Comparison of the therapeutic effect, tolerance and safety of ketazolam and diazepam administered for six months to out-patients with chronic anxiety neurosis.

Recently, it has been argued that benzodiazepines may not be safe or efficacious beyond 3 months continuous dosage. This study was designed to provide data regarding efficacy, safety, possible tolerance development, and possible withdrawal effects of administering ketazolam and diazepam for a 6-month period. Chronic anxiety patients were screened for participation according to specific inclusion and exclusion criteria. Of 139 patients, forty-four terminated prematurely for non-drug related reasons and are not included in the analysis. Of the ninety-five patients remaining, sixty-three were on ketazolam, and thirty-two on diazepam. Efficacy parameters included the Hamilton Anxiety Rating Scale, Physician's Global Impressions, Target Symptoms, Self-Rating Symptom Scale, and Patient's Global Impressions. Patients were evaluated weekly for the first month except for Week 3, and then seen bi-weekly and rated monthly. The results of the study showed that ketazolam was as efficacious as diazepam in treating anxiety and resulted in fewer side-effects. No adverse effects were noted in either group. Both benzodiazepines were safe and well-tolerated. No tolerance or withdrawal effects were noted. The average doses were ketazolam Week 4 (50.0 mg), Week 24 (66.14 mg) and diazepam Week 4 (26.33 mg) and Week 24 (33.0 mg). An increase in anxiety occurred in a significant number of patients after termination of either drug. By 2 weeks after the last dose many patients were free of anxiety and did not require further treatment. These results demonstrate that benzodiazepines are safe and efficacious for at least 6 months of continuous dosage.