Estazolam and Flurazepam: A Multicenter, Placebo‐Controlled Comparative Study in Outpatients with Insomnia

Abstract

A multicenter, double-blind placebo-controlled clinical trial was designed to compare the safety and efficacy of estazolam compared with flurazepam as hypnotics. Outpatients complaining of insomnia were randomized to receive either estazolam 2 mg, flurazepam 30 mg or placebo for 7 consecutive nights. The analysis of efficacy was based on the patients' daily assessments of sleep and the investigators' global evaluations. Adverse events which were considered by the investigator to be attributable to, or of unknown relationship to the test medication were analyzed. The patient subjective questionnaire indicated that estazolam and flurazepam significantly improved all parameters (P less than .05) as compared to placebo. A marked or moderate improvement in sleep was reported by 81% (58/72), 78% (63/81) and 36% (27/76) of estazolam, flurazepam, and placebo recipients, respectively. There were no significant differences in hypnotic effect between estazolam and flurazepam. All efficacy parameters of the investigators' global evaluation improved significantly more (P less than .05) for patients receiving estazolam or flurazepam (except quality of sleep) than for those receiving placebo. The percentage of patients reporting any adverse experience was greatest for flurazepam (72%), followed by estazolam (59%), and placebo (43%). Somnolence and hypokinesia were the most commonly reported adverse events. An analysis of the global evaluation of side effects showed that flurazepam had a significantly worse side effect profile than estazolam (P less than .05) or placebo (P = .001). Estazolam and flurazepam effectively, and comparably, relieved insomnia when administered for 7 nights in adult patients complaining of insomnia. Estazolam demonstrated a more favorable side effect profile than flurazepam.

Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia

“…Most benzodiazepines that improve both sleep onset and sleep maintenance are associated with next-day residual effects 8,9 , memory impairment [10][11][12] , and decreased cognitive/psychomotor function 13,14 . These agents also produce withdrawal effects and rebound insomnia with high-dose use.…”

0395 Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline

“…Three studies evaluated the efficacy of estazolam [152][153][154] using similar patient sleep questionnaires, but none of the data were suitable for meta-analysis. Likewise, it was not possible to evaluate these data with respect to the established clinical significance thresholds.…”

“…Sleep variables were assessed by patient questionnaire. Scharf 154 studied 243 outpatients with complaints of sleep onset or maintenance difficulty. Subjects were randomly assigned to one of three parallel groups: estazolam 2 mg, flurazepam 30 mg or placebo.…”

“…98,100,101,105,109,149,[152][153][154][161][162][163][164][165][166][167] No studies contained data adequate for meta-analysis. No meta-analysis of harms was possible.…”

“…In the cross-over design, 11 of 30 flurazepam group experienced morning drowsiness/hangover, which was reported by only 3 of 30 subjects during the flurazepam 15 mg period and 2 of 30 while taking placebo. Finally, Scharf 154 found AEs in 73% of the flurazepam 30 mg group versus 43% on placebo subjects. Somnolence was the most common event, reported by 57% of flurazepam subjects and 23% of the placebo group.…”