Drug Interaction on Psychomotor Skills Related to Driving: Diazepam and Alcohol

2015

STUDY: Linnoila, M., and M.J. Mattila: Drug Interaction on Psychomotor Skills Related to Driving: Diazepam and Alcohol. Europ. J. Clin. Pharmacol., 5:186-194. 1973.

Site: Department of Pharmacology, University of Helsinki, Helsinki, Finland.

Subjects: The four hundred volunteers (371 males, 29 females) were comprised of medical students, technical students, and cadets. A brief history was taken to exclude subjects suffering from diseases or taking drugs. (Caffeine and tobacco were not specifically mentioned as being exclusionary, but coffee and “drugs” were stated as excluded “during the tests.”) The mean age of the subjects was 22 years (S.D. = 2.8 years). The subjects were divided into 20 groups of 20 subjects each which were similar in sex, age, weight, educational level, and district of residence. Driving experience was not mentioned. Results of only 10 of the test groups are reported in this article.

Method: The research was experimental, under controlled laboratory conditions, using double-blind technique. Coding was changed daily, and 10 subjects were tested each day. Before any administration of drugs and drink, the subjects were instructed in the test procedures and apparatus by the same person in the same way. Each subject was tested 30, 90, and 150 minutes after taking capsules.

The groups tested were as follows:

No drug, no drink Zero group
Placebo + capsule + placebo drink Placebo group
Diazepam(5 mg) + placebo drink D5 group
Diazepam(10 mg) + placebo drink D10 group
Placebo capsule + alcohol(0.5 g/kg) A5 group
Placebo capsule + alcohol(0.8 g/kg) A8 group
Diazepam(5 mg) + alcohol(0.5 g/kg) D5 A5 group
Diazepam(10 mg) + alcohol(0.5 g/kg) D10 A5 group
Diazepam(5 mg) + alcohol(0.8 g/kg) D5 A8 group
Diazepam(10 mg) + alcohol(0.8 g/kg) D10 A8 group

Several parameters of measurement were employed, one being a commercially available choice reaction testing instrument. Subject reacted to three different light stimuli by pushing one or both of two foot pedals. They also had to push a button responding to a low pitched sound and not react to a higher pitched sound. The test totaled 36 stimuli normally requiring 54 seconds. Cumulative reaction time was recorded along with incorrect responses.

A commercially available coordination tester was used twice in each test, (I) at a fixed speed and (II) at an optimum speed chosen by the subject. The test was a tracking task to keep a black ball on a track by means of a steering wheel. Coordination test I lasted 30 seconds; test II lasted 30 to 80 seconds depending on the subject. A cumulative mistake percentage of total track length was calculated for I. The driving time was recorded in II.

Subjective examinations included: (a) subjects grading their own performances on scale of 1 (very good) to 5 (very bad); and (b) subject statements of what treatment they believed they had received.

In another test, blood alcohol levels were determined by ADA and Widmark methods for 20 medical students not used in tests, after they ingested 0.5 g/kg alcohol (10 students) and 0.8 g/kg (10 students). Five of both groups also took 10 mg of diazepam and the other five received placebos.

The results for all tests were adequately evaluated statistically.

Dosage: Diazepam was administered in 5-mg capsules, with lactose capsules as placebos. Alcohol, a bitters solution containing 28 percent alcohol, was blended w/v with one-third volume of water, using nonalcoholic bitters as placebo. The amounts were adjusted to 0.5 g and 0.8 g/kg, and drinks were cooled to 8° to 10° C.

Results: The zero and placebo groups estimated their performances as slightly lower than normal. Psychomotor variables of the placebo group were slightly impaired compared to the zero group. Group A5 psychomotor variables were slightly improved compared to those of the zero group, but only the reaction time at 30 minutes was statistically significant. At 30 minutes, the A8 group reaction times were also slightly shorter than those for the zero group and statistically significant. The driving times of the A8 group were longer than those for the zero group.

Subjects in the A5 group considered their performances good, but actually were found to be slightly (but not significantly) impaired, except for a moderate prolongation of driving time. No significant difference was found between the D5 and A5 groups. The D10 group believed their performance was improved and they actually were slightly improved, although driving time was prolonged at 30 and 90 minutes. No significant difference was found between the D10 and A8 groups.

The D5 A5 group showed slight impairment in coordination test I and increased driving time compared to the zero group, and they were more impaired than the A5 or A8 groups. Subjects in the D10 A5 group were more impaired than those in the A5 group. The difference was greater between the D10 A5 and A8 groups, and the D10 A5 group members were more impaired than those in the D10 group.

The D5 A8 group was more impaired than either the zero group or the A8 group. Likewise the D5 A8 group was more impaired than the D10 group. The D10 A8 group was also more impaired than the zero group or the A8 group. Comparison of D10 A8 with D10 showed greater impairment by the former group.

The discussion of these complex combinations of results indicated with diazepam alone, psychomotor test performances were somewhat improved after either 5- or long doses. Slight improvements were also noted after alcohol ingestion in the amounts given. Combinations of both drugs impaired psychomotor performance. It was also concluded (on the basis of unpublished data obtained by the authors) that alcohol accelerates the absorption of diazepam.

In a discussion of the relation of the findings to “real world” driving, the authors stated that coordination test I most strongly correlated with actual driving. Subjects in this test did not show improvement after single drug administration, and furthermore were the first to show impairment after taking drug combinations. It is likely that in “real world” driving, too, improvement does not occur after such single drug doses, and that psychomotor skills while driving would be impaired by the interaction of combined drugs, as they were in test I.

Comment: The detailed presentation and accompanying discussion indicates the complexities involved in studying the effects of alcohol and other drugs on driving, and their interactions. In this paper, minor impairments by combinations of diazepam and alcohol at modest dosages are demonstrated. Single drug effects showing improvement rather than impairment with 5- and 10-mg dosages are shown and then essentially discounted by the authors. From a medicolegal standpoint, initial studies involving obvious abuse-dosages of drugs would be of much greater value.

 

Selections from the book: “Drugs and Driving”. Robert Willette, Ph.D., editor. State-of-the art review of current research on the effects of different drugs on performance impairment, particularly on driving. National Institute on Drug Abuse Research Monograph 11. March 1977.