Low doses of ketazolam in anxiety: a double-blind, placebo-controlled study

A multicenter, double-blind, between-patient trial comparing two doses of ketazolam (15 and 30 mg) with placebo, each given once daily, in the evening, to 92 outpatients affected by generalized anxiety disorders for at least 1 month, was carried out. After 1-week washout period 47 patients were randomized to ketazolam 15 mg, and 45 to placebo for 15 days (first period). At the end of this period, if the patient experienced a decrease on the total Hamilton Anxiety Rating Scale (HAM-A) of at least 25% of basal value, the treatment was kept unchanged for a further 15 days, otherwise 15 mg of ketazolam were added to the previous treatment (second period). Anxiety was rated after 2 and 4 weeks with the Italian HAM-A scale and with a 4-point scale (patient's assessment). Seventy-eight patients completed the first period and 75 the whole study. During the first period the percentage of responders was almost identical in both treatment groups, but during the second period a further slight improvement was observed in the early placebo responders, while the HAM-A score of patients on ketazolam continued to improve significantly (p less than 0.01) throughout the study. Likewise a significant (p less than 0.001) difference between treatments was observed, on the 4-point scale, in the population as a whole (end of first period) as well as in responder patients (end second period). Tolerability was good, except in 1 patient on placebo, who was withdrawn from the study because of severe headache.