Effectiveness of bedtime dosing of benzodiazepines: a placebo-controlled comparison of halazepam and clorazepate

Abstract

The efficacy of halazepam and clorazepate were studied in a double-blind placebo-controlled trial. Sixty-four patients with symptoms of anxiety were treated single-blind with placebo for one week; at the end of the week, all patients scored 18 or higher on the Hamilton Anxiety Scale and were entered into the the double-blind phase of the study. They were randomly assigned to four weeks of treatment with halazepam (80 to 160 mg), clorazepate (15 to 30 mg), or placebo, each administered in a single dose at bedtime. Dosage was adjusted to fit patient needs. Patients were evaluated weekly using both physician and patient rating scales. At 19/20 time points, mean values for improvement from baseline on physician-rated measures of efficacy (global and relative evaluations, Hamilton Anxiety Scale and its two factors, psychic and somatic) showed statistically significant differences (P less than or equal to 0.10, two-tailed) favoring halazepam over placebo. Clorazepate was statistically better at 18/20 time points. Patient-rated measures of efficacy (global evaluations, Hopkins Self-Rating Scale), while showing more variability in response, tended in the same direction. Comparison of the halazepam and clorazepate treatment groups on the physician's rating of relative improvement after three and four weeks of treatment showed patients treated with halazepam significantly more improved than those treated with clorazepate (P less than 0.10). Similar differences in favor of halazepam were observed at the same time points on paired comparison of percent improvement from baseline in scores for physician's global assessment of psychopathology and the Hamilton Anxiety Scale. It is concluded that halazepam and clorazepate, when administered in a single bedtime dose, are safe and effective agents for the relief of anxiety. Daytime somnolence was not a problem with either drug and no serious or unexpected side effects occurred.