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#317 Antihistamines for allergic rhinosinusitis: ‘Achoo’sing the right treatment

Do oral antihistamines improve symptoms in adults with allergic rhinosinusitis?

Oral antihistamines reduce rhinosinusitis symptoms by ~10-30% versus placebo over 2-12 weeks. Individual antihistamines appear to have comparable efficacy. More patients attain moderate or better improvement with intranasal corticosteroids (~50%) versus antihistamines (~30%). There appears to be no meaningful differences between antihistamines and leukotriene receptor antagonists or in adding antihistamines to intranasal corticosteroids.

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  • Results statistically significant unless otherwise noted.
  • Antihistamines versus placebo:
    • Systematic review [7 randomized controlled trials (RCTs), 639 patients] of antihistamines versus placebo over 2-12 weeks.1
      • Patient-rated nasal obstruction score (scale 0-3, higher worse), baseline=1.65: Placebo improved symptoms 16% and antihistamines 48%.
    • Systematic review (5 RCTs, 3329 patients) of bilastine (newer antihistamine) versus placebo over 1-12 weeks.2
      • Total symptom score effect size=0.28, similar to improving symptoms 10-16% over placebo.3
    • Other systematic reviews found simiar.4-6
  • Antihistamines versus antihistamines:
    • Systematic reviews showed no statistical or clinical differences in Total or Nasal Symptom Scores between antihistamines.2,7
  • Antihistamines and other agents:
    • Two systematic reviews (5-16 RCTs, 990-2267 patients) compare intranasal corticosteroids to antihistamines over 2-8 weeks.8,9 Total nasal symptom scores improved more with intranasal corticosteroids (51%) versus antihistamines (31%).
      • Proportion attaining moderate control or better10 was higher with intranasal steroids (78%) versus antihistamines (58%), number needed to treat=5.
    • Systematic review (13 RCTs, 5066 patients) of antihistamines plus intranasal corticosteroids versus intranasal corticosteroids alone over 2-6 weeks.11
      • Antihistamine did not add clinically meaningful benefit.
      • Other systematic reviews found similar.12-13
    • Two systematic reviews (9-14 mixed-design studies, 4458-5781 patients) of antihistamines versus leukotriene receptor antagonist over 1-12 weeks: No clinically meaningful differences.14,15
  • Limitations: Too many to list but include per protocol analysis, incorrect meta-analysis techniques, negative studies not published, and scales defined inconsistently.1,7,11,12,15
  • Most antihistamines and many intranasal corticosteroids are available over-the-counter.
  • Adverse event data is infrequently reported, inconsistent, and pooled statistics are generally not clinically interpretable.16 Versus Placebo:
    • Diphenhydramine mild/moderately more sedating (effect size=0.36).
    • Second-generation antihistamines slightly more sedating (effect size=0.14).16
    • Some antihistamines may have less sedation: Fexofenadine versus other second-generation (statistic uninterpretable)17 or bilastine (3%) versus cetirizine (7%).2

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  • Antony Train MBChB MSc CCFP
  • Betsy Thomas BSc. Pharm
  • G. Michael Allan MD CCFP

1. Hore I, Georgalas C, Scadding G. Clin Exp Allergy. 2005 Feb; 35(2):207-12. doi: 10.1111/j.1365-2222.2005.02159.x. Erratum in: Clin Exp Allergy. 2005 Apr; 35(4):547.

2. Singh Randhawa A, Mohd Noor N, Md Daud MK, et al. Front Pharmacol. 2022 Jan 10; 12:731201.

3. Bachert C, Kuna P, Sanquer F, et al. Allergy. 2009 Jan; 64(1):158-65.

4. Canonica GW, Tarantini F, Compalati E, et al. Allergy. 2007 Apr; 62(4):359-66.

5. Compalati E, Baena-Cagnani R, Penagos M, et al. Arch Allergy Immunol. 2011; 156(1):1-15.

6. Mösges R, König V, Köberlein J. Allergol Int. 2011 Dec; 60(4):541-6.

7. Xiao J, Wu WX, Ye YY, et al. Am J Ther. 2016 Nov/Dec; 23(6):e1568-e1578.

8. Juel-Berg N, Darling P, Bolvig J, et al. Am J Rhinol Allergy. 2017 Jan 9; 31(1):19-28.

9. Weiner JM, Abramson MJ, Puy RM. BMJ. 1998 Dec 12; 317(7173):1624-9.

10. Schoenwetter W, Lim J. Clin Ther. 1995 May-Jun; 17(3):479-92

11. Du K, Qing H, Zheng M, et al. Ann Allergy Asthma Immunol. 2020 Nov; 125(5):589-596.e3

12. Feng S, Fan Y, Liang Z, et al. Eur Arch Otorhinolaryngol. 2016 Nov; 273(11):3477-3486.

13. Seresirikachorn K, Chitsuthipakorn W, Kanjanawasee D, et al. Int Forum Allergy Rhinol. 2018 Oct; 8(10):1083-1092.

14. Xu Y, Zhang J, Wang J. PLoS One. 2014 Nov 10; 9(11):e112815.

15. Feng Y, Meng YP, Dong YY, et al. Allergy Asthma Clin Immunol. 2021 Jun 29; 17(1):62.

16. Bender BG, Berning S, Dudden R, et al. J Allergy Clin Immunol. 2003 Apr; 111(4):770-6.

17. Huang CZ, Jiang ZH, Wang J, et al. BMC Pharmacol Toxicol. 2019 Nov 29; 20(1):72.

Authors do not have any conflicts of interest to declare.