RESUMEN
To evaluate the efficacy and safety of reduced doses of the benzodiazepine agonist quazepam in older insomniacs, 30 men and women > 60 years old with chronic insomnia were randomly assigned to receive 0, 7.5, or 15 mg quazepam. After two placebo nights, each subject received the appropriate dose for seven consecutive nights, which was followed by two placebo recovery nights. Both doses increased total sleep time relative to placebo during the early (nights 1 and 2) and late (nights 6 and 7) treatment phases. The low dose reduced sleep latency during the late phase, whereas the high dose reduced sleep latency in both early and late treatment phases. These observed hypnotic effects for both doses did not diminish over the seven nights of repeated administration. There also was a continued hypnotic effect during the two nights of placebo recovery for both doses. Analyses of plasma concentrations of quazepam and its metabolites suggested the continued drug effects on sleep during recovery are due to the metabolite desalkylflurazepam. In the safety evaluation done by means of adverse drug event assessments and postsleep questionnaires, the adverse events reported were minimal and not drug or dose related.
Asunto(s)
Ansiolíticos , Benzodiazepinas/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Anciano , Benzodiazepinas/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hipnóticos y Sedantes/efectos adversos , Masculino , Polisomnografía , Fases del Sueño/efectos de los fármacos , Resultado del TratamientoRESUMEN
The dose range of estazolam for hypnotic effects was studied in seven men and eight women (mean age 30.3 +/- 8.6 years) who complained of insomnia and had polysomnographic evidence of disturbed sleep. Patients slept in the laboratory and were monitored using standard polysomnographic techniques. Four consecutive nights in the laboratory with placebo, which served as baseline and screening nights, were followed by five 2-night drug administration periods separated by 5-day drug washout periods spent at home. Each of the patients received a sequence of four doses (0.25, 0.5, 1.0, and 2.0 mg) of estazolam and placebo administered according to a Latin square design and in a double-blind manner. Estazolam significantly increased total sleep time and reduced time awake during sleep in a dose-dependent manner. Sleep latency parameters were reduced systematically with increasing doses of estazolam, but these effects on sleep latency were not statistically significant. Increasing doses of estazolam had systematic and statistically significant effects on sleep stages. Subjective estimations of sleep were consistent with the polysomnographic findings bur were not statistically significant.
Asunto(s)
Ansiolíticos/administración & dosificación , Estazolam/administración & dosificación , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico , Adulto , Relación Dosis-Respuesta a Droga , Estazolam/uso terapéutico , Femenino , Humanos , Masculino , Tiempo de Reacción , Fases del Sueño/efectos de los fármacos , Factores de TiempoRESUMEN
Effects of ingestion of brotizolam (0.25 and 0.50 mg) over 1-3 days on polysomnographic measures of sleep were assessed in patients complaining of insomnia. Brotizolam reduced latency to sleep, number of awakenings and wake during sleep, and increased total sleep time. It also increased stage 2 sleep and decreased slow wave and rapid eye movement sleep. Increasing the dose from 0.25 to 0.50 mg increased hypnotic efficacy, and there was a more consistent and reliable effect. Discontinuation of brotizolam had minimal effects on sleep compared with placebo over the 3 nights after acute administration. No side-effects or disruption of daytime function was found using questionnaires and objective tests of performance.