30 RCTs compared the frequency of serious adverse events in patients using OAH versus placebo. Most studies did not report any serious adverse event. A total of 8 serious adverse events were reported in 6485 patients using OAH compared to 16 serious adverse events reported in 5545 patients using placebo. None of the serious adverse events reported in patients using OAH were considered to be related to the use of the treatment. For perennial allergic rhinitis, a total of 11 RCTs compared the frequency of serious adverse events in patients using OAH versus placebo. Most studies did not report any serious adverse event. A total of 4 serious adverse events were reported in 2652 patients using OAH compared to 6 serious adverse events reported in 2050 patients using placebo. None of the serious adverse events reported in patients using OAH were considered to be related to the use of the treatment. Subgroup considerations: Children and adolescents No serious adverse events were reported in RCTs assessing children with seasonal or perennial allergic rhinitis treated with OAH. Reference: 1. Vieira RJ, Gil-Mata S, Ferreira A, Riera-Serra P, Bognanni A, Duarte VH, et al. Efficacy and safety of oral antihistamines for allergic rhinitis: Network meta-analysis. 2025 [link with the full results] | ||
Certainty of evidenceWhat is the overall certainty of the evidence of effects? | ||
Judgement | Research evidence | Additional considerations |
The certainty of evidence was moderate for 4 out of 7 analyses, and high for 3 out of 7 analyses.
Reference: 1. Vieira RJ, Gil-Mata S, Ferreira A, Riera-Serra P, Bognanni A, Duarte VH, et al. Efficacy and safety of oral antihistamines for allergic rhinitis: Network meta-analysis. 2025 [link for the certainty of evidence assessments] | ||
ValuesIs there important uncertainty about or variability in how much people value the main outcomes? | ||
Judgement | Research evidence | Additional considerations |
Utility values Symptoms Regarding specific symptoms, in two studies, utilities (measured by VAS) were lower for severe nasal congestion and severe rhinorrhea compared to severe sneezing, severe throat itching, and severe itchy eyes (certainty of evidence: low). When utilities were elicited with the standard gamble technique, severe itchy eyes were rated by US patients as the least preferred AR symptom (certainty of evidence: low).  Studies of rating or ranking of outcomes Adults
 Children/caregivers sample Seven studies assessing children or their caregivers were included in the relative importance analysis. Most of these studies only assessed symptom-related attributes. Similarly to the adult population, a nasal symptom was frequently ranked as the most or second most important attribute (certainty of evidence: low). In particular, nasal congestion was identified as the most important attribute in five studies (certainty of evidence: low).  | ||
Balance of effectsDoes the balance between desirable and undesirable effects favor the intervention or the comparison? | ||
Judgement | Research evidence | Additional considerations |
Taking into account both benefits and harms of oral antihistamines (OAH) versus no treatment, we can consider the following:
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Resources requiredHow large are the resource requirements (costs)?” | ||
Judgement | Research evidence | Additional considerations |
We have included one Swedish study that provides data on the resource use of oral antihistamines. [Cardell 2016]. In this study, mean cost per person of oral antihistamine (OAH) use was €35,4 (n=612, 71,6%) We conducted a survey, having received responses from specialists from 51 countries (mostly in Europe, America and Asia). The costs of being treated for one year with oral antihistamines (OAH) ranged from 4.7 US Dollars Power Purchase Parity (PPP) [Hong Kong] to 743.3 USD PPP [Argentina] (assuming full adherence to treatment and the choice of the least expensive OAH). This corresponds to weekly costs ranging from 0.1 USD PPP to 14.3 USD PPP. The yearly costs per country are displayed in the following map:  Evidence from direct patient data: A preliminary analysis of MASK-air data using the WPAI:AS questionnaire has identified that the overall median work impairment (including both absenteeism and presenteeism) stood at 3.1% (90% CrI: 0.0-28.6%) for well-controlled weeks, ascending to 25.6% (90% CrI: 0.0-65.9%) and 65.4% (90% CrI: 36.6-93.7%) for partially- and poorly-controlled weeks, respectively. In Germany, this translates into median weekly monetary losses of 24.0 USD PPPs for well-controlled weeks, 196.7 USD PPPs for partially-controlled weeks, and 555.4 USD PPPs for poorly controlled weeks (difference of 531.4 USD per week from poor to good control). For other Western European countries, the difference ranges from 262 to 490 USD. References: 1. Cardell LO, Olsson P, Andersson M, Welin KO, Svensson J, Tennvall GR, Hellgren J. TOTALL: high cost of allergic rhinitis-a national Swedish population-based questionnaire study. NPJ Prim Care Respir Med. 2016 Feb 4;26:15082. doi: 10.1038/npjpcrm.2015.82. PMID: 26845513; PMCID: PMC4741287 | Judgement based on gains in productivity (indirect costs) resulting from a better AR control. The societal perspective was adopted to issue this judgement. | |
Certainty of evidence of required resourcesWhat is the certainty of the evidence of resource requirements (costs)? | ||
Judgement | Research evidence | Additional considerations |
Given that oral antihistamines has been around for a long time, there is a reasonably degree of certainty about the general costs. However, it should be noted that available evidence comes from a survey of experts and direct patient data. | ||
Cost effectivenessDoes the cost-effectiveness of the intervention favor the intervention or the comparison? | ||
Judgement | Research evidence | Additional considerations |
We did not identify any cost-effectiveness studies that satisfactorily addressed comparison of oral H1-antihistamines vs. no treatment | ||
EquityWhat would be the impact on health equity? | ||
Judgement | Research evidence | Additional considerations |
We did not identify any equity studies that satisfactorily addressed comparison of oral H1-antihistamines vs. no treatment We conducted a survey, having received responses from specialists from 51 countries (mostly in Europe, America and Asia). At least one oral antihistamine was reported to be available in all 51 countries. Other equity-related aspects  | ||
AcceptabilityIs the intervention acceptable to key interest-holders? | ||
Judgement | Research evidence | Additional considerations |
Satisfaction Evidence from direct patient data: In the MASK-air dataset, there were 7679 days in which OAH were used in monotherapy and for which patients provided information on how satisfied they were with their treatments. The median results of the visual analogue scale were of 84 (higher values indicating higher satisfaction) [IQR=30]. Compliance 4 publications presenting data on acceptability were identified. [Kardas 2013, Koberlain 2013, Belhassen 2022, Szilasi 2012]. All studies were performed in North America or Europe. In the study assessing e-prescriptions for orally administered antihistamines, among the 2280 prescriptions, 1803 (79.1%) were redeemed – the rate of initial non-adherence amounted to 21%. The highest non-adherence (31.3%) was observed in the age group 19 – 39 years, while the highest adherence (84.6% )rate was observed in 75 and older patients. [Kardas 2013] In the post-marketing surveillance study with a total of 42,111 patients taking OAH, the physician graded compliance on a 4-point scale. Compliance was rated by questioning the patient whether the medication had been taken as instructed. During mean treatment duration of 41.6 days, 74.5% and 23.6% of the participants of the model group were “excellent” and “good” in terms of compliance with the intake of the H1-antihistamine. Only 1.6% and 0.3% had a “moderate” and “poor” compliance. [Koberlein 2013] Data from a study involving 3654 French patients with both allergic rhinitis and asthma also suggest a pattern of selective patient acquisition and limited compliance with GP prescriptions. The mean time interval between successive prescriptions was 97 days for antihistamines. On average, individual prescriptions resulted in 1.6 dispensations of antihistamines – patients regularly visited their GPs but irregularly obtained the prescribed therapy. [Belhassen 2022] Adherence One publication presenting data on Hungarian patients’ treatment adherence was identified. [Szilasi 2012]. The optimal adherence regarding antihistamine tablets was reported to be as low as 64.32% for mild and 60.19% for moderate-severe AR patients. Evaluating the possible causes of non-adherence the following were identified: 39.68% of mild AR and 31.49% of moderate-severe AR patients were without symptoms, thus they did not take the tablets. The second most frequent reason of nonadherence with oral treatment was forgetting to take it: this was recorded in 40.48% and 35.91% of mild and moderate/severe AR patients, respectively. Evidence from direct patient data: In complete weeks of MASK-air reporting during the pollen season, there were 38.5% of them in which OAH were used for 6 or 7 days. This compares with 19.6% for intranasal antihistamines, 36.0% for intranasal corticosteroids, and 31.7% for fixed combinations of INAH+intranasal corticosteroids. Switching rate Evidence from direct patient data: In the MASK-air dataset, in 50.1% of the days in which OAH have been used, they have been used in comedication. This compares with 84.8% for INAH, 51.0% for the fixed combination of INAH+intranasal corticosteroids, 56.2% for intranasal corticosteroids, and 83.0% for antagonists of leukotriene receptors. Compared to other rhinitis medication classes, INAH was associated with higher odds of being used in co-medication (OR=2.41; 95%CI=2.07-2.81) in a study using multivariable mixed-effects logistic regression models [Sousa-Pinto]. In 4.1% of days with oral antihistamine use, more than one OAH was used (that is, patients tried at least two OAH on the same day). This compares to 54.8% of days with INAH use, 6.2% of days with intransal corticosteroids use, 4.1% of days with oral antihistamine use, 0.3% of days with fixed combination of INAH+intranasal corticosteroids use, and 0.4% of days with antagonists of leukotriene receptors use. Onset of action In a rapid review of the literature, the median (min-max) onset of action of OAH was found to be 60 min (1 hrs) [15-150 min (0.25-2.5 hrs)] for improvement in nasal symptoms; and 120 min (2 hrs) [75-120 min (1.25-2 hrs)] for improvement in ocular symptoms. References: 1. Kardas G, Panek M, Kuna P, Cieszyński J, Kardas P. Primary Non-Adherence to Antihistamines-Conclusions From E-Prescription Pilot Data in Poland. Front Pharmacol. 2020 May 21;11:783. doi: 10.3389/fphar.2020.00783. PMID: 32528297; PMCID: PMC7253696. 2. Köberlein J, Kothe AC, Sieber J, Mösges R. Determining factors of patient compliance to treatment in allergic rhinitis. Asian Pac J Allergy Immunol. 2013 Jun;31(2):148-56. doi: 10.12932/AP0264.31.2.2013. PMID: 23859415. 3. Belhassen M, Bérard M, Devouassoux G, Dalon F, Bousquet J, Van Ganse E. Treatment of Allergic Rhinitis and Asthma in Primary Care: Dispensations Do Not Align with Prescriptions. J Asthma Allergy. 2022 Nov 25;15:1721-1729. doi: 10.2147/JAA.S376786. PMID: 36457994; PMCID: PMC9707385. 4. Szilasi, M., Gálffy, G., Fónay, K. et al. A survey of the burden of allergic rhinitis in Hungary from a specialist’s perspective. Multidiscip Respir Med 7, 49 (2012). https://doi.org/10.1186/2049-6958-7-49 | ||
FeasibilityIs the intervention feasible to implement? | ||
Judgement | Research evidence | Additional considerations |
Barriers – effectiveness and safety related We have included two studies that provides data on the feasibility of oral antihistamines. [Hellings 2012, Abdullah 2020] – The first survey: study performed in Europe on the patient’s perceived knowledge level, expectations, preferences and fear of side effects – 33% of patients (56/170) feared side effects of oral antihistamines. [Hellings 2012] – The second study was a survey carried out in Southeast Asian Nations (ASEAN) [Abdullah 2020]. When it comes to primary care factors taken into account before recommending antihistamines, GPs are mostly concerned with effectiveness of the medication (94.6%) and pharmacists exhibit greater concerns, particularly about aspects related to usage during pregnancy and breastfeeding (91.6%) and potential side effects like drowsiness (90%), in addition to the drug’s efficacy (96.7%). References: 1. Hellings PW, Dobbels F, Denhaerynck K, Piessens M, Ceuppens JL, De Geest S. Explorative study on patient’s perceived knowledge level, expectations, preferences and fear of side effects for treatment for allergic rhinitis. Clin Transl Allergy. 2012 May 29;2(1):9. doi: 10.1186/2045-7022-2-9. PMID: 22643067; PMCID: PMC3447732. 2. Abdullah B, Snidvongs K, Recto M, Poerbonegoro NL, Wang Y. Primary care management of allergic rhinitis: a cross-sectional study in four ASEAN countries. Multidiscip Respir Med. 2020 Dec 11;15(1):726. doi: 10.4081/mrm.2020.726. PMID: 33376593; PMCID: PMC7750812. | ||
Planetary healthWhat would be the impact on planetary health? | ||
Judgement | Research evidence | Additional considerations |
To assess planetary health, it is usual to perform lifecycle assessment studies, that is, studies assessing the environmental impact of interventions from cradle-to-grave. In a rapid review of the literature, we were unable to find LCA studies assessing oral antihistamines. The following table presents a qualitative summary of topics which may be considered for the assessment of the planetary impact of oral antihistamines across the medication lifecycle.  | ||
Summary of judgements
Judgement | |||||||
|---|---|---|---|---|---|---|---|
Problem | No | Probably no | Probably yes | Yes | Varies | Don’t know | |
Desirable Effects | Trivial | Small | Moderate | Large | Varies | Don’t know | |
Undesirable Effects | Trivial | Small | Moderate | Large | Varies | Don’t know | |
Certainty of evidence | Very low | Low | Moderate | High | No included studies | ||
Values | Important uncertainty or variability | Possibly important uncertainty or variability | Probably no important uncertainty or variability | No important uncertainty or variability | |||
Balance of effects | Favors the comparison | Probably favors the comparison | Does not favor either the intervention or the comparison | Probably favors the intervention | Favors the intervention | Varies | Don’t know |
Resources required | Large costs | Moderate costs | Negligible costs and savings | Moderate savings | Large savings | Varies | Don’t know |
Certainty of evidence of required resources | Very low | Low | Moderate | High | No included studies | ||
Cost effectiveness | Favors the comparison | Probably favors the comparison | Does not favor either the intervention or the comparison | Probably favors the intervention | Favors the intervention | Varies | No included studies |
Equity | Reduced | Probably reduced | Probably no impact | Probably increased | Increased | Varies | Don’t know |
Acceptability | No | Probably no | Probably yes | Yes | Varies | Don’t know | |
Feasibility | No | Probably no | Probably yes | Yes | Varies | Don’t know | |
Planetary health | Reduced | Probably reduced | Probably no impact | Probably increased | Increased | Varies | Don’t know |
Type of recommendation
Conclusions
Recommendation |
For adults with allergic rhinitis, the ARIA guideline panel recommends using oral H1-antihistamines over no treatment (strong recommendation based on moderate certainty of evidence). |
Justification |
Subgroup considerations |
For preschool and school children, the ARIA guideline panel recommends using oral H1-antihistamines over no treatment. |
Implementation considerations |
Current evidence suggests that OAH are not as effective than intranasal medications. However, some patients may still prefer OAH (e.g., refusal of using intranasal medications or corticosteroid-phobia). The evaluation of OAH versus intranasal medications will be the subject of a future guideline paper. |
Monitoring and evaluation |
Research priorities |
Research priorities by domain of the certainty of evidence assessment:
Other research priorities
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