CLONAZEPAM IN THE TREATMENT OF PANIC DISORDER - A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL INVESTIGATING THE CORRELATION BETWEEN CLONAZEPAM CONCENTRATIONS IN PLASMA AND CLINICAL-RESPONSE

Thirty-two outpatients with a DSM-III diagnosis of panic disorder or a goraphobia with panic attacks were randomly assigned to 4 weeks of tre atment with clonazepam or placebo, after a 1-week placebo washout peri od. Twenty-nine patients entered the double-blind phase of the study a nd were eligible for intent-to-treat analysis. Clonazepam-treated pati ents experienced significantly fewer panic attacks, and these were of lesser intensity and short duration than those in placebo-treated pati ents (p < 0.001). Clonazepam was also superior to placebo with respect to symptoms of anxiety and depression (p < 0.001). The mean dose of c lonazepam at week 4 was 2.2 mg (standard deviation, 0.7 mg). There was significant (p < 0.05) correlation between drug concentration in plas ma and decrease in the global measure of the severity of panic disorde r (r = 0.68); similar trends were seen for the decreases in frequency (r = 0.60) and severity (r = 0.55) of panic attacks, but not between c oncentration in plasma and decline in generalized anxiety. The most co mmon adverse event was drowsiness, which occurred in 9 of 13 clonazepa m-treated patients.