Question | |
Should nasal decongestants vs. no treatment be used for the treatment of allergic rhinitis? | |
Population: | Patients with allergic rhinitis |
Intervention: | nasal decongestants |
Comparison: | no treatment |
Main outcomes: | Nasal symptoms Ocular symptoms Quality of life Adverse events (any) Serious adverse events |
Setting: | |
Perspective: | |
Background: | Intranasal decongestants (oxymetazoline, xylometazoline and tramazoline) are frequently used by patients with allergic rhinitis, particularly considering that they are commonly sold over-the-counter and display a fast onset of action in nasal congestion. |
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 |
Conducting a rapid evidence review, we identified one systematic review evaluating nasal decongestants (oxymetazoline) in patients with chronic rhinitis[1] . No systematic reviews were identified for the remaining decongestants. A rapid review of the references of the identified systematic review alongside a search in AI-based platforms and in MEDLINE led to identification of two randomised controlled trials comparing a decongestant (oxymetazoline) to placebo, one performed in patients with perennial allergic rhinitis and another performed in patients with seasonal allergic rhinitis. Nasal symptoms The trial performed in patients with seasonal allergic rhinitis [2] identified that oxymetazoline (compared to placebo) was associated with an improvement of the total nasal symptom score [TNSS] (mean difference of the change from baseline=-0.54; 95%CI=-1.13;0.05; p-value=0.071). This difference was compatible with both small benefits and a trivial effect. When considering nasal congestion isolated, oxymetazoline was not associated with a significant improvement compared to placebo. Of note, the reported nasal symptoms in that trial were the instantaneous and not the reflective ones. The trial performed in patients with perennial allergic rhinitis [3] did not report significant differences when comparing the effect of oxymetazoline versus placebo on the TNSS (mean difference of the change from baseline=0.43; no information on spread measures). Ocular symptoms No studies were identified allowing for the comparison between decongestants versus placebo on their effect on the total ocular symptom score (TOSS). Quality of life The trial performed in patients with seasonal allergic rhinitis [2] identified that oxymetazoline (compared to placebo) was not associated with a significant improvement of the rhinoconjunctivitis quality of life questionnaire [RQLQ] (mean difference of the change from baseline=-0.22; no information on spread measures). The trial performed in patients with perennial allergic rhinitis [3] did not report significant differences when comparing the effect of oxymetazoline versus placebo on the RQLQ (mean difference of the change from baseline=-0.21; 95%CI=-1.10;1.52; p-value=0.753). The point estimate is compatible with a trivial effect, but – given the observed imprecision – the confidence interval is compatible with effects that range from moderate benefits to large harms. References 1. Neighbors CL, Salvador CF, Zhu B, Camacho M, Tsai P. Intranasal corticosteroid and oxymetazoline for chronic rhinitis: a systematic review. J Laryngol Otol. 2022;136(1):8-16. 2. Meltzer EO, Bernstein DI, Prenner BM, et al. Mometasone furoate nasal spray plus oxymetazoline nasal spray: short-term efficacy and safety in seasonal allergic rhinitis. Am J Rhinol Allergy. 2013;27(2):102-108. 3. Baroody FM, Brown D, Gavanescu L, DeTineo M, Naclerio RM. Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis. J Allergy Clin Immunol. 2011;127(4):927-934. | Overall, the literature points to a limited role of intransal decongestants, particularly in the short-term relief of nasal congestion. | |
Undesirable EffectsHow substantial are the undesirable anticipated effects? | ||
Judgement | Research evidence | Additional considerations |
NOTE: None of the primary studies assessed phenylephrine or pseudoephedrine. The decongestant assessed in included primary studies was oxymetazoline. The long-term use of nasal decongestants has been linked to rhinitis medicamentosa. Conducting a rapid evidence review, we identified one systematic review evaluating nasal decongestants (oxymetazoline) in patients with chronic rhinitis[1] . No systematic reviews were identified for the remaining decongestants. A rapid review of the references of the identified systematic review alongside a search in AI-based platforms and in MEDLINE led to identification of two randomised controlled trials comparing a decongestant (oxymetazoline) to placebo, one performed in patients with perennial allergic rhinitis and another performed in patients with seasonal allergic rhinitis. Adverse events The trial performed in patients with seasonal allergic rhinitis [2] identified that oxymetazoline (compared to placebo) was associated with a higher risk of developing at least one adverse event compared to placebo (meta-analytical risk ratio of 1.13; 95%CI=0.47-2.83) [oxymetazoline were associated with 7 more cases per 1000 patients than placebo; 95%CI= 31 fewer cases to 105 more cases per 1000 patients. Trivial difference]. The trial performed in patients with perennial allergic rhinitis [3] identified that oxymetazoline (compared to placebo) was associated with a higher risk of developing at least one adverse event compared to placebo (meta-analytical risk ratio of 1.23; 95%CI=0.50-3.00) [oxymetazoline were associated with 80 more cases per 1000 patients than placebo; 95%CI=179 fewer cases to 715 more cases per 1000 patients. Trivial effect to moderate harms]. Most adverse events which were considered to be related to the treatment were mild and self-limited. Assessing pharmacovigilance data, the most frequent reported adverse events associated with the use of oxymetazoline, xylometazoline and tramazoline were drug dependence, anosmia/ageusia, nasal discomfort, epistaxis, headache and nasal congestion. Subgroup considerations: Children and adolescents In a retrospective cohort study [4] , which included all children below 2 years of age who were admitted to a general teaching hospital in the Netherlands between 1 April 2017 and 1 April 2021 and were treated with saline nasal spray/drops with or without xylometazoline, the risk for adverse events was compared between the two treatments. In that study, xylometazoline presented an overall safe profile, with a lower incidence of adverse events compared to saline alone. Serious adverse events Serious adverse events were not reported in the two included trials. Assessing pharmacovigilance data, the most frequent reported serious adverse event with the use of oxymetazoline, xylometazoline and tramazoline was drug dependence. There have been studies reporting on possible [rare] teratogenic effects (e.g., gastroschisis, pyloric stenosis, and renal abnormalities) from the use of nasal decongestants (such as oxymetazoline) in the first trimester of pregnancy [5]. There have also been reports that, in the elderly, nasal decongestants may be associated with a worsening of hypertension, prostatism and arrhythmia [6]. References 1. Neighbors CL, Salvador CF, Zhu B, Camacho M, Tsai P. Intranasal corticosteroid and oxymetazoline for chronic rhinitis: a systematic review. J Laryngol Otol. 2022;136(1):8-16. 2. Meltzer EO, Bernstein DI, Prenner BM, et al. Mometasone furoate nasal spray plus oxymetazoline nasal spray: short-term efficacy and safety in seasonal allergic rhinitis. Am J Rhinol Allergy. 2013;27(2):102-108. 3. Baroody FM, Brown D, Gavanescu L, DeTineo M, Naclerio RM. Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis. J Allergy Clin Immunol. 2011;127(4):927-934. 4. van Stralen KJ, van Tol JE, de Wildt SN, et al. Use of xylometazoline in hospitalised infants: is it safe? A retrospective cohort study. Arch Dis Child. 2023;108(1):62-66. 5. Yau WP, Mitchell AA, Lin KJ, Werler MM, Hernandez-Diaz S. Use of decongestants during pregnancy and the risk of birth defects. Am J Epidemiol 2013;178 (2):198-208. 6. Hansen J, Klimek L, Hörmann K. Pharmacological management of allergic rhinitis in the elderly: safety issues with oral antihistamines. Drugs Aging. 2005;22(4):289-296. | ||
Certainty of evidenceWhat is the overall certainty of the evidence of effects? | ||
Judgement | Research evidence | Additional considerations |
The certainty of evidence was very low for 2 out of 6 analyses, low for 3 out of 6 analyses and moderate for 1 analysis.
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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).  Inc - Certainty of evidence was lowered due to inconsistency; R- Certainty of evidence was lowered due to risk of bias; Ind- Certainty of evidence was lowered due to indirectness; Imp- Certainty of evidence was lowered due to imprecision, ⨁⨁⨁⨁ high certainty of evidence, ⨁⨁⨁◯ moderate certainty of evidence, ⨁⨁◯◯ low certainty of evidence 4 We rated down the certainty of evidence for indirectness because an indirect measurement tool was used to elicit the utility of outcomes with scale of 0 to 1, where 0 indicated the worst symptom(s) and 1 represented no symptom(s).5 Small sample size of the included study. 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 nasal decongestants versus no treatment, we can consider the following:
| This judgment is applicable to long-term use of nasal decongestants (particularly considering its adverse events such as rhinitis medicamentosa), and not to their short-term use to relief nasal congestion. | |
Resources requiredHow large are the resource requirements (costs)?" | ||
Judgement | Research evidence | Additional considerations |
We conducted a survey, having received responses from specialists from 41 countries (mostly in Europe, America and Asia). Oxymetazoline was available in 33 countries, tramazoline was available in 15 countries and xylometazoline in 34. Only 13 countries had all three intranasal decongestants available. The costs of being treated for one year with intranasal decongestants ranged from 2.4 US Dollars Power Purchase Parity (PPP) [Bangladesh] to 498.1 USD PPP [Argentina] (assuming full adherence to treatment and the choice of the least expensive). This corresponds to weekly costs ranging from 0.05 USD PPP to 10.4 USD PPP. The yearly costs per country associated with the use of intranasal decongestants are displayed in the following map:  | ||
Certainty of evidence of required resourcesWhat is the certainty of the evidence of resource requirements (costs)? | ||
Judgement | Research evidence | Additional considerations |
Evidence on the costs of decongestants was obtained from a survey of experts. | ||
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-utility studies that satisfactorily addressed comparison of decongestants vs. no treatment. | ||
EquityWhat would be the impact on health equity? | ||
Judgement | Research evidence | Additional considerations |
Availability We conducted a survey, having received responses from specialists from 41 countries (mostly in Europe, America and Asia). At least one intranasal decongestant was reported to be available in all assessed countries, with an exception for Syria and Croatia. Oxymetazoline was available in 33 out of 41 countries. Tramazoline was available in 15 countries and xylometazoline in 34. Only 13 countries had all three intranasal decongestants available. Other equity-related aspects  1. Lundberg L and Isacson D. The impact of over-the-counter availability of nasal sprays on sales, prescribing, and physician visits. Scandinavian Journal of Primary Health Care. 1999;17(1),41–45. | ||
AcceptabilityIs the intervention acceptable to key interest-holders? | ||
Judgement | Research evidence | Additional considerations |
Co-medication use Evidence from direct patient data: In the MASK-air dataset, in 68.1% of the days in which intranasal decongestants have been used, they have been used in comedication. This compares with 50.1% for oral antihistamines, 51.0% for the fixed combinations of intranasal antihistamines + intranasal corticosteroids, 56.2% for intranasal corticosteroids, 83.0% for antagonists of leukotriene receptors, and 84.8% for intranasal antihistamines. In 1.0% of the days with decongestant use, more than one decongestant was used (that is, patients tried at least two decongestants on the same day). This compares to 54.8% of days with INAH use, 6.2% of days with intranasal corticosteroids use, 4.1% of days with oral antihistamine use, 0.3% of days with fixed combination of intranasal antihistamines + intranasal corticosteroids use, and 0.4% of days with antagonists of leukotriene receptors use. Compliance (patient) Evidence from direct patient data: In complete weeks of MASK-air reporting during the pollen season, there were 5.3% in which intranasal decongestants were used for 6 or 7 days. This compares with 19.6% for intranasal antihistamines, 36.0% for intranasal corticosteroids, 38.5% for oral antihistamines, and 31.7% for fixed combinations of intranasal antihistamines + intranasal corticosteroids. Satisfaction Evidence from direct patient data: In the MASK-air dataset, there were 259 days in which intranasal decongestants 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 63 (higher values indicating higher satisfaction) [IQR=49]. Onset of action A rapid review of the literature on the onset of action of intranasal decongestants was carried out and no relevant results were found when using intranasal decongestants in allergic rhinitis. However, the following results were found in the context of acute rhinitis [1]: “On average, the effect of oxymetazoline set in after 25 seconds, as compared with 90 seconds for physiological saline.” In another study [2], it was concluded that the decongestant action of Xylometazoline 0.1% solution as quantified by Nasal peak Flowmetry begins within 10 minutes of application. References: 1. Reinecke S, Tschaikin M. Untersuchung der Wirksamkeit von Oxymetazolin auf die Rhinitisdauer. Ergebnisse einer plazebokontrollierten Doppelblindstudie bei akuter Rhinitis [Investigation of the effect of oxymetazoline on the duration of rhinitis. results of a placebo-controlled double-blind study in patients with acute rhinitis]. MMW Fortschr Med. 2005;147(3):113-8. 2. Rajamani SK. Effect of Topical Nasal Decongestants on Nasal Peak Flow Rates in Adults Suffering from Acute Sinusitis. Bengal Journal of Otolaryngology and Head Neck Surgery. 2018;26(2):86-90. | ||
FeasibilityIs the intervention feasible to implement? | ||
Judgement | Research evidence | Additional considerations |
We did not identify any studies that adequately addressed the feasibility of intranasal decongestants. | ||
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 intranasal decongestants. | ||
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 |
In patients with allergic rhinitis, the ARIA guideline panel suggests against using intranasal decongestants in the long term (longer than 5 days) over no treatment. (Conditional recommendation based on very low certainty of evidence) |
Justification |
This decision is mostly grounded on (i) lack of important desirable effects, (ii) risk of undesirable effects, (iii) resources required, and (iv) impact on planetary health. |
Subgroup considerations |
For preschool and school children, the ARIA guideline panel suggests against using intranasal decongestants in the long term over no treatment. There should be avoidance of intranasal decongestants in pregnant women, especially in the first trimester, considering the potential teratogenic effects of nasal decongestants. Considering the risk of serious adverse events, the use of intranasal decongestants in the elderly is also discouraged. |
Implementation considerations |
This recommendation concerns oxymetazoline, xylometazoline and tramazoline. The panel suggests that the use of intranasal decongestants should be restricted to short-term relief (not longer than 5 days and preferably shorter) of nasal congestion. The ARIA panel also recommends against the use of ephedrine-based decongestants due to safety and legal concerns. |
Monitoring and evaluation |
Research priorities |
- Need for studies in specific subgroups of participants or presentation of results by subgroup. Such subgroups include: children and adolescents, older patients, patients with multimorbidity (asthma and conjunctivitis), and patients from ethnic minorities. - Need for more well-conducted randomised controlled trials, particularly (i) evaluating participants with perennial allergic rhinitis and those with mild allergic rhinitis, and (ii) having ocular symptoms as an outcome. - Need for studies evaluating the planetary impact and cost-effectiveness of the intervention. |