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

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.