Desipramine and Imipramine Alone and Together with Alcohol in Relation to Driving Safety

2015

STUDY: Landauer, A.A., and G. Milner. Desipramine and Imipramine Alone and Together with Alcohol in Relation to Driving Safety. Pharmacopsychiatric Neuropsychopharmakologia, 4:265-275. 1971.

Site: Department of Psychology, University of Western Australia, and Mental Health Services of Western Australia.

Subjects: Twenty-seven medical students served as paid experimental subjects. Their mean age was 23.1 years (S.D. = 1.5), and mean weight was 73.7 kg (S.D. = 8.7).

Method: In this controlled laboratory study, the subjects were randomly divided into three groups of nine each. The three groups received either imipramine, desipramine, or placebo, the drugs being administered in tablet form, one at night before the experiment and the second on the morning of the experimental day – i.e., at a 12- to 14-hour interval. Alcohol was diluted with lime juice, syrup, and water and had to be drunk in less than 15 minutes

Subjects were required not to drink alcoholic beverages on the day before the test. On test day, after a light breakfast, a medical examination, and the second tablet dose, they were asked to complete a questionnaire rating themselves on their present state, and on anything felt or experienced since taking the first tablet. When 25 minutes had elapsed (for absorption) they were given motor skill tests in random order.

These tasks consisted of a tapping test, a dot tracking test, a pursuit rotor test, and a driving simulator test. Both the tests and methods of scoring them are described in the study by Patman et al. reviewed earlier in this report. When the test battery was completed, alcohol (or placebo) was given and then 30 minutes after stopping drinking a Breathalyzer test was administered.

The same test battery and Breathalyzer test were repeated. After having a meal and remaining under observation until appearing entirely sober, the subjects filled out a second questionnaire, rating themselves on their recent intoxication and on symptoms. A medical examination was performed and they were taken to their houses, with a warning not to drink or drive for 24 hours.

Dosage: Imipramine, desipramine, and placebo each took the form of one tablet, 0.8 mg/kg body weight. Alcohol and placebo alcohol doses were 0.8 ml/kg body weight, prepared as described above.

Results: All data except the present rotor test were scored before the drug key was known. The mean blood alcohol level attained was 0.074% w/v (S.D. = 0.009% w/v). The results were statistically evaluated by analysis of variance.

Only the first questionnaire showed any significant differences. The placebo group members rated themselves higher on having a stuffy nose and on frequency of headaches (P < 0.05).

The laboratory tests failed to show any significant impairments at the dosages given of either imipramine or desipramine and there was no evidence for interaction of these drugs with alcohol. Alcohol at 0.07% w/v blood alcohol content significantly impaired performance of most tests, but improved the “transformed scores” (see original article) of the driving simulator test.

Comment: The findings are another example of alcohol being the at impairing agent when drug dosages close to “therapeutic” quantities are taken with alcohol. This is more clearly seen in these experiments because the dose of alcohol used produced a mean blood alcohol content of 0.07%, a concentration at which most people begin to be objectively affected in the eyes of a careful observer.

The paper does not confine itself to simply reporting the hard data, but also contains useful discussion of review material on drugs and driving, the chemistry and pharmacology of tricyclic antidepressants, previous work on antidepressant-alcohol interaction, clinical trials of desipramine and imipramine, stimulant effects of antidepressants, and methodological difficulties encountered in studies of alcohol-drug interactions in humans.

 

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.