Benadryl Driving Impairment Study Findings "Suspect" - W-L

Recent study results suggesting OTC cold/allergy remedy Benadryl impairs driving abilities more than alcohol are "suspect" and the study design "is seriously flawed," Warner-Lambert stated.

The study in question, conducted by University of Iowa researchers and published in the March 7 Annals of Internal Medicine, compared the effect that Benadryl (diphenhydramine 50 mg), Rx antihistamine Allegra (fexofenadine 60 mg), alcohol and placebo had on operating a motor vehicle in a simulated environment. Allegra marketer Aventis (formerly Hoechst Marion Roussel) funded the research.

Led by Iowa's John Weiler, MD, the investigators found that "after participants took diphenhydramine... driving performance was poorest, indicating that diphenhydramine had a greater impact on driving than alcohol did." Participants administered fexofenadine or placebo scored similarly in driving measurements recorded in the driving simulator.

Reacting to the conclusions, Warner-Lambert alleged there are "numerous flaws and biases in the study analysis." For example, "although the authors report a statistically significant difference for diphenhydramine vs. placebo, they neglect to report that there was no significant difference between Allegra and alcohol."

Warner-Lambert also criticized the "small" study size and the authors' decision to fill in "missing data" for eight of the simulator sessions based on a "worst-case" analysis. "In other words, they created their own data," W-L contested.

Furthermore, the Benadryl maker accused Aventis of having an inappropriate "'consulting' role in the design, conduct and reporting of the study," noting one of the authors, Thomas Baker, is an Aventis employee.

The randomized, double-blind, crossover trial involved 40 licensed drivers ages 25 to 44 with seasonal allergic rhinitis. Subjects were given a single dose of either fexofenadine 60 mg, diphenhydramine 50 mg, enough alcohol to approximate a .1% blood alcohol concentration or placebo before being asked to drive the simulator in four one-hour sessions.

In the first phase of the simulation, participants were asked to follow another vehicle at a constant safe distance. When the vehicle turned off the road the second phase began, and drivers were asked to drive "as they normally would." The first three drives finished "uneventfully," while the fourth ended with a hidden car darting out onto the road, forcing the driver to react quickly to avoid a collision.

Driver performance was measured primarily by "coherence," or participants' ability to match the speed of a lead vehicle. Secondary measures included "minimum following distance," which entails trailing at a safe distance and speed; "steering instability," which gauges lateral position within a specified lane; and "lane excursions," or the number of times a driver crosses the centerline or shoulder. Response to a blocking vehicle was recorded, as was self-reported drowsiness.

The mean coherence score after participants took diphenhydramine (.877) was statistically lower than the mean score after they consumed alcohol (.920), fexofenadine (.915), or placebo (.906).

In the secondary measures, most participants also performed worse after taking diphenhydramine or alcohol; the difference between fexofenadine and placebo was not significant, Weiler et al. report.

Commenting on the high coherence scores for the alcohol group, the authors note that "although participants under the influence of alcohol did surprisingly well at matching the velocity of the lead car, they did so at the expense of driving closer to that vehicle and having less control over steering."

Warner-Lambert asserted that the more favorable coherence scoring among the alcohol group "suggests that one should use alcohol to obtain the highest possible degree of driving competence...which seriously impugns the study conclusions."

The coherence measure "has not been validated as a true indicator of risk for motor vehicle crashes," Sean Hennessy and Brian Strom, MD, University of Pennsylvania, note in an accompanying editorial. Thus, while "existing data indicate that usual doses of sedating antihistamines impair measures of driving performance in experimental settings...the clinical significance of these impairments is unknown."

However, despite the potential problems with the study, the editorial concludes "the safest approach would be to preferentially initiate therapy with nonsedating antihistamines over sedating antihistamines in patients who drive."