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Can Allergy Medications Harm Your Brain?

Can Allergy Medications Harm Your Brain?

It's allergy season and many of us will be reaching into the medicine cabinet for relief. But it is important to choose wisely, as some allergy medications can harm brain health and increase dementia risk.

Diphenhydramine (e.g., Benadryl®) is a first-generation antihistamine medication [1]. In addition to treating allergy and cold symptoms such as sneezing and watery eyes, it also blocks the actions of acetylcholine. This is a neurotransmitter that is important for brain functions including learning and memory. Diphenhydramine is classified as an anticholinergic drug, and a study of this class of drug found that increased use is associated with an up to 54% increased risk of dementia [2].

In the short-term, side effects of diphenhydramine can include dizziness, drowsiness, confusion, blurred vision, sedation, difficulty urinating, constipation, and low blood pressure [3]. Multiple high-quality human trials have shown that diphenhydramine impairs cognitive functions such as alertness [4], attention [5], memory [5][6][7], executive function [8], reaction time [7], and vigilance [5]. These studies also reported that diphenhydramine increased fatigue and sleepiness while decreasing motivation [5]. An observational study of older hospitalized patients reported that diphenhydramine treatment significantly increased risk for delirium symptoms, including inattention, disorganized speech, and altered consciousness [9]. Older adults with kidney or liver impairment are especially prone to these adverse effects [1]. In fact, diphenhydramine is listed as inappropriate on the Beer's Criteria for Potentially Inappropriate Medication Use in Older Adults [10].


The good news is that newer antihistamines equal the effectiveness of diphenhydramine with few or no cognitive side effects. These medications were developed to minimize adverse events common to diphenhydramine and other older antihistamines [11][12].

  • Desloratadine (e.g., Clarinex®) was tested against diphenhydramine in a study of 204 people. It had no significant effect on sleepiness, working memory, psychomotor speed, reasoning/computation, and divided attention [13]. Diphenhydramine, by contrast, caused impairment on all these measures.
  • Loratadine (e.g., Claritin®) was compared to diphenhydramine in a study of 98 healthy people. The study found that loratadine fared the same as a placebo with regards to side effects while patients taking diphenhydramine reported fatigue, sleepiness, and low motivation, and demonstrated poorer cognitive performance [5].
  • Fexofenadine (e.g., Allegra®) also fared better than diphenhydramine in several studies. In one trial of 42 people, a single dose of diphenhydramine significantly slowed response time, increased omission errors, and increased drowsiness compared with placebo [14]. Fexofenadine did not cause any significant changes. Another trial in 42 aviation personnel found that a single fexofenadine treatment resulted in faster reaction time, fewer omission and commission errors, and better delayed recall accuracy compared to diphenhydramine treatment [15].
  • Cetirizine (e.g., Zyrtec®) was compared to new and old antihistamines. Clinical evidence confirmed that it is more likely to cause sedation than other newer medications options [11]. It does, however, have the fastest onset of action among the newer antihistamines.

If you're older or have concerns about brain health, consider an allergy medication other than diphenhydramine. In addition to the medications above, topical nasal sprays and allergy shots are available by prescription and can also help alleviate symptoms. As always, it's a good idea to discuss your options with a medical professional.


  1. 1. Schroeck JL, Ford J, Conway EL et al. (2016) Review of Safety and Efficacy of Sleep Medicines in Older Adults. Clin There 38, 2340-2372.
  2. Gray SL, Anderson ML, Dublin S et al. (2015) Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med 175, 401-407.
  3. Diphenhydramine. Drugs.com.
  4. Kay GG, Schwartz HI, Wingertzahn MA et al. (2016) Next-day residual effects of gabapentin, diphenhydramine, and triazolam on simulated driving performance in healthy volunteers: a phase 3, randomized, double-blind, placebo-controlled, crossover trial. Hum Psychopharmacol 31, 217-226.
  5. Kay GG, Berman B, Mockoviak SH et al. (1997) Initial and steady-state effects of diphenhydramine and loratadine on sedation, cognition, mood, and psychomotor performance. Arch Intern Med 157, 2350-2356.
  6. Papassotiropoulos A, Gerhards C, Heck A et al. (2013) Human genome-guided identification of memory-modulating drugs. Proc Natl Acad Sci U S A 110, E4369-4374.
  7. Katz IR, Sands LP, Bilker W et al. (1998) Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride. J Am Geriatr Soc 46, 8-13.
  8. Sands L, Katz IR, DiFilippo S et al. (1997) Identification of drug-related cognitive impairment in older individuals. Challenge studies with diphenhydramine. Am J Geriatr Psychiatry 5, 156-166.
  9. Agostini JV, Leo-Summers LS, Inouye SK (2001) Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients. Arch Intern Med 161, 2091-2097.
  10. (2015) Potentially Inappropriate Medication Use in Older Adults 2015. HealthAging.org.
  11. Spangler DL, Brunton S (2006) Efficacy and central nervous system impairment of newer-generation prescription antihistamines in seasonal allergic rhinitis. South Med J 99, 593-599.
  12. Bender BG, Berning S, Dudden R et al. (2003) Sedation and performance impairment of diphenhydramine and second-generation antihistamines: a meta-analysis. J Allergy Clin Immunol 111, 770-776.
  13. Wilken JA, Kane RL, Ellis AK et al. (2003) A comparison of the effect of diphenhydramine and desloratadine on vigilance and cognitive function during treatment of ragweed-induced allergic rhinitis. Ann Allergy Asthma Immunol 91, 375-385.
  14. Mansfield L, Mendoza C, Flores J et al. (2003) Effects of fexofenadine, diphenhydramine, and placebo on performance of the test of variables of attention (TOVA). Ann Allergy Asthma Immunol 90, 554-559.
  15. Bower EA, Moore JL, Moss M et al. (2003) The effects of single-dose fexofenadine, diphenhydramine, and placebo on cognitive performance in flight personnel. Aviat Space Environ Med 74, 145-152.

Yuko Hara, PhD, is Director of Aging and Alzheimer's Prevention at the Alzheimer's Drug Discovery Foundation. Dr. Hara was previously an Assistant Professor in Neuroscience at the Icahn School of Medicine at Mount Sinai, where she remains an adjunct faculty member. Her research focused on brain aging, specifically how estrogens and reproductive aging influence the aging brain's synapses and mitochondria. She earned a doctorate in neurology and neuroscience at Weill Graduate School of Medical Sciences of Cornell University and a bachelor's degree in biology from Cornell University, with additional study at Keio University in Japan. Dr. Hara has authored numerous peer-reviewed publications, including articles in PNAS and Journal of Neuroscience.

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