Increased sensitivity to alprazolam in females with a paternal history of alcoholism.
BACKGROUND
Few studies have directly examined the effects of benzodiazepines in individuals with a family history of alcoholism, particularly women, to determine whether they are differentially sensitive to their effects.


OBJECTIVE
To determine whether females with a confirmed paternal history of alcoholism (FHP; n=14) were differentially sensitive to the mood and performance effects of alprazolam and buspirone compared with females without a first-degree family history of alcoholism (FHN; n=14).


METHODS
The acute effects of placebo, alprazolam (0.25, 0.50, 0.75 mg), and buspirone (5, 10, 15 mg) were evaluated using a double-blind, placebo-controlled outpatient design. Drug effects were assessed using performance tasks, observer ratings of drug effect, and subjective ratings of mood, drug strength, and drug liking.


RESULTS
Alprazolam impaired performance in a dose-related manner on all performance tasks for both groups of females, whereas buspirone had minimal effects on performance. The highest dose of alprazolam impaired the response to the digit symbol substitution test (DSST), digit recall, and word memory more in FHP females than in FHN females. Further, performance on the DSST and immediate word recall was able to accurately predict family history status. Correspondingly, FHP women reported greater increases in "difficulty concentrating" and "unmotivated" and greater decreases in items such as positive mood following alprazolam than FHN women. In contrast, alprazolam produced similar dose-related increases in subject-rated and observer-rated drug strength ratings in both groups of females. Lastly, there was no evidence of an increase in ratings of drug liking in either group following alprazolam.


CONCLUSIONS
In contrast to many previous findings with FHP males, these results suggest that FHP females may be more sensitive to the performance-impairing effects and negative subjective effects of alprazolam.
Evans
S M
SM
New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, NY 10032, USA. se18@columbia.edu
Levin
F R
FR
Fischman
M W
MW
D000339:Affect / Q000187:drug effects* / Q000502:physiology; D000437:Alcoholism / Q000235:genetics*; D000525:Alprazolam / Q000494:pharmacology*; D000704:Analysis of Variance; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D002065:Buspirone / Q000494:pharmacology; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005220:Fathers; D005260:Female; D006801:Humans; D008297:Male; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D011597:Psychomotor Performance / Q000187:drug effects* / Q000502:physiology
D014151:Anti-Anxiety Agents; D002065:Buspirone; D000525:Alprazolam