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Therapeutics

Review: Loratadine and terfenadine do not cause sedation or psychomotor or cognitive effects

ACP J Club. 1997 Jul-Aug;127:10. doi:10.7326/ACPJC-1997-127-1-010


Source Citation

Adelsberg BR. Sedation and performance issues in the treatment of allergic conditions. Arch Intern Med. 1997 Mar 10;157:494-500.


Abstract

Objective

To determine the sedative (sleepiness and drowsiness), psychomotor, and cognitive effects of second-generation antihistamines (astemizole, cetirizine, loratadine, and terfenadine).

Data sources

Studies were identified with MEDLINE (1986 to 1994) using the keywords histamine H1 antagonists, psychomotor performance, sleep, astemizole, cetirizine, loratadine, and terfenadine. Bibliographies of relevant papers were also reviewed.

Study selection

Studies were selected if they examined the sedative (sleepiness and drowsiness), psychomotor (integration between cerebral and motor activity, including all tests that measure reaction times), and cognitive (concentration, memory, and learning ability) effects of second-generation antihistamines. Other inclusion criteria were studies of humans and placebo or active controlled studies.

Data extraction

Data were extracted on the type and dose of drug, study and patient characteristics, tests used to assess the effects of antihistamines, and objective and subjective measures of sedation and psychomotor and cognitive function.

Main results

In studies of patients with allergic conditions, 1 study showed that loratadine, terfenadine, and placebo had comparable rates of sedation; 2 studies showed that loratadine and placebo had similar rates of sedation; 1 study showed that loratadine had a similar rate of sedation compared with terfenadine and astemizole but less than cetirizine; and 1 large review (55 000 patients) showed that somnolence was reported by approximately 1% of patients who received loratadine, 10 mg daily. 1 large review found that cetirizine, 10- and 20-mg doses, caused a higher incidence of sedation (23% and 25%) than placebo (6%). Terfenadine and loratadine had no negative psychomotor effects. Data were too limited to show whether astemizole had psychomotor effects. Cetirizine had mixed results; 2 studies showed increased impairment of driving performance.

Allergy symptoms can decrease cognitive function. Most testing of cognitive function was done in persons who do not have allergies. Loratadine and terfenadine were shown not to impair cognitive function.

Conclusions

Loratadine and terfenadine do not seem to cause sedative or psychomotor or cognitive effects. Data are insufficient to assess the effects of astemizole on psychomotor performance or cognition. Cetirizine can be sedating and can adversely affect psychomotor performance.

Source of funding: Schering Corporation.

For article reprint: Dr. B.R. Adelsberg, Hamden Internal Medicine and Allergy Associates, 2416 Whitney Avenue, Hamden, CT 06518, USA. FAX 203-288-4641.


Commentary

Oral antihistamines are commonly used as first-line treatment for allergic rhinitis. The major advantage of first-generation H1 antagonists is low cost. The major advantage of some second-generation antihistamines is few if any sedative effects. The sedative effects of antihistamines are generally assessed in large randomized, placebo-controlled trials. Based on such studies, the antihistamines terfenadine, astemizole, loratadine, and fexofenadine are labeled as being "nonsedating."

Some antihistamines have also been studied using such standardized or quantitative methods as sleep latency, response time, driving performance, and learning ability. This review includes all such studies published from 1986 to 1994. Critical review of these published studies shows that terfenadine and loratadine produce sedation or affect psychomotor performance at a rate virtually identical to that of placebo. Cetirizine, another second-generation antihistamine, has a sedative effect and affects psychomotor performance more than placebo but less than first-generation anti-histamines. Very few studies assess the effects of astemizole on psychomotor performance, although safety and efficacy trials show a nonsedating effect.

This review provides reassurance to clinicians that terfenadine, loratadine, and probably astemizole do not cause sedation or psychomotor disturbances when prescribed in usual doses. (1 reviewed study showed that a higher dose of loratadine [40 mg] adversely affected psychomotor function). 2 newly available antihistamines were not included in the review: Azelastine nasal spray produces an intermediate sedative effect (1), whereas fexofenadine is considered nonsedating (2).

The second-generation antihistamines differ in their likelihood of producing QT prolongation and such cardiac arrhythmias as torsades de pointes. Terfenadine and astemizole may cause these cardiac effects, whereas loratadine, cetirizine, and fexofenadine do not.

Patients taking first-generation antihistamines may experience sedative effects and should not drive or operate machinery and should not consume alcohol or sedating medications. Thus, for most patients who require treatment with an H1 antagonist, a sound rationale exists for selecting a nonsedating second-generation antihistamine that does not cause QT prolongation.

James T. Li, MD
Mayo ClinicRochester, Minnesota, USA

James T. Li, MD
Mayo Clinic
Rochester, Minnesota, USA


References

1. LaForce C, Dockhorn RJ, Prenner BM, et al. Ann Allergy Asthma Immunol. 1996;76:181-8.

2. Graul A, CastaƱer J. Drugs of the Future. 1996;21:1017-21.