A controlled long‐term study of flunitrazepam, nitrazepam and placebo, with special regard to withdrawal effects

Abstract

The hypnotic effect of flunitrazepam (Ro 5-4200), nitrazepam and a placebo was studied in 117 outpatients using hypnotics for at least 3 months prior to the study. They obtained various neurotropic drugs and this and other treatments were unchanged throughout the trial period of 13 weeks. This consisted of 3 weeks on the previously used hypnotic, 3 weeks on a test drug (during the first of these a doubling of the dose was permitted if the initial dose of 1 mg flunitrazepam, 5 mg nitrazepam or one tablet of placebo was not satisfactory) and 4 weeks' observation after a request to stop medication with the test drug. The effects were evaluated every week by self-ratings. Also noted were: the frequency of dose increase after 1 week of the test period, number of drop-outs in the test period, and failure in the attempt to stop taking the test drug. A "psychological concentration test" was done, as was a follow-up interview. The self-ratings had a good reliability and showed that more patients experienced shorter sleep induction, longer sleep time, better sleep quality and a subjective feeling of having had a better rest with flunitrazepam than with either nitrazepam or placebo. There were no differences between the nitrazepam and the placebo groups. Tiredness was the most common side effect and appeared in the same frequency in all groups. The number of patients who increased the dose after 1 week's medication, as well as the number of drop-outs, was significantly higher in the nitrazepam and placebo groups than in the flunitrazepam group. There was no difference in the ability to discontinue the medication between the test groups or between groups having previously used different hypnotics. The "psychological concentration test" did not reveal any differences between groups. It was concluded that withdrawal of a hypnotic in chronic users was not facilitated by the use of a placebo. This was interpreted as due to a strong psychological dependence upon the hypnotics and their lack of pharmacological effects during long-term treatment.

Aspectos médico-legais das substâncias utilizadas como facilitadoras de crime

“…Pode ser usado como droga recreativa também, inclusive para aumentar o efeito de outras drogas como maconha, cocaína ou álcool 27 . Tem alto potencial em causar dependência química 23 . Nos EUA pode ser encontrado em escolas, clubes ou com gangues.…”

Drug-Alcohol Interactions on Psychomotor Skills: Zopiclone and Flunitrazepam

“…Similar results have been obtained for other benzodiazepines, especially for those with long elimination half-life or with long-acting active metabolites [3,[22][23][24], and even for those with rapid elimination rate, e.g.. triazo lam and temazepam [15][16][17], provided that fairly high doses are used. There is some evi dence that glutethimide and methaqualone, unless otherwise more harmful, could be safer in this respect [22], As to zopiclone, it had not residual effects in the present study at a dose of 7.5 mg. We think that this lack of hangover, although shown in healthy volunteers, is advanta geous, as residual effects can be serious for ambulant insomniacs who are active in skilled mental or physical work despite sug gestions that in practice the residual effects of hypnotics have no major importance and that chronic insomniacs suffer from hang over similarly after nights on placebo or longacting hypnotics [6], At least results concern ing late adverse effects of hypnotics on per formance of healthy volunteers may well be generalized to a majority of patients receiving hypnotics who may not suffer from severe insomnia [10]. The comparison between pla cebo and a hypnotic with residual sequelae in patients with chronic sleeping difficulties is complicated, because such patients may ex perience 'physiological hangover' after insuf ficient sleep, namely after placebo [12].…”

Low Doses of Brotizolam and Nitrazepam as Hypnotics in the Elderly

“…Unfortunately, the long-term effi cacy of hypnotic drugs may be poor. Hartelius et al [1978] maintained that the pharmacological effect de creases after prolonged use of hypnotics and is replaced by a suggestive placebo effect. However, the present study shows significant somnifacient effects of low doses of brotizolam and nitrazepam in elderly chronic users of hypnotics.…”