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Glacy J, Putnam K, Godfrey S, et al. Treatments for Seasonal Allergic Rhinitis [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013 Jul. (Comparative Effectiveness Reviews, No. 120.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.



Seasonal allergic rhinitis (SAR), also known as hay fever, is an inflammatory condition of the upper airways that occurs in response to exposure to airborne allergens (typically tree, grass, and weed pollens and some molds) in sensitized individuals. Although there is geographic variability in the seasonal emergence of allergenic pollens across the United States (U.S.), tree pollens tend to emerge in the spring, grass pollens in the summer, and weed pollens in the fall. Outdoor molds generally are prevalent in the summer and fall. SAR is distinguished from perennial allergic rhinitis (PAR), which is triggered by continuous exposure to house dust mites, animal dander, and other allergens generally found in an individual's indoor environment. Patients may have either SAR or PAR or both (i.e., PAR with seasonal exacerbations). Regardless of the inciting allergen(s), the four defining symptoms of allergic rhinitis are nasal congestion, nasal discharge (rhinorrhea), sneezing, and/or nasal itch. Many patients also experience symptoms of allergic conjunctivitis, such as itchy and watery eyes.1 Treatment effectiveness is assessed by improvement of these symptoms and improved quality of life. Additional signs of rhinitis include the allergic salute (rubbing the hand against the nose in response to itching and rhinorrhea), allergic shiner (bruised appearance of the skin under one or both eyes), and allergic crease (a wrinkle across the bridge of the nose caused by repeated allergic salute).2-5


Traditionally, allergic rhinitis syndromes were categorized as SAR, PAR, and PAR with seasonal exacerbation.3 This is the classification scheme we used for our report. In 2001, the Allergic Rhinitis and its Impact on Asthma (ARIA) international working group proposed a new classification scheme consisting of four categories based on rhinitis severity and duration: 1) mild intermittent, 2) mild persistent, 3) moderate/severe intermittent, and 4) moderate/severe persistent.6 This new scheme suggests a stepwise treatment approach according to the severity and duration of symptoms.2 However, the new scheme is not interchangeable with the traditional one, as different patient populations are defined by each.3, 7 In 2008, the American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) updated a Joint Task Force Practice Parameter on the diagnosis and management of rhinitis. The update retained the terms seasonal and perennial because “[t]hese traditional descriptive terms are clinically useful and allow for accurate categorization of the vast majority of patients.”3 For our report, we searched for trials involving patients with seasonal allergic rhinitis only.

Burden of Disease

SAR afflicts approximately 10 percent of the U.S. population, or 30 million individuals.8, 9 In 2009, 17.7 million U.S. adults (7.8 percent) were diagnosed with hay fever, and 7.2 million U.S. children (9.8 percent) reported having had hay fever in the previous 12 months.10, 11 The 2007 Pediatric Allergies in America survey revealed that 313 (62 percent) of 500 children (younger than 18 years of age) diagnosed with allergic rhinitis had SAR. SAR has been demonstrated to adversely affect quality of life,12-14 sleep,15, 16 cognition,17 emotional life,18 and work or school performance.19-21


Medications used to treat SAR target biochemical pathways that cause characteristic symptoms. SAR results from the binding of an inhaled aeroallergen to immunoglobulin E (IgE) on the surface of mast cells in the nasal mucosa. An early phase allergic response follows: Mast cell degranulation releases preformed inflammatory mediators, such as histamine, which produce immediate nasal itch and sneezing. Histamine stimulation of the histamine-1 (H1) receptors on sensory nerves causes vascular dilation and increased plasma leakage. Mucus secretion from nasal glands is stimulated directly by leukotrienes and indirectly by activated parasympathetic (cholinergic) nerve fibers. Leukotrienes also increase vascular permeability. The result is nasal discharge and congestion, which is maximal after 15 to 30 minutes. Four to 12 hours after allergen exposure, a late-phase allergic response may occur. The late-phase response consists primarily of nasal congestion and is mediated by the influx and activation of inflammatory T-cells, basophils, and eosinophils.2, 22, 23 Ongoing, prolonged allergen exposure and repeated late-phase responses lead to progressive inflammation of the nasal mucosa and increased allergen sensitivity. The amount of allergen capable of eliciting an allergic response lessens over time, an effect termed priming. The priming effect is thought to explain the development of mucosal hyper-responsiveness to nonallergen triggers, such as strong odors, cigarette smoke, and cold temperatures.22, 24 It also provides the rationale for initiating effective rhinitis therapies prophylactically before the commencement of pollen season.25


Treatments for allergic rhinitis comprise allergen avoidance, pharmacotherapy, and immunotherapy. Although allergen avoidance may be the preferred treatment, for SAR, total allergen avoidance may be an unrealistic approach, as it may require limiting time spent outdoors. Thus, pharmacotherapy is preferable to allergen avoidance for symptom relief of SAR. Allergen-specific immunotherapy is the subject of a separate review, also sponsored by the Agency for Healthcare Research and Quality (AHRQ) and posted on the Effective Health Care Web site (www.effectivehealthcare.ahrq.gov/reports/final/cfm). Six classes of drugs and nasal saline are used to treat SAR. Several drugs have more than one route of administration (e.g., intranasal and oral), as described below.

  • Antihistamines used to treat allergic rhinitis target the H1 receptor. Oral antihistamines are classified as selective and nonselective for peripheral H1 receptors. Nonselective antihistamines (e.g., diphenhydramine) bind central H1 receptors, which can cause sedation. They also bind cholinergic, α-adrenergic, and serotonergic receptors, which can potentially cause other adverse effects such as dry mouth, dry eyes, urinary retention, constipation, and tachycardia. Nonselective antihistamines are associated with impaired sleep, learning, and work performance and with motor vehicle, boating, and aviation accidents.26 The selective antihistamines (e.g., loratadine), in contrast, are more specific for peripheral H1 receptors and do not cross the blood-brain barrier to bind central H1 receptors. Adverse effects, such as sedation, are therefore reduced.27 The choice of which antihistamine to use may be influenced by cost, insurance coverage, adverse effect profile, patient preference, and drug interactions.27 All nonselective and some selective antihistamines are metabolized by hepatic cytochrome P450 enzymes. Plasma concentrations of these drugs are increased by cytochrome P450 inhibitors, such as macrolide antibiotics and imidazole antifungals.2 Two nasal antihistamines—azelastine and olopatadine—are currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of SAR. Adverse effects of nasal antihistamines may include a bitter aftertaste.
  • Corticosteroids are potent anti-inflammatory molecules. Intranasal corticosteroids are recommended as first-line treatment for moderate/severe or persistent allergic rhinitis.3, 28 However, whether they are superior to or equally effective as nasal antihistamines for the relief of nasal congestion is uncertain,29, 30 particularly in patients with mild allergic rhinitis. Many preparations with differing pharmacokinetic and pharmacodynamic profiles exist. These can be used continuously (daily) during allergy season or as needed. It is unclear which approach is more effective in which patients or how benefits balance against potential adverse effects of each approach. Intranasal corticosteroids do not appear to cause adverse events associated with systemic absorption (e.g., adrenal suppression, bone fracture among the elderly, and reduced bone growth and height in children). Adverse local effects may include increased intraocular pressure and nasal stinging, burning, bleeding, and dryness. Aqueous formulations and proper technique may help to relieve these effects. Little is known about cumulative corticosteroid effects in patients who take concomitant oral or inhaled formulations for other diseases. For patients with persistent symptoms, it also is unclear whether adding oral or nasal antihistamine to intranasal corticosteroid provides any additional benefit. Oral corticosteroids are occasionally prescribed for short courses (5 to 7 days) as needed in patients with severe symptoms unresponsive to other treatments.3 Because there is no alternative to this specific use of corticosteroids in SAR, oral corticosteroids are not reviewed in this report. Similarly, although FDA-approved for SAR, intramuscular corticosteroid injections are not recommended for the treatment of SAR3, 28 and are not reviewed in this report.
  • Decongestants are α-adrenergic agonists that produce vasoconstriction. In the nasal mucosa, this results in decreased vascular engorgement and edema with subsequent reduction of nasal obstruction. Intranasal decongestants (e.g., oxymetazoline) may be administered before intranasal corticosteroid or nasal antihistamine to increase delivery of these drugs in patients with very severe nasal airway obstruction. Rhinitis medicamentosa, a rebound of congestion with symptom worsening, may occur with several days of use, although the exact interval and the actual proportion of patients who develop this problem are unknown. Other local adverse effects may include nosebleeds, stinging, burning, and dryness. Oral decongestants (e.g., phenylephrine, pseudoephedrine) are used alone and often are found in combination products marketed for the relief of colds and sinus congestion. Because pseudoephedrine is a key ingredient used for illicit methamphetamine production, its sale in the U.S. is restricted, resulting in the substitution of phenylephrine for pseudoephedrine in many over-the-counter cold and cough remedies. Systemic adverse effects of decongestants may include hypertension, irritability, tachycardia, dizziness, insomnia, headaches, anxiety, sweating, and tremors.2, 31 Decongestants are used with caution, if at all, in patients with diabetes mellitus, ischemic heart disease, unstable hypertension, prostatic hypertrophy, hyperthyroidism, and narrow-angle glaucoma. Oral decongestants are contraindicated with coadministered monoamine oxidase inhibitors and in patients with uncontrolled hypertension or severe coronary artery disease.32
  • Ipratropium is an anticholinergic agent that blocks parasympathetic nerve conduction and the production of glandular secretions within the nasal mucosa. Ipratropium nasal spray is approved by the FDA for treating rhinorrhea associated with SAR. Postmarketing experience suggests that there may be some systemic absorption; it is unclear whether this issue has been addressed in the peer-reviewed literature. Cautious use is advised for patients with narrow-angle glaucoma, prostatic hypertrophy, or bladder neck obstruction, particularly if another anticholinergic is coadministered by another route. Local adverse effects may include nosebleeds and nasal and oral dryness. Efficacy and safety beyond three weeks in patients with SAR have not been established.33
  • Intranasal mast cell stabilizers inhibit the antigen-induced release of inflammatory mediators from mast cells. Cromolyn is the only mast cell stabilizer approved by the FDA for the treatment of SAR. It is commonly administered prophylactically, before an allergic reaction is triggered, during a loading period in which it is used four times daily for several weeks. As-needed use also has been described and may be of benefit. Systemic absorption is minimal. Local adverse effects may include nasal irritation, sneezing, and an unpleasant taste.2, 31
  • Cysteinyl leukotrienes are biological inflammatory mediators. Leukotriene receptor antagonists are oral medications that reduce allergy symptoms by inhibiting inflammation.34, 35 Montelukast is the only leukotriene receptor antagonist approved by the FDA for the treatment of SAR. Potential adverse effects include upper respiratory tract infection and headache.31

Nasal Saline

A 2007 Cochrane evidence review indicated that nasal saline is beneficial in treating nasal SAR symptoms.36 Because it is associated with few adverse effects, nasal saline may be particularly well suited for treating SAR symptoms during pregnancy, in children, and in those whose treatment choices are restricted due to comorbidities, such as hypertension and urinary retention.


The optimal treatment of SAR during pregnancy is unknown. Drugs that were effective before pregnancy may be effective during pregnancy, but their use may be restricted because of concerns about maternal and fetal safety. Because pregnancy is often an explicit exclusion criterion for clinical trials, data demonstrating efficacy and maternal and fetal safety are lacking for most drugs, including those used for SAR. Decisions about which treatments are best during pregnancy must weigh the potential treatment-related risks and benefits to both mother and fetus against the potential risks and benefits of enduring the symptoms of the disease. Drugs used to treat SAR are Pregnancy Category B (presumed safe based on animal studies but without adequate human data) or Category C (of uncertain safety, with no demonstrated adverse effects in animals or humans). The risk of congenital malformation is greatest during organogenesis in the first trimester. If medication cannot be avoided during this time, intranasal treatments with minimal systemic effects, such as nasal cromolyn (Pregnancy Category B) and nasal saline, are preferred.3 Of the intranasal corticosteroids, only intranasal budesonide is Pregnancy Category B; the others are Category C. The intranasal anticholinergic, ipratropium, also is Pregnancy Category B. The safety of intranasal decongestants during pregnancy has not been studied. Pregnancy Category B oral medications that may be considered for use after the first trimester include the selective antihistamines loratadine, cetirizine, and levocetirizine; several nonselective antihistamines (chlorpheniramine, clemastine, cyproheptadine, dexchlorpheniramine, and diphenhydramine); and the leukotriene receptor antagonist, montelukast. Oral decongestants are generally avoided during pregnancy, especially during the first trimester.


Most pharmacologic treatments for SAR are approved for use in adults and adolescents older than 12 years of age. For children, toddlers, and infants, treatment choices are limited due to safety concerns. Thus, optimal treatments for these age groups have been difficult to identify. For children who are able and willing to use intranasal medication, nasal saline presents a treatment choice with few potential adverse events. Similarly, nasal cromolyn is approved for use in children older than 2 years of age. Intranasal corticosteroids (e.g., fluticasone, mometasone, and triamcinolone) are approved for use in children as young as 2 years of age. Potential adverse events resulting from systemic absorption, such as impaired bone growth, reduced height, suppression of the adrenal axis, hyperglycemia, and weight gain, have not been definitively demonstrated.

Children with occasional symptoms may be treated with antihistamines on days when symptoms are present or expected. Carbinoxamine is a nonselective antihistamine approved for use in infants. The selective antihistamines loratadine, desloratadine, and cetirizine are approved by the FDA for use in children older than 2 years of age. Nasal antihistamines are approved for children older than 5 (azelastine) or older than 12 (olopatadine) years of age. In children older than 6 years of age, oral decongestants generally have few adverse effects at age-appropriate doses. However, in infants and young children, the use of oral decongestants may be associated with agitated psychosis, ataxia, hallucinations, and death.3 Extended-release formulations are not recommended for children younger than 12 years of age.

Scope of the Review

The scope of this review is the comparative effectiveness and harms of pharmacologic treatments for SAR in three patient populations: adults and adolescents 12 years of age and older; pregnant women; and children younger than 12 years of age. Drug classes of interest are: oral and nasal antihistamines and decongestants; intranasal corticosteroids, mast cell stabilizers (cromolyn), anticholinergics (ipratropium), and saline; and oral leukotriene receptor antagonists (montelukast). Included drugs were FDA-approved for SAR. For pregnant women, included drugs were limited to Pregnancy Category B. For children, drugs that are seldom used in patients younger than 12 years (oral and nasal decongestant and nasal anticholinergic [ipratropium]) were not included. Outcomes of interest were patient-reported improvements in symptoms and quality of life and common adverse effects of treatment. We limited this review to direct comparisons of the six drug classes listed above. However, not all class comparisons are clinically relevant: for example, comparison of intranasal anticholinergic (ipratropium), which treats rhinorrhea, to intranasal sympathomimetic decongestant, which treats nasal congestion. The Technical Expert Panel (TEP) provided input as to the relevant class comparisons. Ideally, for each relevant comparison, all drugs within each class would be compared. However, the evidence base is not complete in this respect, and the proportion of drugs represented for any class studied ranged from five of five oral selective antihistamines to zero (intranasal sympathomimetic decongestants, anticholinergic [ipratropium], and nasal saline).

Although a comparison of short-term (weeks) and long-term (months) effectiveness and harms is desirable, we sought evidence from real-world treatment of symptomatic patients. Such studies are necessarily limited by natural pollen cycles, typically 8 to 10 weeks, and do not provide evidence on longer-term effectiveness and harms of SAR treatments. Studies of simulated exposure to aeroallergens are not reviewed here.

Although there are multiple guidelines for the treatment of allergic rhinitis,3, 28, 37-40 the guidelines are not consistently based on systematic reviews of the literature and often do not address the treatment of SAR in children and pregnant women. Guidelines generally support the use of intranasal corticosteroids as first-line treatment of moderate/severe SAR. However, agreement is lacking about four other issues of importance to patients and clinicians:

  1. First-line treatment for mild SAR.
  2. The comparative effectiveness and safety of SAR treatments used in combination with each other for both mild and moderate/severe SAR.
  3. The comparative effectiveness of as-needed use compared with daily dosing.
  4. The comparative effectiveness and harms of SAR treatments for eye symptoms and asthma symptoms that often co-occur with SAR

This review addresses the four issues above. The scope of this review is comparisons across pharmacologic classes. With input from the TEP, we decided to focus on across-class comparisons, as this is the first question that patients, clinicians, and other decisionmakers face. Although there may be differences among drugs within the same class, previous comparative effectiveness reviews in allergic rhinitis3, 28, 38, 41-47 have found insufficient evidence to support superior effectiveness of any single drug within a drug class. A direct consequence of the decision to conduct across-class comparisons is the inability to compare individual drugs across studies. Additionally, limited conclusions can be drawn about drug classes that are poorly represented by the drugs studied. To our knowledge, methodological approaches for meta-analysis of class comparisons based on studies of single treatment comparisons have not been published.

Key Questions

Key Question 1. What is the comparative effectiveness of pharmacologic treatments, alone or in combination with each other, for adults and adolescents (≥12 years of age) with mild or with moderate/severe SAR?

  1. How does effectiveness vary with long-term (months) or short-term (weeks) use?
  2. How does effectiveness vary with intermittent or continuous use?
  3. For those with symptoms of allergic conjunctivitis, does pharmacologic treatment of SAR provide relief of eye symptoms (itching, tearing)?
  4. For those codiagnosed with asthma, does pharmacologic treatment of SAR provide asthma symptom relief?

Key Question 2. What are the comparative adverse effects of pharmacologic treatments for SAR for adults and adolescents (≥12 years of age)?

  1. How do adverse effects vary with long-term (months) and short-term (weeks) use?
  2. How do adverse effects vary with intermittent or continuous use?

Key Question 3. For the subpopulation of pregnant women, what are the comparative effectiveness and comparative adverse effects of pharmacologic treatments, alone or in combination with each other, for mild and for moderate/severe SAR?

  1. How do effectiveness and adverse effects vary with long-term (months) or short-term (weeks) use?
  2. How do effectiveness and adverse effects vary with intermittent or continuous use?

Key Question 4. For the subpopulation of children (<12 years of age), what are the comparative effectiveness and comparative adverse effects of pharmacologic treatments, alone or in combination with each other, for mild and for moderate/severe SAR?

  1. How do effectiveness and adverse effects vary with long-term (months) or short-term (weeks) use?
  2. How do effectiveness and adverse effects vary with intermittent or continuous use?

The analytic framework for this report is presented in Figure 1. The figure depicts the Key Questions (KQs) in relation to SAR treatments, adverse effects, and outcomes. The six drug classes of SAR treatments and nasal saline may produce intermediate outcomes such as relief of rhinitis symptoms and, if present, eye and asthma symptoms. Treatments also may result in improved quality of life, the final health outcome. Adverse events may occur at any point after treatment is received and may impact quality of life directly.

Figure 1 depicts the analytic framework and key questions in relation to SAR treatments, adverse effects, and outcomes. The figure illustrates how antihistamines, corticosteroids, decongestants, mast cell stabilizers, leukotriene receptor antagonists, ipratropium, and nasal saline used for the treatment of seasonal allergic rhinitis may result in intermediate outcomes such as relief of rhinitis symptoms and, if present, eye and asthma symptoms. Treatments also may result in improved quality of life, the final health outcome. Adverse events may occur at any point after treatment is received and may impact quality of life directly. Examples of adverse events that may occur include local adverse events, such as nosebleeds and glaucoma, as well as systemic adverse events, such as sedation, impaired school or work performance, growth delay, fracture, urinary retention, hyperglycemia, and palpitations.

Figure 1

Analytic framework. KQ = Key Question; SAR = seasonal allergic rhinitis.

Cover of Treatments for Seasonal Allergic Rhinitis
Treatments for Seasonal Allergic Rhinitis [Internet].
Comparative Effectiveness Reviews, No. 120.
Glacy J, Putnam K, Godfrey S, et al.


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