OBJECTIVE: The authors' goal was to evaluate the relationship between
plasma concentrations of alprazolam and both treatment response and side
effects in patients with panic disorder and agoraphobia. METHOD: Ninety-six
patients with panic disorder and agoraphobia were treated at three sites in
a 6-week, fixed-dose, double-blind, placebo-controlled, dose-response study
of 2 mg/day or 6 mg/day of alprazolam. Assessments were made of panic
attacks, avoidance behavior, generalized anxiety, and global response.
Blood samples were collected throughout the study and analyzed for
alprazolam and other benzodiazepines. RESULTS: Patient compliance with the
protocol was judged to be good on the basis of plasma concentrations.
According to logistic regression analysis, the relationships between plasma
alprazolam concentration and response, as reflected by number of panic
attacks reported, phobia ratings, physicians' and patients' ratings of
global improvement, and the emergence of side effects, were significant.
However, there was no significant relationship between plasma alprazolam
concentration and the degree of generalized anxiety symptoms. CONCLUSIONS:
The authors conclude that plasma concentration of alprazolam is related to
treatment response, particularly in panic attacks. The alprazolam
concentration associated with treatment response or with emergence of a
given side effect varied widely among individuals, highlighting the
necessity for individualized dose adjustment to obtain optimal treatment
response while minimizing side effects.