Brotizolam and chronic insomnia: a multi‐centre study.

Abstract

1 A double-blind, crossover study was carried out on the acceptability of three doses of brotizolam (0.125, 0.25 and 0.5 mg) in chronic insomniacs aged between 21 The patients, of whom 44 had a primary complaint of insomnia, were informed of the nature of the study and verbal consent was obtained. They were divided randomly into two groups and after a period of 3 days without medication they received therapy for a period of 4 weeks followed by 3 days of placebo ingestion. For periods of 7 days within the 4-week medication period the first group received 0.25, 0.5, 0.25 and 0.125 mg brotizolam respectively, and the second group received 0.25, 0.125, 0.25 and 0.5 mg brotizolam respectively. The medication was ingested before going to bed.The patients were seen by the physician on days 3, 10, 17 and 24 immediately before the commencement of each 7-day period of therapy, and on day 31 at the end of therapy and on day 34 at the end of the 3-day placebo period. At these times daily and nightly assessments, compliance, side-effects and overall efficacy were assessed and weekly assessments completed. The data were analysed using analysis of variance with the 3 days preceding medication as the control period.The study did not establish any consistent differences between the efficacy and side-effects of the various doses of the drug. With all doses the patients reported a shorter time to fall asleep (P < 0.001), prolonged (P < 0.001) and deeper sleep (P < 0.001), and the number of times they reported waking during the night decreased (P < 0.001). Improvement in sleep was reported during the first week of the study (0.25 mg brotizolam) in both groups (P < 0.001), and they felt more rested in the morning. There were no dose-related side-effects, and one patient withdrew from the study because of headaches. After the 4-week period of medication assessments of sleep tended to return to those of the control period.This study together with related investigations (Sinchez-Martfnez & Landa-Palos, 1982; Rodrfguez et al., 1981;Velasco et al., 1981) has demonstrated in a clinical setting the usefulness of brotizolam as an hypnotic, although it did not establish any consistent dose-related differences. However, although there was no evidence of untoward effects with the highest dose (0.5 mg), the efficacy of the lower doses, together with other experimental (Nicholson et al., 1980;Roehrs et al., 1983) and clinical Lohmann et al., 1983) studies, would suggest the dose range 0.125-0.25 mg as appropriate in the treatment of insomnia. Further, brotizolam was found to be effective over a 4-week period of ingestion, and on withdrawal there was no evidence of an adverse effect on sleep which would suggest a rebound phenomenon.413S