Differences in pharmacodynamics but not pharmacokinetics between subjects with panic disorder and healthy subjects after treatment with a single dose of alprazolam.
The pharmacokinetics and pharmacodynamics of the benzodiazepine alprazolam (1 mg, administered orally) were compared between eight patients with panic disorder and eight age- and sex-matched healthy volunteers. Subjects received orally administered placebo and alprazolam in a randomized, double-blind, single-dose crossover study. The elimination half-life, time of maximum plasma concentration, maximum concentration, volume of distribution, and clearance of alprazolam were similar for both groups. For each cohort, alprazolam treatment (vs. placebo) produced significant changes in typical benzodiazepine agonist effects, such as increased sedation and impaired cognitive performance on the digit-symbol substitution test. For the panic disorder group only, there was a significant increase in the subjective rating of"contented" and a reduction in the rating of "easily irritated." For the healthy volunteer group, alprazolam produced increases in ratings of "fatigued" and "slowed thinking," but also increases in ratings of "relaxed." In each group, alprazolam significantly increased the electroencephalographic (EEG) measure of relative beta amplitude (range, 13-30 Hz) compared with placebo. Concentration-EEG response curves fit a sigmoid E(max) model, and there was greater sensitivity to EEG effects, as measured by a 28% reduction in the EC50 value, in the panic disorder group compared with healthy control subjects. After alprazolam treatment, there was increased sensitivity to EEG and mood effects and fewer aversive effects in the panic disorder group compared with healthy subjects. There were no differences in the pharmacodynamic measures of sedation and cognition or differences in pharmacokinetics between the two groups.
Kaplan
G B
GB
Veterans Affairs Medical Center and the Department of Psychiatry and Human Behavior, Brown University School of Medicine, Providence, Rhode Island, USA.
Greenblatt
D J
DJ
Ehrenberg
B L
BL
Goddard
J E
JE
Harmatz
J S
JS
Shader
R I
RI
D000328:Adult; D000525:Alprazolam / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D016584:Panic Disorder / Q000188:drug therapy* / Q000523:psychology; D011569:Psychiatric Status Rating Scales; D013997:Time Factors
D014151:Anti-Anxiety Agents; D000525:Alprazolam