Allergy Season — It can affect your thinking !!!
George Luciuk, MD, FRCPC, Vancouver, B.C.
For people with seasonal allergies, the period from early spring to late fall can be difficult. Symptoms of allergic rhinitis (AR), such as runny nose, watery eyes, itchiness and nasal congestion, and difficulty concentrating on everyday tasks, can all cause significant frustration and discomfort. They often have a negative impact on sleep quality, job performance, overall quality of life resulting in decreased productivity and increased overall medical and work/school related costs. In the school aged population, this effect from AR can interfere with learning (Vuurman EFR, van Veggel LM, Uiterwijk MM, et al. Seasonal allergic rhinitis and antihistamine effects on children's learning. Ann Allergy. 1993;71:121-126)
The recent documentation of the significant negative cognitive effect of AR brings a whole new important aspect to what has been an undocumented but frequently complained about patient symptom (especially if the physician asks!)(Wilken JA, Berkowitz R, Kane R. Decrements in vigilance and cognitive functioning associated with ragweed-induced allergic rhinitis. Ann Allergy, 2002; 89:373-380) What is also cogent to this discussion is the fact that not only can the exacerbation of the allergic rhinitis cause cognitive effect but also mood effects and the medications often used to treat AR can sometimes be a major contributor to this same effect in some of these patients. (Marshall PS, Colon EA. Effects of allergy season on mood and cognitive function. Ann Allergy. 1993; 71:251-258. SpatethJ, Klimek L. Moses R. Sedation in allergic rhinitis caused by the condition and not the antihistamine treatment. Allergy. 1996;51:893-906)
For those who seek medical care for their AR, there are many ways physicians can provide assistance, but for this added insight make sure you ask the right questions of your doctor. Patients and their families don't often associate these other cognitive or mood effects with untreated AR. Some of the medications we use to treat AR can either alleviate or exacerbate this cognitive aspect.
Antihistamines are the most suitable agents for the treatment of mild, intermittent AR. They can also be used in conjunction with other agents for patients with more severe or persistent symptoms or concomitant allergic conjunctivitis or allergic asthma. Their main function is to interfere with the effects of released mediators from the allergic reaction and in so doing thereby reduce the key symptoms of sneezing, itching and rhinorrhea. One of the most important aspects to consider when recommending an antihistamine is the issue of the significant but often unrecognized detrimental central nervous system (CNS) effects of some these agents. (Wilken et al again Ann Allergy 2002:89; 372-380, Nicholson AN, Turner C. Central effects of the antihistamine cetirizine. Aviate Space Environ Med 1998; 48:200-206. Warren R, Simpson H, Hilchie J, et al. Drugs detected in fatally injured drivers in the province of Ontario. In: GoldbergL, editor. Alcohol, Drugs, and Traffic Safety, Vol 1, Stockholm, Sweden; Almqjuist & Wiksell; 1981:1203-217. Weiler JM, Bloomfield JR, Woodworth GG, et al. Effects of fexofenadine, diphenhydramine and alcohol on driving performance. A randomized placebo-controlled trial in the Iowa-driving simulator. Ann Intern Med 2000:132:354-363.Verster, JC, Volkerts ER, Ann Allergy 2004:92:294-303, Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic.)
These agents are over the counter and the decision to purchase is often made solely by the uninformed patient. Since some of this data is so recent, all this information has to some degree not yet completely permeated all of the pharmacies and physician offices. Unfortunately these recently described detrimental side effects on cognition and performance are oftentimes not readily recognized.
Older agents like diphenhydramine and hydroxyzine cross the blood-brain barrier more readily than the newer antihistamines. (reference Verster JC Volkerts article and Weiler JM article Ann Int Med 2000) This means that at recommended doses, there is a greater risk of activity in the CNS for the older agents. The effects that have been detected in clinical trials do not necessarily correlate with subjective assessment of impairment. (Weiler JM article Ann Int Med 2000) In this study, approximately 1/3 of patients on diphenhydramine felt sedation, but all of them performed poorly as compared to the control population and the "non-sedated" ones actually got into more severe simulated accidents and had the worst reaction times. There is probably nothing worse than a person who is cognitively compromised, but doesn't recognize his/her disability and doesn't compensate for it by driving slower or taking other precautions! Unfortunately 47% of all antihistamines sold in the North American marketplace are first generation antihistamines with the most potential for significant serious adverse effects. Recently, proposed legislation was tabled in the House of Commons in Canada with the intent to make it a crime to be driving under the influence of sedating medications. If this legislation ever passes it makes this situation becomes even more important to patients and the related legal aspects to their prescribing physicians. The most well known CNS effect of antihistamines is sedation. However, the CNS story with antihistamines goes further than that. A recent clinical study compared an agent known to be associated with CNS effects (diphenhydramine 50 mg) with one that is thought to be free of such problems (desloratadine 5 mg) and with placebo8. The study involved 204 adult patients with ragweed-induced AR. They were challenged with controlled doses of ragweed in an Environmental Exposure Unit until they developed a certain degree of objective and subjective symptoms.
Study investigators performed a wide range of computerized neuropsychological tests at baseline and after randomized to either the medication or placebo to test a wide array of cognitive function measures. They found that treatment with diphenhydramine was associated with clinically meaningful decrements on all vigilance and cognitive parameters compared with desloratadine (p < 0.05).8 The Kay Continuous Performance Test measures vigilance by tracking the number of errors of omission made in a prespecified time. In this study, patients in the diphenhydramine group averaged two more errors than those in the placebo group, while those in the desloratadine group averaged one fewer error than those in the placebo group. This assessment occurred in a ten-minute interval. This could be extrapolated to potentially 12 errors per hour or 96 errors in a regular 8-hour workday. This potential for so many extra errors in the patients affected by diphenhydramine, could be very significant in a worker perhaps handling air traffic control, a pilot or bus driver or even an everyday driver in the lane next to you on the freeway. This is an issue that deserves another look by all of us when prescribing for our patients.
In this study, diphenhydramine use was also associated with significantly more somnolence compared to desloratadine or placebo. Both desloratadine and diphenhydramine were equally efficacious in relieving symptoms of AR compared to placebo.
However, it is important to realize CNS effects are not restricted to the older antihistamines. There has been evidence accumulated over the years showing cetirizine may also cause CNS effects in adults,9-19 (also Verster, JC, Volkerts ER, Ann Allergy 2004:92:294-303, Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic.) evidence that is reflected in the product labeling. Current Canadian and USA Federal guidelines for pilots suggest at least a 24-hour abstinence before flying when using cetirizine. Needless to say the effects of alcohol on these situations is generally additive. (Verster, JC, Volkerts ER, Ann Allergy).
So it's important to realize that the allergic disease state itself can effect sedation and cognition problems in susceptible patients. Antihistamines can either help alleviate or exacerbate this problem. Not all patients are affected equally but those that are may have significant impairments that could be reversible. Altering this could significantly improve their quality of life.
Editor's note: Fexofenadine (Allegra), Diphenhydramine (Benadryl), Hydroxyzine (Atarax), Desloratadine (Aerius), Cetirizine (Zyrtec or Reactine).
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from Allergy & Asthma News, Issue 3 2004