Clinical differences exist between the benzodiazepines but demonstration of such differences requires a more specialized methodology than that normally used in comparative trials. It is recommended that double-blind studies should be carried out in hospitalized patients with severe and chronic anxiety, selected according to precise criteria, and that the trials should be designed as crossover rather than as parallel group studies, with randomization of the stages and flexible dosage. A simple graphic method of representing the clinical profile of individual benzodiazepines is described and it is suggested that this could help clinicians adapt their prescribing to each patient's symptoms.

The therapeutic effect and safety of alprazolam and doxepin were studied in 126 outpatients suffering from primary unipolar depression. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with a flexible dose of 1.0-4.5 mg of alprazolam and 50-225 mg of doxepin per day. The mean final doses were 2.7 mg for alprazolam and 137.5 mg for doxepin. The results indicate that alprazolam and doxepin were equally efficacious. The incidence of side-effects was lower in the alprazolam treatment group.